Göran Jönsson - Academia.edu (original) (raw)

Papers by Göran Jönsson

Arthritis Research & Therapy, 2013

Introduction: The objective of the study was to investigate the impact of newer biologic treatmen... more Introduction: The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA). Methods: Patients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post-and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥2. Results: In total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%. Conclusion: In this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment. Trial registration: NCT00828997 and EudraCT EU 2007-006539-29.

Scandinavian Journal of Rheumatology, Feb 6, 2015

Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients o... more Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. Method: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagnostic codes. The following infections were considered as serious cases: pneumonia, other lower respiratory infections, meningitis, sepsis, and septic arthritis. The relative risk (RR) of infection was calculated as the number of events after/number of events before vaccination. Ratios of relative risk (RRRs) were calculated between vaccinated and non-vaccinated groups of patients. A generalized estimating equation (GEE) was used to handle correlated data for several events in the same individual. Results: Although statistically non-significant, the point estimate of the RRR [0.55, 95% confidence interval (CI) 0.25-1.22] suggested a reduced risk of serious pneumococcal infections in vaccinated patients compared to the unexposed group. Conclusions: Vaccination with PCV7 tended to reduce the risk of putative serious pneumococcal infections by about 45% compared to non-vaccinated patients in this observational cohort study.

factors contribute to this discrepancy and in what RA patients CysC should be evaluated remain to... more factors contribute to this discrepancy and in what RA patients CysC should be evaluated remain to be elucidated. Objectives: To clarify the factors contributing to the discrepancy between eGFR measured using Cr (eGFR-Cr) and CysC(eGFR-CysC). Methods: We enrolled 236 RA patients (188 females, 48 males; mean age 65.3±14.0 years; disease duration 12.0 ± 11.0 years). We measured BUN, Cr, CysC, IgG, IgA, IgM, C3,C4, CH50, RF and aCCP in patient serum, urinary proteins, urinary blood, and urinary casts and evaluated CDAI, SDAI, disease activity score (DAS) 28-CRP and DAS28-ESR. Steinbrocker functional classification and radiological grading were evaluated. History of diabetes mellitus, hypertension and hyperlipidemia was determined from the medical records. Estimated glomerular filtration rate (eGFR) was calculated by the new Japanese coefficient-modified Modification of Diet in Renal disease (MDRD) study equation. Results: The eGFR-Cr and eGFR-CysC of RA patients were 72.5±20.2 (12.0~142.0) and 72.3±24.9 (6.3~167.8), with no significant difference between the two. The correlation between them was significant (r=0.715, p<0.0001). However, 26 of 180 patients with eGFR-Cr greater than or equal to 60 showed eGFR-Cys of less than 60. To clarify the factors that contribute to a greater than 20% discrepancy (eGFR-Cr !20% higher than eGFR-CysC) between eGFR-Cr and eGFR-CysC, we divided our patients into group A (eGFR-Cr/eGFR-CysC ! 1.2) and group B (eGFR-Cr/eGFR-CysC < 1.2). Group A was older (73.8±12.5 vs 63.2±13.6 years), had longer disease duration (17.7±14.0 vs 10.4±9.5 years), lower BMI (20.0±2.9 vs22.4±3.6), lower CK (63.9±36.0 vs 92.5±79.6), higher disease activity, more frequent diabetes mellitus (35.6% vs 11.0%) and more frequent stage 4 of Steinbrocker radiological grading (47.7% vs 15.3%) than Group B by univariate analysis significantly (p<0.01). We then performed multifactorial analysis using logistic regression analysis by stepwise method. Diabetes mellitus (OR 63.475, 8.394-479.990), SDAI (OR 1.088, 1.006-1.177), lower RBC counts (OR 0.753, 0.645-0.880), lower CK (OR 0.724, 0.598-0.876), no NSAIDs (OR 0.024, 0.003-0.219) and stage 4 of Steinbrocker radiological grading (OR 12.009, 2.962-48.678) were found as independent risk factors for group A. Conclusion: Renal functions of RA patients with high disease activity, diabetes mellitus, advanced stage, anemia or lower CK could be overestimated when judged using eGFR-Cr alone. Assessment of renal function in such RA patients requires particular attention. REFERENCE: [1] Nozawa Y, Sato H, Wakamatsu A, et al. Utility of estimated glomerular filtration rate using cystatin C and its interpretation in patients with rheumatoid arthritis under glucocorticoid therapy. Clin Chim Acta 2018; 487, 299-305.

Annals of the Rheumatic Diseases, Jun 1, 2014

Background: Foot and ankle problems are common but often neglected in Rheumatology patients. We d... more Background: Foot and ankle problems are common but often neglected in Rheumatology patients. We developed a self-administered, rapid screening questionnaire with unique feature of diagrams for patients to indicate their problems visually. There are ten questions which include domains of symptoms, function, disability, work, footwear and surgery. We further simplified the language (SMOG reading age <11), and added a patient global assessment 100mm VAS to allow patients to express symptom severity. Objectives: Our objective was to assess the usability of the modified Swindon Foot and Ankle Questionnaire (SFAQ) in different rheumatology units where foot screening questionnaires are not routinely used. Methods: 234 patients from 3 rheumatology centres (Swindon n=86, Truro n=87, Basingstoke n=61) were invited to complete the SFAQ prior to outpatient consultation. We recorded their rheumatological diagnosis, SFAQ score (0 to 10), VAS score (0 to 100) and recorded if they had used the foot diagrams. Results: All 234 patients completed the SFAQ, the vast majority unaided. Diagnoses included Rheumatoid Arthritis (40%), Psoriatic Arthritis (14%), Ankylosing Spondylitis, Osteoarthritis, Fibromyalgia, Sjogren's and SLE. SFAQ 10 point questionnaire score: mean 2.9, median 3.0 (range 0-10); 62 patients (26%) scored 0. VAS: 192 (82%) patients completed the 100mm VAS: mean 28, median 20, (range 0-100). There was a strong correlation between the SFAQ score and VAS foot score (r=0.67) 15 patients did not use the VAS. 27 patients wrote words above the VAS instead of a marking a line. Pictures: 146 (62%) patients indicated their symptoms on the foot diagram; 10 patients used neither diagram nor VAS and their mean SFAQ score was 0.9 (n=10). Work: 19 (8.5%) answered 'yes' to the question "in the last week have your feet or ankles stopped you going to work?" Their mean VAS score was 67 and mean SFAQ score was 7.1. Conclusions: The modified SFAQ is a rapid, patient administered questionnaire, simple enough to be completed unaided prior to consultations in different rheumatology centres. The questions, foot diagrams and VAS were all widely used and gave patients the opportunity to communicate their symptoms in a variety of ways. There was a strong correlation between SFAQ score and VAS score. 8.5% patients with high scores reported their foot and ankle symptoms had stopped them working. Clinicians may use this as a rapid tool to prompt early diagnosis and treatment of foot and ankle problems in Rheumatology patients, highlighted as a commonly neglected aspect of patient care.

Arthritis & Rheumatism, Nov 29, 2011

Objective. To study the influence of antiinflammatory treatments, including methotrexate (MTX) an... more Objective. To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. Methods. Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n ‫؍‬ 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscu-larly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays. Results. Positive antibody response was defined as an antibody response ratio (ARR) (i.e., ratio of postto prevaccination antibody levels) of >2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P ‫؍‬ 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA. Conclusion. Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses. Patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA), including psoriatic arthritis, receiving traditional disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and/or biologic agents have an increased risk of vaccine-preventable diseases, including those caused by Streptococcus pneumoniae (1-9). A standard 23-valent polysaccharide vac-ClinicalTrials.gov identifier: NCT00828997; EudraCT database no. EU 2007-006539-29.

Research Square (Research Square), Dec 16, 2021

Background: To examine rates of serious pneumococcal infections up to 10 years after vaccination ... more Background: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. Methods: In total, 595 adult arthritis patients (rheumatoid arthritis; RA=342, 80% women and spondylarthropathy; SpA=253, 45% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identi ed. At vaccination, 420 patients received bDMARDs (anti-TNF=330, tocilizumab=15, abatacept=18, anakinra=1, rituximab=56). Methotrexate was given as monotherapy (n=86) or in combination with bDMARD (n=220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to rst event and predictors of infections. Results: Among vaccinated RA and SpA patients, there was a signi cant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no signi cant difference in time to rst pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. Conclusion: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.

Scientific Reports, 2021

Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investig... more Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied. Blood samples were collected: before MTX, ≥ 4 weeks on stable MTX dose (prevaccination), and 7 days postvaccination (MTX group), and pre- and 7 days postvaccination (0DMARD and HC). Phenotypes of B- and T cell subsets were determined using flow cytometry. Serotype-specific IgG were quantified using multiplex bead assay, pre- and 4–6 weeks postvaccination. Concentrations of plasmablasts and switched memory B cells increased after PCV in HC (both p = 0.03) and the 0DMARD group (p = 0.01 and p = 0.02), but not in the MTX group. Postimmunization plasmablasts were lower in MTX group, compared to the 0DMARD g...

Arthritis Research & Therapy, 2020

Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal con... more Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. Methods Patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number...

Annals of the Rheumatic Diseases, 2016

Molecular Immunology, 2006

Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging fro... more Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging from a Swedish study of C2 deficiency, a deficiency with an estimated prevalence of about 1/20,000 in Western countries, less than 10% of the deficiencies of the classical and alternative pathways and the late complement components are identified in Sweden. C1 inhibitor deficiency and deficiencies of MBL and MASP-2 were not included in the assessment. The introduction of new screening methods should facilitate detection of complement deficiencies in clinical practice. In our study of C2 deficiency (n = 40), 57% of the patients had a history of invasive infection with encapsulated bacteria, mainly Streptococcus pneumoniae. This emphasizes the importance of the classical and/or the lectin pathway in defence against severe infection. Rheumatological disease, mainly systemic lupus erythematosus was present in 43% of the patients. In addition, a significant association was found between C2 deficiency and atherosclerosis. Complement-dependent disease mechanisms are discussed together with the potential importance of non-complement genes for disease expression in complement deficiencies. Analysis of larger patient groups is required in order to establish guidelines for investigation and treatment of patients with complement deficiency.

Rheumatology, Nov 15, 2005

Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax Õ) in contr... more Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax Õ) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. Methods. Patients with RA (n^149) and healthy controls (n^47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. Results. Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P^0.037 for 23F and P^0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. Conclusions. Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.

Human Vaccines, 2009

Aim: To study the effect of standard of care therapy on antibody response and functionality follo... more Aim: To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls. Methods: 49 patients with vasculitis and 49 controls received a single dose (0.5 ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n = 11), cyclophosphamide (CYC; n = 6), methotrexate (MTX; n = 9), rituximab (n = 3); anti-TNF (n = 2), mycophenolate mofetil (n = 2), prednisolone alone (n = 15) and no active treatment (n = 2). Specific antibody concentrations for serotypes 6B and 23F were determined using ELISA and opsonophagocytic activity (OPA) assay (23F) was performed, on serum samples taken immediately before and 4-6 weeks after vaccination. Proportion of individuals with putative protective antibody concentration (!1.0 µg/mL) and positive antibody response (!2-fold increase from prevaccination concentration) for both serotypes were calculated and groups were compared. Results: At baseline, 6 patients (12%) and 12 controls (24%) had protective antibody levels for both serotypes. After vaccination, antibodies increased for both serotypes in patients and controls (p < 0.001), 32 patients (65%) and 35 controls (71%) reached protective level for 6B, and 32 patients (65%) and 37 controls (76%) for 23 F. Compared to controls, patients had lower prevaccination geometric mean concentration (23F, p = 0.01) and a numerical trend towards lower prevaccination level (6B) and postvaccination levels (both serotypes). Patients with prednisolone alone had lower prevaccination OPA (p < 0.01) compared to controls. OPA increased after vaccination in both patients and controls (p < 0.001), but improvement was better in controls (p = 0.001). AZA, CYC or MTX, but not prednisolone alone, tended towards a lower proportion of patients reaching protective antibody levels (p = 0.06), compared to controls. Conclusions: Pneumococcal conjugate vaccine was safe and immunogenic in patients with established vasculitis. Treatment with DMARDs, mostly AZA, CYC and MTX but not systemic prednisolone may impair antibody response. Trial registration. ClinicalTrials.gov Identifier: NCT02240888. Registered

Arthritis Research & Therapy, 2020

An amendment to this paper has been published and can be accessed via the original article.

Scandinavian journal of rheumatology, Jan 6, 2015

Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients o... more Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. Method: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagno...

Arthritis and Rheumatism, 2011

Arthritis Research & Therapy, 2015

Introduction: The aim of present study is to inverstigate the association between antibody levels... more Introduction: The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. Methods: A cohort of 497 patients (RA = 248 and SpA = 249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n = 85), anti-tumour necrosis factor (anti-TNF) + MTX (n = 169), anti-TNF monotherapy (n = 158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n = 85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses. Results: Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P = 0.04) and 23 F (P = 0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections. Conclusions: Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.

Rheumatology (Oxford, England), 2015

BMC Immunology, 2014

Background: Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders ... more Background: Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders mainly characterized by increased susceptibility to infections. The aims of this study were to estimate the occurrence rate of PID in the paediatric (age ≤ 18 years) population of southern Sweden (approx. 265,000 children) and to describe their demographic, clinical and immunological characteristics. During a period of 4 years, in four paediatric speciality clinics in Skåne County in southern Sweden, children being seen for infections and fulfilling specific criteria were evaluated according to a predefined examination schedule. The initial analysis consisted of complete blood counts with analysis of lymphocyte subpopulations (T, B, NK cells), measurement of immunoglobulins (IgG, IgA, IgM, IgE and IgG subclasses), and assessment of the complement system (classical, alternative and lectin pathways). In addition, results of these immunological analyses in other children from the same area and time period were evaluated. Results: In total, 259 children (53.6% males) met the criteria and were included. The most common infection was recurrent otitis media. Immunological analyses results for about two thirds of the patients were outside age-related reference intervals. Further examination in this latter group identified 15 children with PID (9 males); 7 (2.7%) had genetically defined PID, representing 4 different diagnoses, and another 8 (3.1%) had a clinically defined PID-common variable immunodeficiency. No additional PID patient was identified from the evaluation of laboratory results in children not included in the study. The median age at diagnosis was 3.5 years (range 1-12 years). Conclusions: The occurrence rate of PID was about 4 new cases per year in this population. Several different PID diagnoses were found, and the application of specified criteria to identify PID patients was useful. In children who are prone to infection, the use of a predefined set of immunological laboratory analyses at their first examination was beneficial for early identification of patients with PID.

Arthritis Research & Therapy, 2013

Introduction: The objective of the study was to investigate the impact of newer biologic treatmen... more Introduction: The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA). Methods: Patients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post-and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥2. Results: In total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%. Conclusion: In this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment. Trial registration: NCT00828997 and EudraCT EU 2007-006539-29.

Scandinavian Journal of Rheumatology, Feb 6, 2015

Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients o... more Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. Method: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagnostic codes. The following infections were considered as serious cases: pneumonia, other lower respiratory infections, meningitis, sepsis, and septic arthritis. The relative risk (RR) of infection was calculated as the number of events after/number of events before vaccination. Ratios of relative risk (RRRs) were calculated between vaccinated and non-vaccinated groups of patients. A generalized estimating equation (GEE) was used to handle correlated data for several events in the same individual. Results: Although statistically non-significant, the point estimate of the RRR [0.55, 95% confidence interval (CI) 0.25-1.22] suggested a reduced risk of serious pneumococcal infections in vaccinated patients compared to the unexposed group. Conclusions: Vaccination with PCV7 tended to reduce the risk of putative serious pneumococcal infections by about 45% compared to non-vaccinated patients in this observational cohort study.

factors contribute to this discrepancy and in what RA patients CysC should be evaluated remain to... more factors contribute to this discrepancy and in what RA patients CysC should be evaluated remain to be elucidated. Objectives: To clarify the factors contributing to the discrepancy between eGFR measured using Cr (eGFR-Cr) and CysC(eGFR-CysC). Methods: We enrolled 236 RA patients (188 females, 48 males; mean age 65.3±14.0 years; disease duration 12.0 ± 11.0 years). We measured BUN, Cr, CysC, IgG, IgA, IgM, C3,C4, CH50, RF and aCCP in patient serum, urinary proteins, urinary blood, and urinary casts and evaluated CDAI, SDAI, disease activity score (DAS) 28-CRP and DAS28-ESR. Steinbrocker functional classification and radiological grading were evaluated. History of diabetes mellitus, hypertension and hyperlipidemia was determined from the medical records. Estimated glomerular filtration rate (eGFR) was calculated by the new Japanese coefficient-modified Modification of Diet in Renal disease (MDRD) study equation. Results: The eGFR-Cr and eGFR-CysC of RA patients were 72.5±20.2 (12.0~142.0) and 72.3±24.9 (6.3~167.8), with no significant difference between the two. The correlation between them was significant (r=0.715, p<0.0001). However, 26 of 180 patients with eGFR-Cr greater than or equal to 60 showed eGFR-Cys of less than 60. To clarify the factors that contribute to a greater than 20% discrepancy (eGFR-Cr !20% higher than eGFR-CysC) between eGFR-Cr and eGFR-CysC, we divided our patients into group A (eGFR-Cr/eGFR-CysC ! 1.2) and group B (eGFR-Cr/eGFR-CysC < 1.2). Group A was older (73.8±12.5 vs 63.2±13.6 years), had longer disease duration (17.7±14.0 vs 10.4±9.5 years), lower BMI (20.0±2.9 vs22.4±3.6), lower CK (63.9±36.0 vs 92.5±79.6), higher disease activity, more frequent diabetes mellitus (35.6% vs 11.0%) and more frequent stage 4 of Steinbrocker radiological grading (47.7% vs 15.3%) than Group B by univariate analysis significantly (p<0.01). We then performed multifactorial analysis using logistic regression analysis by stepwise method. Diabetes mellitus (OR 63.475, 8.394-479.990), SDAI (OR 1.088, 1.006-1.177), lower RBC counts (OR 0.753, 0.645-0.880), lower CK (OR 0.724, 0.598-0.876), no NSAIDs (OR 0.024, 0.003-0.219) and stage 4 of Steinbrocker radiological grading (OR 12.009, 2.962-48.678) were found as independent risk factors for group A. Conclusion: Renal functions of RA patients with high disease activity, diabetes mellitus, advanced stage, anemia or lower CK could be overestimated when judged using eGFR-Cr alone. Assessment of renal function in such RA patients requires particular attention. REFERENCE: [1] Nozawa Y, Sato H, Wakamatsu A, et al. Utility of estimated glomerular filtration rate using cystatin C and its interpretation in patients with rheumatoid arthritis under glucocorticoid therapy. Clin Chim Acta 2018; 487, 299-305.

Annals of the Rheumatic Diseases, Jun 1, 2014

Background: Foot and ankle problems are common but often neglected in Rheumatology patients. We d... more Background: Foot and ankle problems are common but often neglected in Rheumatology patients. We developed a self-administered, rapid screening questionnaire with unique feature of diagrams for patients to indicate their problems visually. There are ten questions which include domains of symptoms, function, disability, work, footwear and surgery. We further simplified the language (SMOG reading age <11), and added a patient global assessment 100mm VAS to allow patients to express symptom severity. Objectives: Our objective was to assess the usability of the modified Swindon Foot and Ankle Questionnaire (SFAQ) in different rheumatology units where foot screening questionnaires are not routinely used. Methods: 234 patients from 3 rheumatology centres (Swindon n=86, Truro n=87, Basingstoke n=61) were invited to complete the SFAQ prior to outpatient consultation. We recorded their rheumatological diagnosis, SFAQ score (0 to 10), VAS score (0 to 100) and recorded if they had used the foot diagrams. Results: All 234 patients completed the SFAQ, the vast majority unaided. Diagnoses included Rheumatoid Arthritis (40%), Psoriatic Arthritis (14%), Ankylosing Spondylitis, Osteoarthritis, Fibromyalgia, Sjogren's and SLE. SFAQ 10 point questionnaire score: mean 2.9, median 3.0 (range 0-10); 62 patients (26%) scored 0. VAS: 192 (82%) patients completed the 100mm VAS: mean 28, median 20, (range 0-100). There was a strong correlation between the SFAQ score and VAS foot score (r=0.67) 15 patients did not use the VAS. 27 patients wrote words above the VAS instead of a marking a line. Pictures: 146 (62%) patients indicated their symptoms on the foot diagram; 10 patients used neither diagram nor VAS and their mean SFAQ score was 0.9 (n=10). Work: 19 (8.5%) answered 'yes' to the question "in the last week have your feet or ankles stopped you going to work?" Their mean VAS score was 67 and mean SFAQ score was 7.1. Conclusions: The modified SFAQ is a rapid, patient administered questionnaire, simple enough to be completed unaided prior to consultations in different rheumatology centres. The questions, foot diagrams and VAS were all widely used and gave patients the opportunity to communicate their symptoms in a variety of ways. There was a strong correlation between SFAQ score and VAS score. 8.5% patients with high scores reported their foot and ankle symptoms had stopped them working. Clinicians may use this as a rapid tool to prompt early diagnosis and treatment of foot and ankle problems in Rheumatology patients, highlighted as a commonly neglected aspect of patient care.

Arthritis & Rheumatism, Nov 29, 2011

Objective. To study the influence of antiinflammatory treatments, including methotrexate (MTX) an... more Objective. To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. Methods. Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n ‫؍‬ 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscu-larly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays. Results. Positive antibody response was defined as an antibody response ratio (ARR) (i.e., ratio of postto prevaccination antibody levels) of >2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P ‫؍‬ 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA. Conclusion. Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses. Patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA), including psoriatic arthritis, receiving traditional disease-modifying antirheumatic drugs (DMARDs), corticosteroids, and/or biologic agents have an increased risk of vaccine-preventable diseases, including those caused by Streptococcus pneumoniae (1-9). A standard 23-valent polysaccharide vac-ClinicalTrials.gov identifier: NCT00828997; EudraCT database no. EU 2007-006539-29.

Research Square (Research Square), Dec 16, 2021

Background: To examine rates of serious pneumococcal infections up to 10 years after vaccination ... more Background: To examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients. Methods: In total, 595 adult arthritis patients (rheumatoid arthritis; RA=342, 80% women and spondylarthropathy; SpA=253, 45% women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identi ed. At vaccination, 420 patients received bDMARDs (anti-TNF=330, tocilizumab=15, abatacept=18, anakinra=1, rituximab=56). Methotrexate was given as monotherapy (n=86) or in combination with bDMARD (n=220). 89 SpA patients received NSAIDs without DMARD. The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to rst event and predictors of infections. Results: Among vaccinated RA and SpA patients, there was a signi cant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no signi cant difference in time to rst pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections. Conclusion: One dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.

Scientific Reports, 2021

Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investig... more Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied. Blood samples were collected: before MTX, ≥ 4 weeks on stable MTX dose (prevaccination), and 7 days postvaccination (MTX group), and pre- and 7 days postvaccination (0DMARD and HC). Phenotypes of B- and T cell subsets were determined using flow cytometry. Serotype-specific IgG were quantified using multiplex bead assay, pre- and 4–6 weeks postvaccination. Concentrations of plasmablasts and switched memory B cells increased after PCV in HC (both p = 0.03) and the 0DMARD group (p = 0.01 and p = 0.02), but not in the MTX group. Postimmunization plasmablasts were lower in MTX group, compared to the 0DMARD g...

Arthritis Research & Therapy, 2020

Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal con... more Objective To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls. Methods Patients receiving rituximab (n = 30), abatacept (n = 23), monotherapy with conventional disease-modifying antirheumatic drugs (cDMARDs, methotrexate/azathioprine/mycophenolate mofetil, n = 27), and controls (n = 28) were immunized with a dose PCV followed by PPV23 after ≥ 8 weeks. Specific antibodies to 12 serotypes included in both vaccines were determined using a multiplex microsphere immunoassay in blood samples before and 4–8 weeks after each vaccination. Positive antibody response was defined as ≥ 2-fold increase from pre- to postvaccination serotype-specific IgG concentration and putative protective level as IgG ≥ 1.3 μg/mL. The number...

Annals of the Rheumatic Diseases, 2016

Molecular Immunology, 2006

Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging fro... more Complement deficiencies are probably vastly under-diagnosed within clinical medicine. Judging from a Swedish study of C2 deficiency, a deficiency with an estimated prevalence of about 1/20,000 in Western countries, less than 10% of the deficiencies of the classical and alternative pathways and the late complement components are identified in Sweden. C1 inhibitor deficiency and deficiencies of MBL and MASP-2 were not included in the assessment. The introduction of new screening methods should facilitate detection of complement deficiencies in clinical practice. In our study of C2 deficiency (n = 40), 57% of the patients had a history of invasive infection with encapsulated bacteria, mainly Streptococcus pneumoniae. This emphasizes the importance of the classical and/or the lectin pathway in defence against severe infection. Rheumatological disease, mainly systemic lupus erythematosus was present in 43% of the patients. In addition, a significant association was found between C2 deficiency and atherosclerosis. Complement-dependent disease mechanisms are discussed together with the potential importance of non-complement genes for disease expression in complement deficiencies. Analysis of larger patient groups is required in order to establish guidelines for investigation and treatment of patients with complement deficiency.

Rheumatology, Nov 15, 2005

Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax Õ) in contr... more Objective. To compare antibody responses to 23-valent pneumococcal vaccine (Pneumovax Õ) in controls and patients with established rheumatoid arthritis (RA) treated with TNF blockers, methotrexate (MTX) or a combination of both. Methods. Patients with RA (n^149) and healthy controls (n^47) were vaccinated. Treatment with TNF blockers (etanercept or infliximab) and MTX was given to 50 patients, and 62 patients were treated with TNF blockers alone or with other DMARDs. MTX alone was given to 37 patients. Concentrations of immunoglobulin G (IgG) antibodies against pneumococcal capsular polysaccharides 23F and 6B were measured by enzyme-linked immunoassay before and 4-6 weeks after vaccination. An immune response was defined as a twofold or higher increase in antibody concentration following vaccination. Results. Prevaccination antibody levels for both 23F and 6B were similar in the patient groups. Antibody concentrations after vaccination increased significantly in all groups. Patients treated with TNF blockers without MTX showed better immune responses than those treated with TNF blockers in combination with MTX (P^0.037 for 23F and P^0.004 for 6B) or MTX alone (P<0.001 for both 23F and 6B). RA patients given MTX alone had the lowest immune responses. Prednisolone treatment did not influence the responses. Conclusions. Patients treated with TNF blockers and controls showed similar responses to vaccination. In contrast, patients treated with MTX had reduced responses regardless of anti-TNF treatment. The findings do not argue against the use of pneumococcal vaccination in RA patients undergoing treatment with TNF blockers.

Human Vaccines, 2009

Aim: To study the effect of standard of care therapy on antibody response and functionality follo... more Aim: To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls. Methods: 49 patients with vasculitis and 49 controls received a single dose (0.5 ml) PCV13 intramuscularly. Ongoing treatments: azathioprine (AZA; n = 11), cyclophosphamide (CYC; n = 6), methotrexate (MTX; n = 9), rituximab (n = 3); anti-TNF (n = 2), mycophenolate mofetil (n = 2), prednisolone alone (n = 15) and no active treatment (n = 2). Specific antibody concentrations for serotypes 6B and 23F were determined using ELISA and opsonophagocytic activity (OPA) assay (23F) was performed, on serum samples taken immediately before and 4-6 weeks after vaccination. Proportion of individuals with putative protective antibody concentration (!1.0 µg/mL) and positive antibody response (!2-fold increase from prevaccination concentration) for both serotypes were calculated and groups were compared. Results: At baseline, 6 patients (12%) and 12 controls (24%) had protective antibody levels for both serotypes. After vaccination, antibodies increased for both serotypes in patients and controls (p < 0.001), 32 patients (65%) and 35 controls (71%) reached protective level for 6B, and 32 patients (65%) and 37 controls (76%) for 23 F. Compared to controls, patients had lower prevaccination geometric mean concentration (23F, p = 0.01) and a numerical trend towards lower prevaccination level (6B) and postvaccination levels (both serotypes). Patients with prednisolone alone had lower prevaccination OPA (p < 0.01) compared to controls. OPA increased after vaccination in both patients and controls (p < 0.001), but improvement was better in controls (p = 0.001). AZA, CYC or MTX, but not prednisolone alone, tended towards a lower proportion of patients reaching protective antibody levels (p = 0.06), compared to controls. Conclusions: Pneumococcal conjugate vaccine was safe and immunogenic in patients with established vasculitis. Treatment with DMARDs, mostly AZA, CYC and MTX but not systemic prednisolone may impair antibody response. Trial registration. ClinicalTrials.gov Identifier: NCT02240888. Registered

Arthritis Research & Therapy, 2020

An amendment to this paper has been published and can be accessed via the original article.

Scandinavian journal of rheumatology, Jan 6, 2015

Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients o... more Objectives: To examine the risk of putative pneumococcal infections in adult arthritis patients on different anti-rheumatic drugs immunized with heptavalent pneumococcal conjugate vaccine (Prevenar 7; PCV7) and non-vaccinated individually matched arthritis patients. Method: All individuals in a cohort of 505 patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) receiving different anti-rheumatic treatments were immunized with a single dose of PCV7 (exposed group). Of these, 497 patients (RA = 248; SpA = 249) were included. For each vaccinated patient, we identified four reference subjects (n = 1988) from the same geographic area, individually matched for age, gender, and diagnosis. These were considered unexposed to conjugated pneumococcal vaccination. The Skåne Healthcare Register (SHR) was searched for all individuals seeking health care for putative pneumococcal infections occurring 4 years before vaccination and up to 4.5 years after vaccination using ICD-10 diagno...

Arthritis and Rheumatism, 2011

Arthritis Research & Therapy, 2015

Introduction: The aim of present study is to inverstigate the association between antibody levels... more Introduction: The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients. Methods: A cohort of 497 patients (RA = 248 and SpA = 249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n = 85), anti-tumour necrosis factor (anti-TNF) + MTX (n = 169), anti-TNF monotherapy (n = 158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n = 85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses. Results: Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P = 0.04) and 23 F (P = 0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections. Conclusions: Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.

Rheumatology (Oxford, England), 2015

BMC Immunology, 2014

Background: Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders ... more Background: Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of disorders mainly characterized by increased susceptibility to infections. The aims of this study were to estimate the occurrence rate of PID in the paediatric (age ≤ 18 years) population of southern Sweden (approx. 265,000 children) and to describe their demographic, clinical and immunological characteristics. During a period of 4 years, in four paediatric speciality clinics in Skåne County in southern Sweden, children being seen for infections and fulfilling specific criteria were evaluated according to a predefined examination schedule. The initial analysis consisted of complete blood counts with analysis of lymphocyte subpopulations (T, B, NK cells), measurement of immunoglobulins (IgG, IgA, IgM, IgE and IgG subclasses), and assessment of the complement system (classical, alternative and lectin pathways). In addition, results of these immunological analyses in other children from the same area and time period were evaluated. Results: In total, 259 children (53.6% males) met the criteria and were included. The most common infection was recurrent otitis media. Immunological analyses results for about two thirds of the patients were outside age-related reference intervals. Further examination in this latter group identified 15 children with PID (9 males); 7 (2.7%) had genetically defined PID, representing 4 different diagnoses, and another 8 (3.1%) had a clinically defined PID-common variable immunodeficiency. No additional PID patient was identified from the evaluation of laboratory results in children not included in the study. The median age at diagnosis was 3.5 years (range 1-12 years). Conclusions: The occurrence rate of PID was about 4 new cases per year in this population. Several different PID diagnoses were found, and the application of specified criteria to identify PID patients was useful. In children who are prone to infection, the use of a predefined set of immunological laboratory analyses at their first examination was beneficial for early identification of patients with PID.