Maria Trachana | Aristotle University of Thessaloniki (original) (raw)

Papers by Maria Trachana

Annals of the Rheumatic Diseases, Sep 1, 2000

60649 and 30 other Pediatric Rheumatology Centers One of the challenges of paediatric rheumatolog... more 60649 and 30 other Pediatric Rheumatology Centers One of the challenges of paediatric rheumatology is the diagnosis of children with ALL who are referred as possible JIA. We used an internet questionnaire in a retrospective case-control study to obtain predictive factors in 62 children with ALL and 120 children with JIA from 31 international centres. Data analysis was performed using two sided Pearson 2 or Fisher's exact tests. Results-Table 5 shows the results obtained. Using multivariate analysis and regression modelling, we evaluated further several predictive models for ALL. The best were: (a) two of three factors present (1/3 haematological values low, raised lactate dehydrogenase (LDH), night time pain; sensitivity 76%, specificity 86%); (b) blasts + 2 of 3 criteria (1/3 haematological values low, raised LDH, night time pain; sensitivity 81%, specificity 86%). These two models, as well as night time pain and raised LDH, and abnormal x rays by themselves, may be useful in diVerentiating a child with leukaemia from a child with JIA and indicating the need for a bone marrow examination. 7.26 ANA detection by recombinant antigens in juvenile idiopathic arthritis and connectivitis

Mediterranean Journal of Rheumatology, 2020

Background: The programmed cell death protein-1 (PD-1) and its ligands (PD-L 1 and 2) suppress im... more Background: The programmed cell death protein-1 (PD-1) and its ligands (PD-L 1 and 2) suppress immune responses, thus promoting self-tolerance. Among the immunomodulatory cells, acting through the PD-1 pathway, are the B-regulatory cells (Bregs). The role of the PD-1 pathway in Juvenile Idiopathic Arthritis (JIA) has not been adequately studied. Aims of the study: To investigate the immunophenotypic profile of T-and B-cells and the activity of the PD-1 pathway in JIA patients. More specifically, we will examine the levels of: a) the soluble form of PD-1 (sPD-1), b) Bregs; and the expression levels of: c) PD-1 on CD4+ and CD8+ T-cells, d) PD-L1 on Bregs and CD19+ B-cells, in blood and synovial fluid samples, at various stages of the disease (onset, relapse, remission, on or off treatment). The above biomarkers will be investigated for correlation with JIA activity. Methods: A case-control study of JIA patients (expected number: 60) and healthy controls (n: 20). Total expected number of samples: 100 of peripheral blood, 120 of serum (solely for soluble markers) and 60 of synovial fluid. The patients' demographic data and treatment will be recorded. JIA will be classified according to the ILAR and the recently proposed PReS/PRINTO criteria. JIA activity will be assessed using the JADAS-10 tool. The biomarkers will be determined using multiparametric-polychromatic flow cytometry (quintuple fluorescence protocol) and immunoenzymatic assay ELISA. Anticipated benefits: Further elucidation of the immunophenotypic expression and variation of the abovementioned molecules and cells during active inflammation and remission in JIA. Thereby, the present

Rheumatology International, 2018

To assess longitudinally the course and outcome of juvenile idiopathic arthritis (JIA) in patient... more To assess longitudinally the course and outcome of juvenile idiopathic arthritis (JIA) in patients diagnosed and followed-up exclusively in the biologic era; also, to define possible predictors of the disease progression and need for early implementation of biologicals. Prospective and retrospective, monocentric cohort study of 120 JIA patients, diagnosed between 2001 and 2010, and followed-up for ≥ 4 years (median 8.04). Disease activity, cumulative articular/extra-articular damage and quality of life were evaluated by the assessment tools Juvenile Arthritis Disease Activity Score (JADAS71), Juvenile Arthritis Damage Index (JADI) and Childhood Health Assessment Questionnaire (CHAQ), respectively. Moreover, potential predictors of the disease progression and their relation to biologic therapy were investigated. High JADAS71 score (> 9) at diagnosis was indicative of progression to polyarticular course and the need for early introduction of biologic treatment. Other independent predictors of progression to polyarthritis, were: involvement of upper limb, hip and ankle within 6 months following JIA diagnosis and percentage of cumulative time with active disease > 35% within the first year. At the end of the study, both the median JADAS71 score and the Disability Index were significantly lower than the initial (p < 0.001) and remission off medication was achieved in 25% of the patients. Articular and extra-articular (only ocular) cumulative damage was demonstrated only in 5 and 7.5% of patients, respectively. Physical functional ability was found normal/mildly restricted in 93.3% and moderately restricted in 6.7% of the patients. We believe that these findings, fit in with a picture of JIA course and outcome under current conditions of objective "disease status" evaluation and of tightly controlled follow-up. Predictors emerged from our study could contribute to the identification of patients who will need early implementation of biologic treatment.

Paediatric rheumatology, 2018

Background: Therapy of oligoarticular JIA is based on intrarticular injections of steroids, metho... more Background: Therapy of oligoarticular JIA is based on intrarticular injections of steroids, methotrexate and biotechnological therapy. ANAs-positive oligoarticular JIA patients with an early onset of disease have a consistent risk to develop uveites. Objectives: The primary aim of this study is to evaluate longitudinally the effect of non-systemic therapy and of systemic immmunomodulating drugs (e.g MTX) on ANAs in JIA patients; secondary occurance of iridocyclitis was evaluated. Methods: Monocentric retrospective not randomised study of 40 patients affected by oligoarticular JIA (ILAR classification) with ANA positivity at the baseline (T0, time of diagnosis). Patient of Group 1 received only intra-articular infiltrations or NSAID. Patients of Group 2 were treated with DMARDs (most of them with subcutaneous MTX 15 mg/m2/week) or MTX +biotechnlogical therapies. The assay for ANAs (I.I.F.) was assessed in all patients at T0, at T1 (12 months) and T2 (24 months). At 24 months was also recorded the occurence of uveitis during the follow up. Exclusion criteria were the ANAs negativity at T0 and other subgroups of JIA. Results: Twenty-one patients (52,5%) were treated with non-systemic therapy (Group 1), and ninenteen (47,5%) with systemic immunomodulating therapy (Group 2). In Group 2 fifteen subjects were treated with MTX, one with MTX plus cyclosporine, one with only cyclosporine, two with MTX plus biotechnological agent (etarnecept and adalimumab). At T1, in Group 1 only one patient out of 20 (4,8%) became ANAs negative versus 42,1% (8/19) of patients in Group 2 (p 0.0033). At T2 the incidence of ANAs positivity did not change in Group 1 (only 1/ 21 ANAs negative), while 42,1% of patients treated with systemic therapies were ANA negative (p 0.006). Three patients were lost at the follow up. The two patients who received bDMARDs in addition to MTX remained ANAs-positive both in T1 and T2. At the end of follow-up period eight uveitis have occured, six in ANAs positive patients of Group 1 (6/21, 28,5%) and two in ANA negatives patients in Group 2 (2/19, 10,5%). Conclusions: ANAs-positive patients treated with methotrexate seems to have higher possibility to became ANAs-negative versus patients treated with non-systemic immunomodulating therapy. It's known that MTX might prevent onset of uveitis in JIA, as shown in our results. Demostrating a negativization of antinuclear antibodies using MTX therapy could help to add a role of this drug in the disease history of the oligoarthritis.

World journal of pediatrics : WJP, Jan 22, 2017

To evaluate the performance of the Quantiferon(®)-TB Gold In-Tube (QFT-IT) interferon (IFN)-γ ass... more To evaluate the performance of the Quantiferon(®)-TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Agreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay...

Clinical and Experimental Immunology, 2017

Summary The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will faci... more Summary The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non-invasive diagnosis, follow-up and more appropriate use of treatment. The aim of this study was to explore the role of serum high-mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti-NCS), complement factor C1q (anti-C1q) and glomerular basement membrane (anti-GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme-linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti-NCS, anti-GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without rena...

Journal of Clinical Immunology

Pediatric Rheumatology, 2014

Kanakoudi-Tsakalidou et al.: B lymphocyte stimulator, interferon-α and HMGB 1 interrelation in ch... more Kanakoudi-Tsakalidou et al.: B lymphocyte stimulator, interferon-α and HMGB 1 interrelation in childhood onset systemic lupus erythematosus: associations with disease activity and severity.

Clinical and experimental rheumatology

Assessment of the post-etanercept (ET) disease course in patients with juvenile idiopathic arthri... more Assessment of the post-etanercept (ET) disease course in patients with juvenile idiopathic arthritis (JIA) who discontinued the drug due to disease remission, using a recently developed tool that scores the disease activity. Eleven patients (F/M 9/2, median age 9.2 years), with either a polyarthritis' (9) or an oligoarthritis' (2) disease course were followed up for 12.25-27 months after ET withdrawal. The median treatment period under ET was 36 months. The Juvenile Arthritis Disease Activity Score (JADAS) was used to grade the JIA activity at the time of ET commencement, at discontinuation and at the time of the flare. All 11 patients flared during the follow-up period. Compared to the time of ET initiation, JADAS was significantly reduced at ET discontinuation as well as at the time of the flare (26.3 to 0 and to 9.5 respectively, p<0.001). The median remission following ET discontinuation lasted 3 months. The flares were controlled with methotrexate±cyclosporine A in 1...

Clinical and experimental rheumatology

To study the immunogenicity, safety and efficacy of influenza vaccine in children with chronic rh... more To study the immunogenicity, safety and efficacy of influenza vaccine in children with chronic rheumatic diseases (CRD) receiving long-term immunosuppressive therapy. Seventy children (F:M 51:19) with CRD (JIA = 49, SLE = 11, other = 10) aged 4-17 yrs and 5 healthy siblings of the patients (aged < 11 yrs) received a "split type" influenza vaccine (Fluarix SB) licensed for the 1999-2000 winter season. Clinical and laboratory evaluation were performed at study entry and at 1, 3 and 6 months after vaccination. Blood samples were collected before and one month after vaccination and antibody titers to A/Beijing, A/Sydney and B/Beijing influenza antigens were measured using a standardized hemagglutination inhibition assay. Patients were assigned to groups according to the therapeutic regimen [prednisone (PDN), PDN plus 1 disease modifying antirheumatic drug (DMARD), PDN plus 2 DMARDs and 1 or 2 DMARDs without PDN]. 5/70 patients reported local (3) or systemic (2) reactions an...

Vaccine, 2010

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valen... more Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 ± 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p < 0.0001) in both groups and were found to be protective (>0.35 g/ml) in 87-100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p < 0.05). A ≥4-fold increase of the baseline titers to ≥5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares.

Scandinavian Journal of Rheumatology, 2010

To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile i... more To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile idiopathic arthritis (JIA). Twenty-six patients were enrolled from January 2004 to January 2008 in this prospective observational study. Inclusion criteria were either unresponsiveness to disease-modifying anti-rheumatic drugs (DMARDs; n = 17) or to other anti-tumour necrosis factor (anti-TNF) agents (n = 9) or development of uveitis under other anti-TNFs (n = 2 of the 9). Efficacy was estimated using the American College of Rheumatology Pediatric (ACR Pedi) criteria. After 1-5 years of AD exposure, nine different adverse events (AEs) were recorded (12.6 AEs/100 patient-years), mainly mild respiratory tract infections and injection site-related reactions. Serious AEs (SAEs, 2.8/100 patient-years) were the development of abscess at the site of injection (n = 1) and lethal sepsis (n = 1). The ACR Pedi ≥ 30 responses for the first to the fifth year of treatment were 88.5, 57.7, 50.0, 34.6, and 11.5%, respectively. In total, 17 of the 26 (65.4%) patients responded to AD. Five of the 11 patients under steroids discontinued them 6 months post-treatment. Seven patients required weekly AD treatment to maintain remission and four of them benefited from this policy. Recurrent uveitis was hindered in three of the six patients, no new cases were recorded, and radiological regression was observed in two of the four patients with lesions. AD was safe and efficacious during the study period in the majority of patients. However, vigilance is required for the early detection of severe and potentially fatal infections. AD may control recurrent uveitis and radiological progression.

Pediatric Rheumatology, 2008

To evaluate the 5-yr use of 2 anti-TNF preparations, Etanercept (ET) and Adalimumab (AD), in chil... more To evaluate the 5-yr use of 2 anti-TNF preparations, Etanercept (ET) and Adalimumab (AD), in children with refractory to conventional treament JIA.

Pediatric Rheumatology, 2011

Pediatric Rheumatology, 2011

Pediatric Rheumatology, 2008

Recent data in adult Rheumatoid Arthritis support that the Th17 cell-derived cytokine interleukin... more Recent data in adult Rheumatoid Arthritis support that the Th17 cell-derived cytokine interleukin 17 (IL-17) in the presence of IL-6 and IL-23 plays a critical role in the pathogenesis of chronic destructive arthritis. Data on synovial fluid (SF) concentrations of IL-17 in JIA pts are sparse. We measured concentrations of the above 3 cytokines and assessed the CD4+CD25 high FoxP3+ (Treg) and CD4+CD25 low FoxP3-T cell subpopulations in the SF of children with JIA. Findings were correlated with SF sRANKL which expresses the osteoclastic activity in active disease.

Pediatric Blood & Cancer, 2008

To the Editor: Osteonecrosis (ON) of the femoral head has been described in patients with sickle ... more To the Editor: Osteonecrosis (ON) of the femoral head has been described in patients with sickle cell disease [1], malignancies [2] and juvenile idiopathic arthritis (JIA) receiving prednisone (PDN) [3]. We present a 15-year-oldale with a systemic JIA onset, who developed secondary ON mimicking ‘‘skip’’ lesions of bone malignancy due to its unusual location in the lower part of her right thigh. Fourteen months following diagnosis, while in disease remission, she complained of a persistent femur pain. It was a continuous dull pain, with no history of trauma, aggravated by the routine physical activities, resolving with rest and responding to analgesics. Her previous regimen included methotrexate (MTX) 15 mg/m/week, cysclosporine (CSA) 3 mg/kg/day and PDN 2 mg/ kg for the first 2 months, following tapering that ended to 0.25 mg/ kg/day for the last 5 months. X-rays and MRI revealed lesions in the right femoral diaphysis and distal metaphysis suspicious of an osteosarcoma (Fig. 1). The double phase scan TI-201 did not show any radiotracer uptake and was felt to exclude malignancy. To make a definitive diagnosis, an open biopsy was performed. The specimen consisted of pieces of lamellar bone, woven bone, striated muscle and necrotic material. It was compatible either with a healing bone fracture and/or ON. She was conservatively managed by gradual withdrawal of PDN, restriction of weight bearing; she returned to her regular activities 2 months later. After a 5-year follow-up, her radiographs and MRI showed healing sclerotic lesions of the ON area with no bone marrow oedema or periosteal reaction or any soft tissue mass. ON of the femoral bone in patients with pediatric rheumatic diseases receiving long-term PDN is unusual [4,5]. We assume that PDN was the exclusive contributor to the development of ON, as data on the association of MTX or CSA with ON have not been reported. The femoral head is the most common and clinically significant site of ON, while the femoral shaft of JIA patients has not previously been reported. In adults using steroids or following radiation, insufficient fractures of the sacrum have been misdiagnosed as malignancies [6]. On the other hand, Fujimoto et al. [7] emphasized that a metastatic femur tumor can mimic spontaneous ON and have a misleading appearance on MRI imaging. We were faced with the same dilemma due to the unusual location of the ON lesions and the misleading imaging that was consistent with that of a bone tumor. Thallium scintigraphy was an important piece of data as it appeared inconsistent with malignancy [8]. However, a biopsy might be necessary to support such a diagnosis of ON, as occurred in our patient. This case highlights the importance of including ON in the differential diagnosis for bone pain of any patient receiving steroids.

Mycoses, 2001

We report the ®rst case of hepatitis due to Aspergillus terreus in a 13-year-old boy with common ... more We report the ®rst case of hepatitis due to Aspergillus terreus in a 13-year-old boy with common variable immunode®ciency that occurred while the patient was receiving secondary prophylaxis with¯uconazole after an episode of pulmonary candidosis. The infection subsided after the addition of itraconazole to the combination of liposomal amphotericin B and granulocyte-macrophage colony-stimulating factor that he was receiving. Zusammenfassung. Es wird zum ersten Mal u È ber eine Hepatitis berichtet, bedingt durch Aspergillus terreus, bei einem 13-ja Èhrigen Jungen mit Immunde®zienz wa Èhrend der sekunda Èren Fluconazol-Prophylaxe nach Lungen-Candidose. Die Aspergillose ging zuru È ck nach Applikation von liposomalem Amphotericin B, kombiniert mit Itraconazol und Granulozyten-Makrophagen-Kolonie-stimulierendem Faktor.

Annals of the Rheumatic Diseases, Sep 1, 2000

60649 and 30 other Pediatric Rheumatology Centers One of the challenges of paediatric rheumatolog... more 60649 and 30 other Pediatric Rheumatology Centers One of the challenges of paediatric rheumatology is the diagnosis of children with ALL who are referred as possible JIA. We used an internet questionnaire in a retrospective case-control study to obtain predictive factors in 62 children with ALL and 120 children with JIA from 31 international centres. Data analysis was performed using two sided Pearson 2 or Fisher's exact tests. Results-Table 5 shows the results obtained. Using multivariate analysis and regression modelling, we evaluated further several predictive models for ALL. The best were: (a) two of three factors present (1/3 haematological values low, raised lactate dehydrogenase (LDH), night time pain; sensitivity 76%, specificity 86%); (b) blasts + 2 of 3 criteria (1/3 haematological values low, raised LDH, night time pain; sensitivity 81%, specificity 86%). These two models, as well as night time pain and raised LDH, and abnormal x rays by themselves, may be useful in diVerentiating a child with leukaemia from a child with JIA and indicating the need for a bone marrow examination. 7.26 ANA detection by recombinant antigens in juvenile idiopathic arthritis and connectivitis

Mediterranean Journal of Rheumatology, 2020

Background: The programmed cell death protein-1 (PD-1) and its ligands (PD-L 1 and 2) suppress im... more Background: The programmed cell death protein-1 (PD-1) and its ligands (PD-L 1 and 2) suppress immune responses, thus promoting self-tolerance. Among the immunomodulatory cells, acting through the PD-1 pathway, are the B-regulatory cells (Bregs). The role of the PD-1 pathway in Juvenile Idiopathic Arthritis (JIA) has not been adequately studied. Aims of the study: To investigate the immunophenotypic profile of T-and B-cells and the activity of the PD-1 pathway in JIA patients. More specifically, we will examine the levels of: a) the soluble form of PD-1 (sPD-1), b) Bregs; and the expression levels of: c) PD-1 on CD4+ and CD8+ T-cells, d) PD-L1 on Bregs and CD19+ B-cells, in blood and synovial fluid samples, at various stages of the disease (onset, relapse, remission, on or off treatment). The above biomarkers will be investigated for correlation with JIA activity. Methods: A case-control study of JIA patients (expected number: 60) and healthy controls (n: 20). Total expected number of samples: 100 of peripheral blood, 120 of serum (solely for soluble markers) and 60 of synovial fluid. The patients' demographic data and treatment will be recorded. JIA will be classified according to the ILAR and the recently proposed PReS/PRINTO criteria. JIA activity will be assessed using the JADAS-10 tool. The biomarkers will be determined using multiparametric-polychromatic flow cytometry (quintuple fluorescence protocol) and immunoenzymatic assay ELISA. Anticipated benefits: Further elucidation of the immunophenotypic expression and variation of the abovementioned molecules and cells during active inflammation and remission in JIA. Thereby, the present

Rheumatology International, 2018

To assess longitudinally the course and outcome of juvenile idiopathic arthritis (JIA) in patient... more To assess longitudinally the course and outcome of juvenile idiopathic arthritis (JIA) in patients diagnosed and followed-up exclusively in the biologic era; also, to define possible predictors of the disease progression and need for early implementation of biologicals. Prospective and retrospective, monocentric cohort study of 120 JIA patients, diagnosed between 2001 and 2010, and followed-up for ≥ 4 years (median 8.04). Disease activity, cumulative articular/extra-articular damage and quality of life were evaluated by the assessment tools Juvenile Arthritis Disease Activity Score (JADAS71), Juvenile Arthritis Damage Index (JADI) and Childhood Health Assessment Questionnaire (CHAQ), respectively. Moreover, potential predictors of the disease progression and their relation to biologic therapy were investigated. High JADAS71 score (> 9) at diagnosis was indicative of progression to polyarticular course and the need for early introduction of biologic treatment. Other independent predictors of progression to polyarthritis, were: involvement of upper limb, hip and ankle within 6 months following JIA diagnosis and percentage of cumulative time with active disease > 35% within the first year. At the end of the study, both the median JADAS71 score and the Disability Index were significantly lower than the initial (p < 0.001) and remission off medication was achieved in 25% of the patients. Articular and extra-articular (only ocular) cumulative damage was demonstrated only in 5 and 7.5% of patients, respectively. Physical functional ability was found normal/mildly restricted in 93.3% and moderately restricted in 6.7% of the patients. We believe that these findings, fit in with a picture of JIA course and outcome under current conditions of objective "disease status" evaluation and of tightly controlled follow-up. Predictors emerged from our study could contribute to the identification of patients who will need early implementation of biologic treatment.

Paediatric rheumatology, 2018

Background: Therapy of oligoarticular JIA is based on intrarticular injections of steroids, metho... more Background: Therapy of oligoarticular JIA is based on intrarticular injections of steroids, methotrexate and biotechnological therapy. ANAs-positive oligoarticular JIA patients with an early onset of disease have a consistent risk to develop uveites. Objectives: The primary aim of this study is to evaluate longitudinally the effect of non-systemic therapy and of systemic immmunomodulating drugs (e.g MTX) on ANAs in JIA patients; secondary occurance of iridocyclitis was evaluated. Methods: Monocentric retrospective not randomised study of 40 patients affected by oligoarticular JIA (ILAR classification) with ANA positivity at the baseline (T0, time of diagnosis). Patient of Group 1 received only intra-articular infiltrations or NSAID. Patients of Group 2 were treated with DMARDs (most of them with subcutaneous MTX 15 mg/m2/week) or MTX +biotechnlogical therapies. The assay for ANAs (I.I.F.) was assessed in all patients at T0, at T1 (12 months) and T2 (24 months). At 24 months was also recorded the occurence of uveitis during the follow up. Exclusion criteria were the ANAs negativity at T0 and other subgroups of JIA. Results: Twenty-one patients (52,5%) were treated with non-systemic therapy (Group 1), and ninenteen (47,5%) with systemic immunomodulating therapy (Group 2). In Group 2 fifteen subjects were treated with MTX, one with MTX plus cyclosporine, one with only cyclosporine, two with MTX plus biotechnological agent (etarnecept and adalimumab). At T1, in Group 1 only one patient out of 20 (4,8%) became ANAs negative versus 42,1% (8/19) of patients in Group 2 (p 0.0033). At T2 the incidence of ANAs positivity did not change in Group 1 (only 1/ 21 ANAs negative), while 42,1% of patients treated with systemic therapies were ANA negative (p 0.006). Three patients were lost at the follow up. The two patients who received bDMARDs in addition to MTX remained ANAs-positive both in T1 and T2. At the end of follow-up period eight uveitis have occured, six in ANAs positive patients of Group 1 (6/21, 28,5%) and two in ANA negatives patients in Group 2 (2/19, 10,5%). Conclusions: ANAs-positive patients treated with methotrexate seems to have higher possibility to became ANAs-negative versus patients treated with non-systemic immunomodulating therapy. It's known that MTX might prevent onset of uveitis in JIA, as shown in our results. Demostrating a negativization of antinuclear antibodies using MTX therapy could help to add a role of this drug in the disease history of the oligoarthritis.

World journal of pediatrics : WJP, Jan 22, 2017

To evaluate the performance of the Quantiferon(®)-TB Gold In-Tube (QFT-IT) interferon (IFN)-γ ass... more To evaluate the performance of the Quantiferon(®)-TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Agreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay...

Clinical and Experimental Immunology, 2017

Summary The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will faci... more Summary The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non-invasive diagnosis, follow-up and more appropriate use of treatment. The aim of this study was to explore the role of serum high-mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti-NCS), complement factor C1q (anti-C1q) and glomerular basement membrane (anti-GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme-linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti-NCS, anti-GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without rena...

Journal of Clinical Immunology

Pediatric Rheumatology, 2014

Kanakoudi-Tsakalidou et al.: B lymphocyte stimulator, interferon-α and HMGB 1 interrelation in ch... more Kanakoudi-Tsakalidou et al.: B lymphocyte stimulator, interferon-α and HMGB 1 interrelation in childhood onset systemic lupus erythematosus: associations with disease activity and severity.

Clinical and experimental rheumatology

Assessment of the post-etanercept (ET) disease course in patients with juvenile idiopathic arthri... more Assessment of the post-etanercept (ET) disease course in patients with juvenile idiopathic arthritis (JIA) who discontinued the drug due to disease remission, using a recently developed tool that scores the disease activity. Eleven patients (F/M 9/2, median age 9.2 years), with either a polyarthritis' (9) or an oligoarthritis' (2) disease course were followed up for 12.25-27 months after ET withdrawal. The median treatment period under ET was 36 months. The Juvenile Arthritis Disease Activity Score (JADAS) was used to grade the JIA activity at the time of ET commencement, at discontinuation and at the time of the flare. All 11 patients flared during the follow-up period. Compared to the time of ET initiation, JADAS was significantly reduced at ET discontinuation as well as at the time of the flare (26.3 to 0 and to 9.5 respectively, p<0.001). The median remission following ET discontinuation lasted 3 months. The flares were controlled with methotrexate±cyclosporine A in 1...

Clinical and experimental rheumatology

To study the immunogenicity, safety and efficacy of influenza vaccine in children with chronic rh... more To study the immunogenicity, safety and efficacy of influenza vaccine in children with chronic rheumatic diseases (CRD) receiving long-term immunosuppressive therapy. Seventy children (F:M 51:19) with CRD (JIA = 49, SLE = 11, other = 10) aged 4-17 yrs and 5 healthy siblings of the patients (aged < 11 yrs) received a "split type" influenza vaccine (Fluarix SB) licensed for the 1999-2000 winter season. Clinical and laboratory evaluation were performed at study entry and at 1, 3 and 6 months after vaccination. Blood samples were collected before and one month after vaccination and antibody titers to A/Beijing, A/Sydney and B/Beijing influenza antigens were measured using a standardized hemagglutination inhibition assay. Patients were assigned to groups according to the therapeutic regimen [prednisone (PDN), PDN plus 1 disease modifying antirheumatic drug (DMARD), PDN plus 2 DMARDs and 1 or 2 DMARDs without PDN]. 5/70 patients reported local (3) or systemic (2) reactions an...

Vaccine, 2010

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valen... more Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 ± 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p < 0.0001) in both groups and were found to be protective (>0.35 g/ml) in 87-100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p < 0.05). A ≥4-fold increase of the baseline titers to ≥5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares.

Scandinavian Journal of Rheumatology, 2010

To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile i... more To evaluate the safety and efficacy of adalimumab (AD) administration in patients with juvenile idiopathic arthritis (JIA). Twenty-six patients were enrolled from January 2004 to January 2008 in this prospective observational study. Inclusion criteria were either unresponsiveness to disease-modifying anti-rheumatic drugs (DMARDs; n = 17) or to other anti-tumour necrosis factor (anti-TNF) agents (n = 9) or development of uveitis under other anti-TNFs (n = 2 of the 9). Efficacy was estimated using the American College of Rheumatology Pediatric (ACR Pedi) criteria. After 1-5 years of AD exposure, nine different adverse events (AEs) were recorded (12.6 AEs/100 patient-years), mainly mild respiratory tract infections and injection site-related reactions. Serious AEs (SAEs, 2.8/100 patient-years) were the development of abscess at the site of injection (n = 1) and lethal sepsis (n = 1). The ACR Pedi ≥ 30 responses for the first to the fifth year of treatment were 88.5, 57.7, 50.0, 34.6, and 11.5%, respectively. In total, 17 of the 26 (65.4%) patients responded to AD. Five of the 11 patients under steroids discontinued them 6 months post-treatment. Seven patients required weekly AD treatment to maintain remission and four of them benefited from this policy. Recurrent uveitis was hindered in three of the six patients, no new cases were recorded, and radiological regression was observed in two of the four patients with lesions. AD was safe and efficacious during the study period in the majority of patients. However, vigilance is required for the early detection of severe and potentially fatal infections. AD may control recurrent uveitis and radiological progression.

Pediatric Rheumatology, 2008

To evaluate the 5-yr use of 2 anti-TNF preparations, Etanercept (ET) and Adalimumab (AD), in chil... more To evaluate the 5-yr use of 2 anti-TNF preparations, Etanercept (ET) and Adalimumab (AD), in children with refractory to conventional treament JIA.

Pediatric Rheumatology, 2011

Pediatric Rheumatology, 2011

Pediatric Rheumatology, 2008

Recent data in adult Rheumatoid Arthritis support that the Th17 cell-derived cytokine interleukin... more Recent data in adult Rheumatoid Arthritis support that the Th17 cell-derived cytokine interleukin 17 (IL-17) in the presence of IL-6 and IL-23 plays a critical role in the pathogenesis of chronic destructive arthritis. Data on synovial fluid (SF) concentrations of IL-17 in JIA pts are sparse. We measured concentrations of the above 3 cytokines and assessed the CD4+CD25 high FoxP3+ (Treg) and CD4+CD25 low FoxP3-T cell subpopulations in the SF of children with JIA. Findings were correlated with SF sRANKL which expresses the osteoclastic activity in active disease.

Pediatric Blood & Cancer, 2008

To the Editor: Osteonecrosis (ON) of the femoral head has been described in patients with sickle ... more To the Editor: Osteonecrosis (ON) of the femoral head has been described in patients with sickle cell disease [1], malignancies [2] and juvenile idiopathic arthritis (JIA) receiving prednisone (PDN) [3]. We present a 15-year-oldale with a systemic JIA onset, who developed secondary ON mimicking ‘‘skip’’ lesions of bone malignancy due to its unusual location in the lower part of her right thigh. Fourteen months following diagnosis, while in disease remission, she complained of a persistent femur pain. It was a continuous dull pain, with no history of trauma, aggravated by the routine physical activities, resolving with rest and responding to analgesics. Her previous regimen included methotrexate (MTX) 15 mg/m/week, cysclosporine (CSA) 3 mg/kg/day and PDN 2 mg/ kg for the first 2 months, following tapering that ended to 0.25 mg/ kg/day for the last 5 months. X-rays and MRI revealed lesions in the right femoral diaphysis and distal metaphysis suspicious of an osteosarcoma (Fig. 1). The double phase scan TI-201 did not show any radiotracer uptake and was felt to exclude malignancy. To make a definitive diagnosis, an open biopsy was performed. The specimen consisted of pieces of lamellar bone, woven bone, striated muscle and necrotic material. It was compatible either with a healing bone fracture and/or ON. She was conservatively managed by gradual withdrawal of PDN, restriction of weight bearing; she returned to her regular activities 2 months later. After a 5-year follow-up, her radiographs and MRI showed healing sclerotic lesions of the ON area with no bone marrow oedema or periosteal reaction or any soft tissue mass. ON of the femoral bone in patients with pediatric rheumatic diseases receiving long-term PDN is unusual [4,5]. We assume that PDN was the exclusive contributor to the development of ON, as data on the association of MTX or CSA with ON have not been reported. The femoral head is the most common and clinically significant site of ON, while the femoral shaft of JIA patients has not previously been reported. In adults using steroids or following radiation, insufficient fractures of the sacrum have been misdiagnosed as malignancies [6]. On the other hand, Fujimoto et al. [7] emphasized that a metastatic femur tumor can mimic spontaneous ON and have a misleading appearance on MRI imaging. We were faced with the same dilemma due to the unusual location of the ON lesions and the misleading imaging that was consistent with that of a bone tumor. Thallium scintigraphy was an important piece of data as it appeared inconsistent with malignancy [8]. However, a biopsy might be necessary to support such a diagnosis of ON, as occurred in our patient. This case highlights the importance of including ON in the differential diagnosis for bone pain of any patient receiving steroids.

Mycoses, 2001

We report the ®rst case of hepatitis due to Aspergillus terreus in a 13-year-old boy with common ... more We report the ®rst case of hepatitis due to Aspergillus terreus in a 13-year-old boy with common variable immunode®ciency that occurred while the patient was receiving secondary prophylaxis with¯uconazole after an episode of pulmonary candidosis. The infection subsided after the addition of itraconazole to the combination of liposomal amphotericin B and granulocyte-macrophage colony-stimulating factor that he was receiving. Zusammenfassung. Es wird zum ersten Mal u È ber eine Hepatitis berichtet, bedingt durch Aspergillus terreus, bei einem 13-ja Èhrigen Jungen mit Immunde®zienz wa Èhrend der sekunda Èren Fluconazol-Prophylaxe nach Lungen-Candidose. Die Aspergillose ging zuru È ck nach Applikation von liposomalem Amphotericin B, kombiniert mit Itraconazol und Granulozyten-Makrophagen-Kolonie-stimulierendem Faktor.