Ljudmila Stojanovich | University of Belgrade (original) (raw)
Papers by Ljudmila Stojanovich
Objectives: To present the systematic literature review (SLR), which formed the basis for the Eur... more Objectives: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). Methods: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. Results: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. Conclusion: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.
Objective: To describe the characteristics of patients with peripheral vascular disease leading t... more Objective: To describe the characteristics of patients with peripheral vascular disease leading to amputation of digits or limbs encountered in patients with the antiphospholipid syndrome (APS). Methods: Twenty-one cases derived from several geographical centers (Brazil, Serbia, Italy, Israel, United Kingdom, and South Africa) are presented. The major clinical, serological, and histopatho-logical data (where available) of this cohort are described, documented, and analyzed. Results: Patients were suffering mainly from systemic lupus erythematosus (9 patients) or primary APS (8 patients). Peripheral vascular occlusions occurred during the course of the catastrophic APS in 5 patients. The vascular occlusions occurred both early and very late in the course of the disease (time after APS diagnosis, 0-38 years). Vasculitis was present in 7 patients and 5 demonstrated the typical antiphospho-lipid antibody (aPL)—vasculopathy with complicating bland thrombosis. Myocardial infarctions had occurred in 4 patients but it was not possible to determine whether they suffered from premature atherosclerotic disease or whether the infarctions were aPL-related. The appearance of livedo reticularis preceding the arterial thrombosis was noted in 9 patients. Cryoglobulinemia was detected in only 1 patient. Conclusions: Peripheral vascular disease leading to amputation of digits or limbs is a severe complication encountered in patients with APS. In the absence of histopathology, it may be difficult to distinguish whether concomitant atherosclerotic occlusions, vasculitis, or aPL-related thrombosis of peripheral vessels is the main cause of the vascular ischemia. Treatment should, therefore, include full anticoagulation as well as corticosteroids and immunosuppression in these patients.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright The etiology of autoimmune disease is multifactorial, including genetic, environmental, hormonal, and immunological factors. Nevertheless, the onset of autoimmune disorders remains enigmatic. Physical and psychological stresses have been suggested in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of stressors on immune function. Moreover, many retrospective studies had found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. This, however, is not surprising as the disease itself causes significant stress in the patient. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease and presume that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease by altering or amplifying cytokine production. However, there is no evidence based research to support this concept. Nonetheless, stress reactions should be discussed with autoimmune patients. Applied implications are discussed, concentrating on the need for multidisciplinary care interventions that target patients' disease symptoms and help them cope with their illness.
Your article is protected by copyright and all rights are held exclusively by International Leagu... more Your article is protected by copyright and all rights are held exclusively by International League of Associations for Rheumatology (ILAR). This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Clinical and Experimental Rheumatology, 2014
A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of pat... more A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of patients with systemic lupus erythematosus (SLE) and correlates with the presence of autoantibodies. Antiphospholipid syndrome (APS) can develop secondary to SLE or as a primary disease. In the current study we investigated the ability of sera from patients with APS to degrade NETs. The presence of antibodies against NETs and neutrophil remnants were also determined in the same patients.
American Journal of Clinical and Experimental Immunology, 2012
Autoimmun Rev, 2011
To present the systematic literature review (SLR), which formed the basis for the European League... more To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD).AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible.Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive.Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.
The Israel Medical Association Journal Imaj, Aug 1, 2007
Annals of the Rheumatic Diseases, 2015
Clinical and experimental rheumatology
Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients wit... more Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome).
Bilten za hematologiju i transfuziju
Vojnosanitetski pregled. Military-medical and pharmaceutical review
The aim of this study was to evaluate the role of antiphospholipid antibodies (APA) in human repr... more The aim of this study was to evaluate the role of antiphospholipid antibodies (APA) in human reproduction. The investigation included 150 patients with systemic lupus erythematosus (SLE), and a group of 931 women, with the history of recurrent spontaneously miscarried pregnancies of unknown origin, even after a detailed examination in obstetric-gynecological institution. APA were investigated by means of tests to lupus anticoagulant (LA), applying a set of coagulation tests, including two tests with viper's poison, and cardiolipin antibodies (ACL) were determined by a standard immunoenzyme method, where a cardiolipin (Sigma, USA) was used as an antigen. The analysis of obstetric history in women with SLE has shown a considerable increase in frequency of obstetric complications in APA-positive group of patients (p < 0.001). Screening-examination to APA, proved its presence in 254 of the total of 931 women (27%), and a complete evaluation of the positive group enabled the estab...
Arthritis Research & Therapy
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with define... more We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.
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The Journal of rheumatology, Jan 15, 2015
Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome... more Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome, but can also be detected in patients with rheumatoid arthritis and in patients positive for lupus anticoagulants and thus potentially antiphospholipid syndrome (APS). To our knowledge, no data are available on the association between the presence of FH autoantibodies in APS and clinical manifestations. We determined FH autoantibody levels using ELISA in 2 cohorts of patients with primary (PAPS) and secondary APS (SAPS) from Serbia and Italy, and an additional cohort including patients with venous thromboembolism (VTE) from Sweden. FH autoantibodies were detected in 13.7% of patients (n = 73) with PAPS and 30.3% of patients (n = 33) with SAPS in the Serbian cohort. FH autoantibody frequency in the Italian cohort was 33.3% (n = 15) and 36% (n = 25) in PAPS and SAPS, respectively. Both FH autoantibody levels and frequencies observed in both APS cohorts were significantly higher than in ma...
Immunobiology, 2013
The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-ind... more The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-inducing cytokines IL-23 and transforming growth factor (TGF)-β, as well as IL-17 single nucleotide polymorphism (SNP) rs2275913 in patients with primary antiphospholipid syndrome (PAPS). We studied fifty patients with PAPS and fifty age- and sex-matched healthy controls. The cytokine levels were measured by ELISA, while the rs2275913 SNP located in promoter region of IL-17 gene was genotyped using real-time PCR. The significantly higher levels of IL-17 (p=0.002), IL-23 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and TGF-β (p=0.042) were found in PAPS patients (median 13.1, 9.4, and 125.6 pg/ml, respectively) compared to the control group (6.8, 4.9 and 44.4 pg/ml). There was a significant positive correlation between concentrations of IL-17 and IL-23 (r=0.540, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), but not between those of IL-17 and TGF-β. No statistically significant differences were observed in the distribution of genotypes and alleles of the IL-17 rs2275913 variants in patients with PAPS compared to healthy subjects. The blood concentrations of IL-17 did not differ in subjects with different rs2275913 genotypes or patients with or without antiphospholipid antibodies. Finally, a trend toward higher IL-17 levels (p=0.063) and the significantly higher IL-17 concentrations (p=0.012) were observed in PAPS patients with deep vein thrombosis and thrombocytopenia, respectively. These data demonstrate that IL-23/IL-17 axis, stimulated independently of TGF-β increase IL-17A gene polymorphism and antiphospholipid antibody production, might contribute to vascular manifestations of PAPS.
Annals of the Rheumatic Diseases, 2014
ABSTRACT Objectives Antiphospholipid syndrome (APS) patients suffer from various clinical manifes... more ABSTRACT Objectives Antiphospholipid syndrome (APS) patients suffer from various clinical manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease (SAPS), most commonly in the context of Systemic Lupus Erythemathosus (SLE) Methods We analyzed 488 patients: 346 PAPS (70.9%) (77.7% female and 22.3% male) average age 44.1±13.0 years and 142 patients with secondary APS (SLE) patients (29.1%) (90.8% female and 9.2% male) average age 47.2±14.8 years. aPL analysis included analysis of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. aPL analysis included analysis of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. In all patients data considering cardiac, vascular, pulmonary, neurological, skin and hematological disorders were collected. Results There was 30.8% aCL-IgG, 49.7% aCL-IgM, 31.4% β2GPI IgG, 40.4% β2GPI IgM and 54.0% LA positive PAPS patients. Among SAPS patients 57.9% were aCL-IgG, 61.4% aCL-IgM, 40.7% β2GPI IgG, 45.0% β2GPI IgM and 51.1% LA positive. We observed 56.3% with neurological, 23.0% patients with skin, 27.3% with cardiac, 20.8% with hematological and 15.2% with pulmonary disorders. 54.3% of patients had peripheral vascular thrombosis (arterial, venous or both) in PAPS and 70.4% SAPS patients with skin, 77.3% with neurological, 40.8% with cardiac, 64.8% with hematological and 12.0% with pulmonary disorders. 57.9% of SAPS patients had peripheral vascular thrombosis. Between SAPS and PAPS patients we observed highly statisticaly significant difference considering neurological (p=0.0001), cardiac (p=0.002), skin (p=0.0001) and hematological manifestations (p=0.0001) in favour of patients with SAPS. Conclusions Patients with SAPS suffer more often from various clinical features comparing to patients PAPS. Additional autoimmune burden in those patients presented through aPL presence besides actual autoimmune disease pannel, could be an explanation. References Acknowledgements This work was supported by research grant number 175041 for 2011-2014, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2428
Annals of the Rheumatic Diseases, 2013
ABSTRACT Background Patients with antiphospholipid syndrome (APS) have an increased risk of ather... more ABSTRACT Background Patients with antiphospholipid syndrome (APS) have an increased risk of atherosclerosis. Objectives The aim of our study was to determine whether there are subclinical arterial changes in APS patients, and what is the best diagnostic choice for their establishment. Methods In this study we analyzed 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with Systemic Lupus Erythematosus and APS (SAPS). The results were compared to 30 controls. The groups were comparable with respect to age, gender, and traditional risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. Study was conducted on 64-multi-sliced computed tomography (64-MSCT) and only the new changes that have not been verified until this exam were taken into analysis. Results There was significantly higher incidence of overall arterial changes in PAPS and SAPS patients, as compared to healthy controls. We detected a total of 70 arterials stenosis in PAPS patients, and 79 arterial stenosis in SAPS patients, compared to 43 in the control group (χ2=16.95, p <0,001, χ2=30.14, p <0,001, respectively). There were 20 newly discovered visceral blood vessel lesions in the patients with APS and 5 lesions in the control group. There was significantly higher incidence of overall visceral arterial changes comparing to controls since in PAPS patients the sum of 10 and in SAPS the sum of 5 arterials stenosis compared to 5 in control group was detected (p< 0.001). Significant changes in PAPS and SAPS patients comparing to controls were detected on celiac artery (10pts vs.3pts vs. 3pts; p< 0.05), superior mesenteric artery (6pts vs. 2pts. vs. 0pts; p< 0.05) and right renal artery (4pts vs. 0 pts. vs. 2pts; p< 0.05). Conclusions APS patients suffer from accelerated atherosclerosis, and the 64-MSCT angiography is the method of choice in monitoring disease progression, because it is a safe, has the lowest degree of error, and provides an overview of the arteries that are otherwise difficult to access. This enables timely treatment of these patients with drugs or interventional radiology procedures References References Acknowledgements We thank all patients who participated in this study and our colleagues from many clinics in Serbia. This work was supported by research grant number 175041 for 2011 - 2014, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None Declared
Atherosclerosis Supplements, 2011
in women and 10.2 in men (P = 0.003). We found a direct correlation between AIx and cIMT (r = 0.3... more in women and 10.2 in men (P = 0.003). We found a direct correlation between AIx and cIMT (r = 0.32, P < 0.0001). Those patients with hypertension (n = 364), dyslipidaemia (n = 543) or metabolic syndrome (n = 543) presented a positive correlation between AIx and cIMT (r = 0.17 and P = 0.004, r = 0.21 and P = 0.001, r = 0.27 and P < 0.0001, respectively) while this was not observed in the type 2 DM group (n = 224). In the multivariate analysis, AIx was one of the main predictors of cIMT (B = 0.016, P < 0.001) along with male gender, age, LDLc levels, and systolic blood pressure. In patients with hypertension or metabolic syndrome we found that age, male gender, hsCRP were the determinants, while in the dyslipidaemia group were age, male gender, AIx and LDLc levels.
Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952), 1990
The clinical manifestations of Sneddon's syndrome (cerebrovascular disorder, livedo reticular... more The clinical manifestations of Sneddon's syndrome (cerebrovascular disorder, livedo reticularis, peripheral venous thrombosis++, cardiac pathology, obstetric pathology--fetal loss and intrauterine fetal death) are characteristic of the antiphospholipid syndrome. A lupus anticoagulant (LA), one of the types of antiphospholipid antibodies, was detected in the blood plasma of 18 out of 30 patients with Sneddon's syndrome. The negative results of LA-examination in 12 patients don't exclude the presence of other antiphospholipid antibodies. So 16 of 30 patients had anticardiolipin antibodies, among them being 6 LA-negative patients. The authors discuss the significance of antiphospholipid antibodies in the genesis of vascular abnormalities in patients with Sneddon's syndrome.
Objectives: To present the systematic literature review (SLR), which formed the basis for the Eur... more Objectives: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). Methods: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. Results: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. Conclusion: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.
Objective: To describe the characteristics of patients with peripheral vascular disease leading t... more Objective: To describe the characteristics of patients with peripheral vascular disease leading to amputation of digits or limbs encountered in patients with the antiphospholipid syndrome (APS). Methods: Twenty-one cases derived from several geographical centers (Brazil, Serbia, Italy, Israel, United Kingdom, and South Africa) are presented. The major clinical, serological, and histopatho-logical data (where available) of this cohort are described, documented, and analyzed. Results: Patients were suffering mainly from systemic lupus erythematosus (9 patients) or primary APS (8 patients). Peripheral vascular occlusions occurred during the course of the catastrophic APS in 5 patients. The vascular occlusions occurred both early and very late in the course of the disease (time after APS diagnosis, 0-38 years). Vasculitis was present in 7 patients and 5 demonstrated the typical antiphospho-lipid antibody (aPL)—vasculopathy with complicating bland thrombosis. Myocardial infarctions had occurred in 4 patients but it was not possible to determine whether they suffered from premature atherosclerotic disease or whether the infarctions were aPL-related. The appearance of livedo reticularis preceding the arterial thrombosis was noted in 9 patients. Cryoglobulinemia was detected in only 1 patient. Conclusions: Peripheral vascular disease leading to amputation of digits or limbs is a severe complication encountered in patients with APS. In the absence of histopathology, it may be difficult to distinguish whether concomitant atherosclerotic occlusions, vasculitis, or aPL-related thrombosis of peripheral vessels is the main cause of the vascular ischemia. Treatment should, therefore, include full anticoagulation as well as corticosteroids and immunosuppression in these patients.
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright The etiology of autoimmune disease is multifactorial, including genetic, environmental, hormonal, and immunological factors. Nevertheless, the onset of autoimmune disorders remains enigmatic. Physical and psychological stresses have been suggested in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of stressors on immune function. Moreover, many retrospective studies had found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. This, however, is not surprising as the disease itself causes significant stress in the patient. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease and presume that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease by altering or amplifying cytokine production. However, there is no evidence based research to support this concept. Nonetheless, stress reactions should be discussed with autoimmune patients. Applied implications are discussed, concentrating on the need for multidisciplinary care interventions that target patients' disease symptoms and help them cope with their illness.
Your article is protected by copyright and all rights are held exclusively by International Leagu... more Your article is protected by copyright and all rights are held exclusively by International League of Associations for Rheumatology (ILAR). This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Clinical and Experimental Rheumatology, 2014
A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of pat... more A decreased ability to degrade neutrophil extracellular traps (NETs) is seen in a subgroup of patients with systemic lupus erythematosus (SLE) and correlates with the presence of autoantibodies. Antiphospholipid syndrome (APS) can develop secondary to SLE or as a primary disease. In the current study we investigated the ability of sera from patients with APS to degrade NETs. The presence of antibodies against NETs and neutrophil remnants were also determined in the same patients.
American Journal of Clinical and Experimental Immunology, 2012
Autoimmun Rev, 2011
To present the systematic literature review (SLR), which formed the basis for the European League... more To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD).AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible.Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive.Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.
The Israel Medical Association Journal Imaj, Aug 1, 2007
Annals of the Rheumatic Diseases, 2015
Clinical and experimental rheumatology
Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients wit... more Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome).
Bilten za hematologiju i transfuziju
Vojnosanitetski pregled. Military-medical and pharmaceutical review
The aim of this study was to evaluate the role of antiphospholipid antibodies (APA) in human repr... more The aim of this study was to evaluate the role of antiphospholipid antibodies (APA) in human reproduction. The investigation included 150 patients with systemic lupus erythematosus (SLE), and a group of 931 women, with the history of recurrent spontaneously miscarried pregnancies of unknown origin, even after a detailed examination in obstetric-gynecological institution. APA were investigated by means of tests to lupus anticoagulant (LA), applying a set of coagulation tests, including two tests with viper's poison, and cardiolipin antibodies (ACL) were determined by a standard immunoenzyme method, where a cardiolipin (Sigma, USA) was used as an antigen. The analysis of obstetric history in women with SLE has shown a considerable increase in frequency of obstetric complications in APA-positive group of patients (p < 0.001). Screening-examination to APA, proved its presence in 254 of the total of 931 women (27%), and a complete evaluation of the positive group enabled the estab...
Arthritis Research & Therapy
We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with define... more We discuss the presence of anti-keratin antibodies (AKA) of the IgG class in patients with defined juvenile idiopathic arthritis (JIA). An indirect immunofluorescence test and rat oesophagus substrate was used for the detection and quantification of AKA antibodies in patients´ sera. Overall 33/60 patients with JIA had sera positive for AKA (55 %, P = 0,0001) ranging from 1:10 to 1:160 dilutions. Following idiopathic arthritis of childhood classification criteria AKA occurred in 2/7 patients with systemic disease (28,6 %), in 13/30 patients with RF negative polyarthritis (43,3 %, P = 0,008) and in 15/18 RF positive polyarthritis (83,3 %, P = 0,000002). AKA were also found in a small cohort of patients with oligoarthritis (1/3) and psoriatic arthritis (2/2). AKA positivity occurred in 3/26 healthy controls at a 1:20 dilution. The presence of AKA was correlated as well as with the severity of the disease. Our study revealed that AKA was present overall in 18/29 patients (62%) with severe JIA and in 12/26 patients (46,2 %) with non-severe disease, however this did not reach statistical significance (P = 0,18). We also observed that AKA remained positive regardless of disease activity. AKA were detectable in 55,6 % patients with active JIA and in 48,6 % patients in the complete or near remission.
The Journal of rheumatology, Jan 15, 2015
Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome... more Autoantibodies to complement factor H (FH) are associated with atypical hemolytic uremic syndrome, but can also be detected in patients with rheumatoid arthritis and in patients positive for lupus anticoagulants and thus potentially antiphospholipid syndrome (APS). To our knowledge, no data are available on the association between the presence of FH autoantibodies in APS and clinical manifestations. We determined FH autoantibody levels using ELISA in 2 cohorts of patients with primary (PAPS) and secondary APS (SAPS) from Serbia and Italy, and an additional cohort including patients with venous thromboembolism (VTE) from Sweden. FH autoantibodies were detected in 13.7% of patients (n = 73) with PAPS and 30.3% of patients (n = 33) with SAPS in the Serbian cohort. FH autoantibody frequency in the Italian cohort was 33.3% (n = 15) and 36% (n = 25) in PAPS and SAPS, respectively. Both FH autoantibody levels and frequencies observed in both APS cohorts were significantly higher than in ma...
Immunobiology, 2013
The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-ind... more The aim of the study was to investigate serum concentrations of interleukin (IL)-17 and IL-17-inducing cytokines IL-23 and transforming growth factor (TGF)-β, as well as IL-17 single nucleotide polymorphism (SNP) rs2275913 in patients with primary antiphospholipid syndrome (PAPS). We studied fifty patients with PAPS and fifty age- and sex-matched healthy controls. The cytokine levels were measured by ELISA, while the rs2275913 SNP located in promoter region of IL-17 gene was genotyped using real-time PCR. The significantly higher levels of IL-17 (p=0.002), IL-23 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and TGF-β (p=0.042) were found in PAPS patients (median 13.1, 9.4, and 125.6 pg/ml, respectively) compared to the control group (6.8, 4.9 and 44.4 pg/ml). There was a significant positive correlation between concentrations of IL-17 and IL-23 (r=0.540, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), but not between those of IL-17 and TGF-β. No statistically significant differences were observed in the distribution of genotypes and alleles of the IL-17 rs2275913 variants in patients with PAPS compared to healthy subjects. The blood concentrations of IL-17 did not differ in subjects with different rs2275913 genotypes or patients with or without antiphospholipid antibodies. Finally, a trend toward higher IL-17 levels (p=0.063) and the significantly higher IL-17 concentrations (p=0.012) were observed in PAPS patients with deep vein thrombosis and thrombocytopenia, respectively. These data demonstrate that IL-23/IL-17 axis, stimulated independently of TGF-β increase IL-17A gene polymorphism and antiphospholipid antibody production, might contribute to vascular manifestations of PAPS.
Annals of the Rheumatic Diseases, 2014
ABSTRACT Objectives Antiphospholipid syndrome (APS) patients suffer from various clinical manifes... more ABSTRACT Objectives Antiphospholipid syndrome (APS) patients suffer from various clinical manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease (SAPS), most commonly in the context of Systemic Lupus Erythemathosus (SLE) Methods We analyzed 488 patients: 346 PAPS (70.9%) (77.7% female and 22.3% male) average age 44.1±13.0 years and 142 patients with secondary APS (SLE) patients (29.1%) (90.8% female and 9.2% male) average age 47.2±14.8 years. aPL analysis included analysis of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. aPL analysis included analysis of aCL (IgG/IgM), β2GPI (IgG/IgM) and LA. In all patients data considering cardiac, vascular, pulmonary, neurological, skin and hematological disorders were collected. Results There was 30.8% aCL-IgG, 49.7% aCL-IgM, 31.4% β2GPI IgG, 40.4% β2GPI IgM and 54.0% LA positive PAPS patients. Among SAPS patients 57.9% were aCL-IgG, 61.4% aCL-IgM, 40.7% β2GPI IgG, 45.0% β2GPI IgM and 51.1% LA positive. We observed 56.3% with neurological, 23.0% patients with skin, 27.3% with cardiac, 20.8% with hematological and 15.2% with pulmonary disorders. 54.3% of patients had peripheral vascular thrombosis (arterial, venous or both) in PAPS and 70.4% SAPS patients with skin, 77.3% with neurological, 40.8% with cardiac, 64.8% with hematological and 12.0% with pulmonary disorders. 57.9% of SAPS patients had peripheral vascular thrombosis. Between SAPS and PAPS patients we observed highly statisticaly significant difference considering neurological (p=0.0001), cardiac (p=0.002), skin (p=0.0001) and hematological manifestations (p=0.0001) in favour of patients with SAPS. Conclusions Patients with SAPS suffer more often from various clinical features comparing to patients PAPS. Additional autoimmune burden in those patients presented through aPL presence besides actual autoimmune disease pannel, could be an explanation. References Acknowledgements This work was supported by research grant number 175041 for 2011-2014, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2428
Annals of the Rheumatic Diseases, 2013
ABSTRACT Background Patients with antiphospholipid syndrome (APS) have an increased risk of ather... more ABSTRACT Background Patients with antiphospholipid syndrome (APS) have an increased risk of atherosclerosis. Objectives The aim of our study was to determine whether there are subclinical arterial changes in APS patients, and what is the best diagnostic choice for their establishment. Methods In this study we analyzed 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with Systemic Lupus Erythematosus and APS (SAPS). The results were compared to 30 controls. The groups were comparable with respect to age, gender, and traditional risk factors except for the lipid status, since controls had significantly higher levels of cholesterol and triglycerides. Study was conducted on 64-multi-sliced computed tomography (64-MSCT) and only the new changes that have not been verified until this exam were taken into analysis. Results There was significantly higher incidence of overall arterial changes in PAPS and SAPS patients, as compared to healthy controls. We detected a total of 70 arterials stenosis in PAPS patients, and 79 arterial stenosis in SAPS patients, compared to 43 in the control group (χ2=16.95, p <0,001, χ2=30.14, p <0,001, respectively). There were 20 newly discovered visceral blood vessel lesions in the patients with APS and 5 lesions in the control group. There was significantly higher incidence of overall visceral arterial changes comparing to controls since in PAPS patients the sum of 10 and in SAPS the sum of 5 arterials stenosis compared to 5 in control group was detected (p< 0.001). Significant changes in PAPS and SAPS patients comparing to controls were detected on celiac artery (10pts vs.3pts vs. 3pts; p< 0.05), superior mesenteric artery (6pts vs. 2pts. vs. 0pts; p< 0.05) and right renal artery (4pts vs. 0 pts. vs. 2pts; p< 0.05). Conclusions APS patients suffer from accelerated atherosclerosis, and the 64-MSCT angiography is the method of choice in monitoring disease progression, because it is a safe, has the lowest degree of error, and provides an overview of the arteries that are otherwise difficult to access. This enables timely treatment of these patients with drugs or interventional radiology procedures References References Acknowledgements We thank all patients who participated in this study and our colleagues from many clinics in Serbia. This work was supported by research grant number 175041 for 2011 - 2014, issued by the Ministry of Science of the Republic of Serbia. Disclosure of Interest None Declared
Atherosclerosis Supplements, 2011
in women and 10.2 in men (P = 0.003). We found a direct correlation between AIx and cIMT (r = 0.3... more in women and 10.2 in men (P = 0.003). We found a direct correlation between AIx and cIMT (r = 0.32, P < 0.0001). Those patients with hypertension (n = 364), dyslipidaemia (n = 543) or metabolic syndrome (n = 543) presented a positive correlation between AIx and cIMT (r = 0.17 and P = 0.004, r = 0.21 and P = 0.001, r = 0.27 and P < 0.0001, respectively) while this was not observed in the type 2 DM group (n = 224). In the multivariate analysis, AIx was one of the main predictors of cIMT (B = 0.016, P < 0.001) along with male gender, age, LDLc levels, and systolic blood pressure. In patients with hypertension or metabolic syndrome we found that age, male gender, hsCRP were the determinants, while in the dyslipidaemia group were age, male gender, AIx and LDLc levels.
Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952), 1990
The clinical manifestations of Sneddon's syndrome (cerebrovascular disorder, livedo reticular... more The clinical manifestations of Sneddon's syndrome (cerebrovascular disorder, livedo reticularis, peripheral venous thrombosis++, cardiac pathology, obstetric pathology--fetal loss and intrauterine fetal death) are characteristic of the antiphospholipid syndrome. A lupus anticoagulant (LA), one of the types of antiphospholipid antibodies, was detected in the blood plasma of 18 out of 30 patients with Sneddon's syndrome. The negative results of LA-examination in 12 patients don't exclude the presence of other antiphospholipid antibodies. So 16 of 30 patients had anticardiolipin antibodies, among them being 6 LA-negative patients. The authors discuss the significance of antiphospholipid antibodies in the genesis of vascular abnormalities in patients with Sneddon's syndrome.