[show abstract][hide abstract] ABSTRACT: Avascular or aseptic necrosis is a well-defined entity leading to the degradation of cellular elements of the bone. The pathogenesis of osteonecrosis (ON) is still unknown. There are two main types of ON: traumatic or non-traumatic. Several clinical entities could associate with ON, systemic diseases, environmental factors, pregnancy, systemic autoimmune or rheumatic diseases, thrombophilia, corticosteroid therapy, cytotoxic dugs, infections, metabolic and hematologic diseases, etc. Corticosteroids (CS) are still the most frequently used therapeutic options in the early phase and during flares of these diseases. Inflammatory cytokines and antibodies have been described to participate in the pathogenesis of ON. The infiltrative disorders of the bone marrow could also contribute to the development of ON. Hereby, we describe a female patient with NHL followed by SLE in whom ON has developed at least in two localisations. Lupus flare, long-term CS therapy, lymphoma relapse or the presence of antiphospholipid antibodies were excluded. Although the bi-localised ON could be contributed to immunologic factors or trauma, the exact aetiology in this case could not be elucidated.
Osteoporosis International 12/2013; · 4.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The stiff-person syndrome is a rare and progressive neuromuscular disease which appears to have an immunpathological basis. It is characterised by painful muscle spasms and stiffness in the proximal muscles, especially those attached to the axial skeleton. The precise pathophysiology is still unknown, but several antibodies have been shown to be present in patients and these antibodies are directed against proteins which play a role in the inhibitor synapse linked to gamma-amino-butyrate. In the first part of the article the authors present two cases. In the second part they present a comprehensive review of our current knowledge about this rare disease. Orv.Hetil., 154(50), 1984-1990.
[show abstract][hide abstract] ABSTRACT: Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline and arginine containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the conventionally used serological assays to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide specific microarray. B-cells were purified from blood by negative selection; antibody producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identifies nearly one third of CCP2-negative, MCV-negative and RF seronegative RA cases. The results with the peptide specific microarray have shown that while most ACPA recognizing the four citrulline peptides are IgG, but some of them specifically recognizing citrulline containing filaggrin peptides (fil311-315 and fil306-326) are IgM, thus may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA producing cells, thus could also be applied to study RA patients' B-cells. This article is protected by copyright. All rights reserved.
[show abstract][hide abstract] ABSTRACT: Behcet's disease is a multisystem autoimmune disease with variable clinial manifestations. The diagnosis may pose a difficult challenge for the clinician, who has to be familiar with the wide spectrum and combination of the symptoms of Behcet's disease. It is considered a rare disease in Hungary, and there are only few reports on Behcet's disease in the Hungarian literature. However, the past history of Hungary, the worldwide growing incidence of the disease, and the authors' experience raise the possibility that the occurrence of the disease is higher than previously thought. In this review the authors present and discuss literature data on the pathogenesis and pathomechanism, as well as their own experience concerning the symptomatology of Behcet's disease in order to promote diagnosis and offer adequate therapy for the patients. The authors presume that the importance of the disease is underestimated in Hungary due to a considerable number of unrecognized cases and they propose to establish a national registry for Behcets disease. Orv. Hetil., 2013, 154, 93-101.
[show abstract][hide abstract] ABSTRACT: Haplotype tagging SNPs of interleukin-23 receptor gene rs1004819, rs7517847, rs7530511, rs2201841, rs1343151 and rs10889677 were determined in 396 patients with rheumatoid arthritis, 190 patients with Crohn's disease, 206 patients with ankylosing spondylitis and 182 controls. Using regression analysis models the rs1004819, rs2201841, and rs10889677 SNPs were found to confer risk for Crohn's disease and ankylosing spondylitis, while rs1343151 had a protective effect in both of these diseases, and the rs2201841 and rs10889677 SNPs showed susceptibility nature for rheumatoid arthritis. Using these SNPs we could study the susceptibility haplotype profiles in these diseases with special attention to the rheumatoid arthritis, first in the literature. Seven different haplotypes could be differentiated. We found that the SNPs exert their susceptibility character in specific haplotype blocks: thus, for rheumatoid arthritis the rs1343151 SNP was risk factor only in a specific haplotype surrounding; this can explain the controversial results published so far about this variant. More importantly, we observed, that while a specific haplotype can confer risk for rheumatoid arthritis, the same haplotype tended to protect against the development of the other two diseases. The data presented here serve evidence for the need of haplotype analysis instead of just single standing SNP analysis when susceptibility to or protection against a certain disease are interpreted.
[show abstract][hide abstract] ABSTRACT: The involvement of B cells, complement activation and subsequent immune complex deposition has all been implicated in the pathogenesis of rheumatoid arthritis (RA). Although the reduced expression of complement receptor 1 (CR1, CD35) and 2 (CR2, CD21) on the B cells of RA patients is known for long, their exact role in B-cell tolerance and autoimmunity is not yet fully understood. To get a deeper insight into the possible mechanisms, we studied the expression and function of CR1 and CR2 on various subsets of B cells of healthy donors and RA patients at various stages of the disease by FACS analysis, H(3)-thymidine incorporation and ELISA. We found that CD19(+)CD27(-) naive B cells up-regulate the expression of the inhibitory CR1 during differentiation to CD19(+)CD27(+) memory B cells both in healthy donors and in RA patients, whereas the expression of the activatory CR2 is down-regulated. This clearly demonstrates that the expression of these two antagonistic complement receptors is regulated differentially during the development of human B cells, a phenomenon which may influence the maintenance of peripheral B-cell tolerance. Our functional studies show that after clustering CR1 both by its natural ligand and To5 mAb, the inhibitory function of CD35 is maintained in RA patients, despite its significantly reduced expression compared with healthy individuals. Besides blocking B-cell receptor-induced proliferation, CR1 inhibits the differentiation of B cells to plasmablasts and their Ig production. Since the reduced expression of CR1 in RA patients does not affect its inhibitory function, this receptor might serve as a new target for therapeutical interventions.
International Immunology 09/2012; · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: The coincidence of systemic autoimmune diseases and pregnancy may modify the outcome of the disease and the pregnancy due to the background immunologic and hormonal processes. The great majority of patients with autoimmune diseases are young females in their reproductive years, willing to have babies. Consequently, we have to prepare for this special situation. Our concept on childbearing in autoimmune women has changed within the last 30 years. Earlier, systemic lupus erythematosus flared in about 50% of patients during pregnancy, but the flare rate has significantly decreased recently. This improvement can be attributed to increased attention to low diseases activity at the time of conception, which might reduce to the half of the risk for flare. Tight control of patients and appropriate use of corticosteroids also contribute to the better results. The adequate use of anti-thrombotic agents resulted in a significant amelioration of pregnancy outcome in antiphospholipid syndrome. The earlier use of methotrexate and the introduction of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis have changed the natural characteristics of the disease. The increase in remission rate indirectly has beneficial effect on the number of planned and carried out pregnancies. Authors review the connection between systemic autoimmune disorders and pregnancy as well as the possibilities of medical treatment of such diseases during pregnancy.
[show abstract][hide abstract] ABSTRACT: Paget's disease is a chronic disorder of bone remodeling, characterized by an abnormal increase of osteoclast and, hence, osteoblast activity. The imbalance of bone turnover results in the formation of unhealthy and fragile bone. It also leads to impairment of adjacent joints and to a risk of various complications. Current research focuses on the elucidation of the etiologic role viral infection and predisposing genetic factors. Paget's disease is commonly discovered by chance; its suspicion is raised either by high level of alkaline phosphatase or by the X-ray of the pathological bone. Bisphosphonates have proven to be effective in controlling disease activity because they inhibit osteoclast function. Their use is recommended when bone-derived serum alkaline phosphatase is high and/or when disease localizations are highly suspected for the development of complications.
[show abstract][hide abstract] ABSTRACT: Hereby, we report the case of a 12-year-old girl developing oligoarthritis and progressing into a polyarticular form. Rheumatoid factor was positive, and juvenile idiopathic arthritis (JIA) was diagnosed. After a poor response to DMARDs, an anti-TNF agent (infliximab) was initiated, but to be discontinued due to an allergic reaction. The same complication was observed with the fully human derivative, adalimumab. At the age of 22, the patient presented septicemia with severe anemia and subsequent development of leukopenia, myocarditis with heart failure, and ANA, aSm, aSS-A, aCL positives, and nephrotic syndrome. These new clinical manifestations fulfilled the classification criteria for the diagnosis of systemic lupus erythematosus. Due to the poor therapeutic responses for both diseases, alternative medical options have to be considered, such as targeted therapy with anti-CD20 or interleukin-6 receptor antagonist monoclonal antibodies. This patient may also be a candidate for autologous hemopoietic stem cell transplantation.
Rheumatology International 05/2011; 31(5):695-8. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Celiac disease, or gluten sensitive enteropathy is a relatively common disease of the jejunum, leading to malabsorption. It is an immune mediated disease, induced by gluten on the grounds of a specific genetic makeup. After gluten exposition immune processes are induced mainly by T-cells, causing typical intestinal and extra intestinal manifestations. The diagnosis of celiac disease is based on jejunal biopsy histology and the presence of antibodies against endomysium and tissue transglutaminase. Genetically, celiac disease is associated with HLA DQ2/DQ8. Strict gluten-free diet improves the clinical, histological and serological picture and remission may be achieved. In the etiopathogenesis of celiac disease several genetic and immunological mechanisms have been recognized in the recent years. Concerning accompanying diseases/extraintestinal manifestations, several disorders have been shown, including rheumatological diseases. In celiac disease, bone metabolic changes are more frequent compared to the prevalence of inflammatory join disorders. In this review, we aim to give an overview on various aspects of the genetic and immunological processes in the pathomechanism of gluten-sensitive enteropathy and associated metabolic bone disorders.
[show abstract][hide abstract] ABSTRACT: To report the efficacy and safety of TNF-α inhibitors (etanercept and adalimumab) in a cohort of patients with JIA treated in a single paediatric rheumatological centre.
Patients with JIA under the age of 18 years, treated with TNF-α blockers at the Paediatric Rheumatologic Centre of the National Institute of Rheumatology and Physiotherapy (Budapest, Hungary) from 2002, were enrolled in an open, observational study. At baseline, patient and disease characteristics were registered. Disease activity was evaluated (before the start of the treatment and after every 3 months) according to the JIA core set of the ACR paediatric definition of improvement (ACR Pedi). Adverse events (AEs) were documented.
In all, 72 patients were evaluated. Mean (S.D.) age at onset was 5.5 (3.8) years, mean disease duration was 7.4 (3.9) years. All disease activity parameters improved significantly in the first 3 months of treatment. After 3 and 12 months of treatment, 88 and 76% of patients, respectively, achieved the criteria of the ACR Pedi 30. AEs were uncommon. After 12 months, >85% of patients continued the therapy.
Anti-TNF-α agents (etanercept and adalimumab) are effective, safe and well tolerated in JIA patients. Extension of this study for a longer follow-up period and to the patients with JIA after the age of 18 years (with validated and comparable disease activity parameters) is needed to evaluate the long-term effectiveness and safety of the TNF-α inhibitors.
[show abstract][hide abstract] ABSTRACT: Biological drugs have been used since the middle of the last century in medicine. Nowadays we are witnesses of the intensive development and wider administration of these drugs in clinical practice. Around 250 biological drugs are available and more than 350 million patients have been treated since their marketed authorization. Among the biologics there are protein based macromolecules, which mass production can be performed with the help of biotechnology. This term referring to the use of living organisms for production of molecules, was introduced by the Hungarian engineer, Károly Ereky. The present review focuses on the research, production and development of monoclonal antibodies manufactured by biotechnology. Some steps of this development have changed our immunological knowledge and the outcome of several diseases. The development of antibodies was highly recognized by two Nobel prizes. Authors detail the structure and functions of immunoglobulins, and their development, including fully human monoclonal antibodies. The RANKL inhibitor denosumab, a fully human IgG2 monoclonal antibody belongs to this latter group and it is available for treatment of osteoporosis. Authors also summarize the basic process of bone metabolism and the benefits of RANK ligand inhibition.
[show abstract][hide abstract] ABSTRACT: Disproportionate vitamin D levels may play an important role in the development of certain systemic autoimmune and rheumatic diseases. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with systemic lupus erythematosus (SLE) and to compare serological and clinical parameters in patients with different vitamin D levels from a single centre registry in Central-Eastern Europe.
A total of 177 patients with SLE were enrolled in the study. 25-Hydroxyvitamin D [25(OH)D] levels were measured by chemiluminescent immunoassay (CLIA). Autoantibody profiles, complement 3 (C3) and C4, clinical symptoms, and disease activity (using the SLE disease activity index, SLEDAI) of the patients were assessed.
Vitamin D concentration in the total SLE group investigated was 26.88 ± 13.25 ng/mL. Vitamin D levels were normal (≥ 30 ng/mL) in 18.1% of patients, insufficient (15-30 ng/mL) in 44.6%, and deficient (< 15 ng/mL) in 37.3%. The vitamin levels were significantly reduced in postmenopausal compared to premenopausal patients (p = 0.02). Patients with pericarditis (p = 0.013), neuropsychiatric diseases (p = 0.01), and deep vein thrombosis (p = 0.014) had reduced vitamin D levels. SLEDAI score was significantly increased in patients with reduced vitamin D levels (p = 0.038). Anti-double-stranded (ds)DNA autoantibody concentrations increased from normal to insufficient and further increased from insufficient to deficient patient subsets (p = 0.021). Anti-Smith antigen (anti-Sm) concentrations increased (p < 0.001), C4 levels decreased (p = 0.027), and immunoglobulin (Ig)G concentration increased (p = 0.034) in patients with reduced vitamin D levels.
Our data suggest that vitamin D deficiency in SLE may play a role in perpetuation of the disease.
Scandinavian journal of rheumatology 10/2010; 40(2):122-6. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Neuromyelitis optica (NMO, Devic's disease), an uncommon demyelinating neuro-immunological disease, can be associated with autoimmune diseases. In SLE associated forms anti-aquaporin-4 antibody positivity can help differentiating between SLE nerve system manifestation and NMO. In the literature rituximab, or immunoablative dose cyclophosphamide (CYC) was effective for the therapy resistant forms. Authors present 2 SLE overlapping NMO cases, one of them with SLE associated interstitial lung disease (ILD). In both cases neurological manifestations anticipated other SLE symptoms. Patients previously were treated with high dose corticosteroid therapy, plasmapheresis, and one of them with azathioprine, and the other one with oral CYC (which could not prevent flares). 0.5 g/m² body-surface monthly parenteral inductive CYC therapy was administered, in one patient followed by quarterly maintenance therapy. This patient completed her 18 month maintenance treatment and has been in neurological remission, but required steroid pulse and plasmapheresis for lung symptoms. The second patient had urogenital infection after the induction phase, followed by an exacerbation, requiring plasmapheresis and high dose parenteral corticosteroid treatment. After it he refused CYC therapy and has been taking azathioprine. He has no new symptoms, only residual ones. In our two patients conventional dose CYC therapy proved to be effective for NMO/SLE overlap, required only transient supportive therapy.
[show abstract][hide abstract] ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disorder involving different organs and organ systems with consequent characteristic clinical and serologic symptoms. Despite of the improvement in lupus survival, approximately 10-20% of patients do not respond to traditional immune suppressive therapies. Relapses are more frequent; e.g. after cyclophosphamide therapy diffuse proliferative nephritis flares in 1/3 of patients. Different immune competent cells and inflammatory mediators participate in the pathogenesis of SLE involving both the adaptive and innate immunity. Several pathogenic elements and mechanisms may serve as therapeutic targets, consequently. Authors summarize novel therapeutic possibilities and their mechanisms regarding the pathogenesis of SLE. Immune modulation of B and T cells, co-stimulatory pathways, cytokine network, soluble mediators and autologous hemopoietic stem cell transplantation are discussed.
[show abstract][hide abstract] ABSTRACT: Celiac disease or gluten-sensitive enteropathy is the most common disease of jejunum, leading to malabsorption. It is an immune mediated disease induced by gluten at the presence of genetic predisposition. After gluten exposition, immune processes are induced by T-cell mediation causing typical intestinal and extra intestinal manifestations. The diagnosis of celiac disease is still set up on the result of jejunal biopsy and detecting of antibodies against endomysium and tissue transglutaminase. From genetic aspect, association with HLA DQ2/DQ8 is identified in celiac disease. On a strict gluten-free diet, the clinical, histological and serological results improve and remission of accompanying diseases may be achieved. In the etiopathogenesis of celiac disease several genetic and immunological mechanisms have been recognized in recent years. Connected to the accompanying diseases, more reviews have been issued about the bone metabolic changes and less about the inflammatory join disorders. In the present work, the authors review literature data that reveal common background from both immunological and genetic aspects.
[show abstract][hide abstract] ABSTRACT: Associations have been found between ankylosing spondylitis (AS) and polymorphisms in the aminopeptidase regulator of TNFR1 shedding (ARTS1) gene. We studied the association of 5 polymorphisms within the ARTS1 gene with AS in Hungarian patients. We also investigated the prevalence of HLA-B27 subtypes in the Hungarian population.
A case-control study including 297 patients with AS and 200 sex and ethnically matched healthy controls was performed. Patients and controls were genotyped for rs27044, rs17482078, rs10050860, rs30187, and rs2287987 single-nucleotide polymorphisms using real-time polymerase chain reaction (PCR) allelic discrimination. HLA-B27 subtypes were determined with PCR sequence-specific primer (PCR-SSP) technique.
We observed a significant increase in the minor allele frequency of rs27044 (p = 0.001) in the AS group compared to controls. The minor allele frequencies of rs10050860 (p = 0.006) and rs2287987 (p = 0.002) showed a significant decrease in AS patients compared to controls. Haplotype analysis revealed association of 2 ARTS1 haplotypes with AS in the Hungarian population. We found that HLA-B*2705 was the predominant subtype in Hungarians with AS. Carriage of the G allele of rs27044 was significantly associated with the HLA-B*2705 subtype (p = 0.009) in AS patients.
We confirmed reported associations of ARTS1 gene polymorphisms with AS in a Hungarian cohort study. We found HLA-B*2705 as the predominant subtype in Hungarian AS patients in accord with other studies on Caucasian populations. Our results suggest that the ARTS1 gene variants together with HLA-B27 strongly contribute to disease susceptibility in patients with AS.
The Journal of Rheumatology 02/2010; 37(2):379-84. · 3.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated the genetic background regarding major histocompatibility complex (MHC) II alleles in patients with systemic lupus erythematosus (SLE) only, in patients with SLE with secondary antiphospholipid syndrome (SLE+SAPS), and in patients whose clinical course began as primary antiphospholipid syndrome (PAPS) and subsequently progressed to SLE (PAPS+SLE) in order to explain the phenotypical differences found in our previous study. Those with primary or secondary APS present more thrombotic and less inflammatory activity. Fetal wastage was the highest in the PAPS+SLE group. We performed human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 genotyping in 63 patients (26, 22, and 15 in SLE only, SLE+SAPS, and PAPS+SLE groups, respectively) and in 57 healthy controls, using PCR with sequence-specific primers. We found that, as reported in the literature, the occurrence of DRB1*03 and DQB1*0201 alleles was higher in SLE patients than in controls, but these alleles were rare in the PAPS+SLE group (13% in PAPS+SLE vs. 46% in the SLE only group; P = 0.044). HLA-DRB1*04 alleles were expressed frequently in both primary and secondary APS. DRB1*13, DQB1*06, and DQB1*0302 alleles were present more frequently in the PAPS+SLE patients than in the other groups, while the DQB1*0301 allele was rare. In this study we have shown that the SLE-associated DRB1*03/DQB1*02 alleles occurred frequently in our lupus patients as well as in SLE patients with secondary APS. In patients who started as PAPS and later progressed to SLE, the allele frequency was fundamentally different. Taken together, our results confirmed that the HLA-DRB1 and HLA-DQB1 profile of PAPS and SAPS is different. Therefore it is unlikely that these alleles are responsible for the partly similar phenotype of the two groups.
Annals of the New York Academy of Sciences 09/2009; 1173:545-51. · 4.38 Impact Factor