[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoinflammatory joint disease which leads to the destruction of joints and disability of the patients. Anti-tumour necrosis factor (anti-TNF) drugs can halt radiological progression better than conventional DMARDs even in clinical non-responders.
[Show abstract][Hide abstract] ABSTRACT: Biological drugs revolutionized the treatment of inflammatory rheumatic diseases. Access to treatment presents substantial variability across Europe. The economic level of a particular country as well as administrative restrictions have been proved as determining factors of biological drug uptake. The objective of this paper was to provide an overview of biological treatment in six selected Central and Eastern European (CEE) countries, namely in the Bulgaria, Czech Republic, Hungary, Poland, Romania and Slovakia. The literature is summarized with regard to the epidemiology, disease burden and use of biological agents in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Moreover, an estimate is provided on the prevalence and number of patients with biological treatment based on international and local sources. In view of the limited availability of information and uncertainty in data, there is an urgent need for development of systematic and comprehensive data collection in inflammatory rheumatic diseases in CEE countries.
The European Journal of Health Economics 05/2014; · 2.10 Impact Factor
[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 objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.
Annals of the rheumatic diseases 04/2012; 71(4):484-92. · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.
[Show abstract][Hide abstract] ABSTRACT: To prospectively evaluate the disease course and the performance of clinical, patient-reported outcome (PRO) and musculoskeletal ultrasound measures in patients with polymyalgia rheumatica (PMR).
The study population included 85 patients with new-onset PMR who were initially treated with prednisone equivalent dose of 15 mg daily tapered gradually, and followed for 26 weeks. Data collection included physical examination findings, laboratory measures of acute-phase reactants, and PRO measures. Ultrasound evaluation was performed at baseline and Week 26 to assess for features previously reported to be associated with PMR. Response to corticosteroid treatment was defined as 70% improvement in PMR on visual analog scale (VAS).
At baseline, 77% had hip pain in addition to shoulder pain and 100% had abnormal C-reactive protein or erythrocyte sedimentation rate. On ultrasound, 84% had shoulder findings and 32% had both shoulder and hip findings. Response to corticosteroid treatment occurred in 73% of patients by Week 4 and was highly correlated with percentage improvement in other VAS measures. Presence of ultrasound findings at baseline predicted response to corticosteroids at 4 weeks. Factor analysis revealed 6 domains that sufficiently represented all the outcome measures: PMR-related pain and physical function, an elevated inflammatory marker, hip pain, global pain, mental function, and morning stiffness.
PRO measures and inflammatory markers performed well in assessing disease activity in patients with PMR. A minimum set of outcome measures consisting of PRO measures of pain and function and an inflammatory marker should be used in practice and in clinical trials in PMR.
The Journal of Rheumatology 03/2012; 39(4):795-803. · 3.26 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: To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity.
A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered 'never' or 'not very often', they were asked whether they would change their practice according to the particular recommendation.
A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were 'always' and 'very often'. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations.
The results of this survey demonstrated great support of 'Treating RA to Target' recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.
Annals of the rheumatic diseases 07/2011; 70(11):1999-2002. · 8.11 Impact Factor
[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: Background and objectiveIn the last few years, the discovery of various neurotransmitter receptors on bone cells suggested that the nervous system may participate in the control of bone metabolism. However the role of nicotinic acetylcholine receptors (nAChRs) on osteoclastogenesis has not been described in detail.Materials and methodsThe authors investigated the presence of nAChR subunits by PCR on osteoclasts (OCs). OCs were defined as tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells, derived from mouse bone marrow, differentiated in the presence of receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Additionally, the authors evaluated the effects of various nAChR agonists and antagonists on osteoclastogenesis in vitro. OC markers were evaluated by quantitative PCR.ResultsPCR investigation confirmed the presence of nAChR subunits α1-9 and β1, 2 and 4 in mouse bone marrow derived OCs differentiated in the presence of RANKL and M-CSF. Nicotine dose-dependently and markedly reduced the number of OCs by 99% (inhibitory concentration (IC50): 25 μM). Nicotine also completely reduced the number of pre-OCs, defined as TRAP positive mononuclear cells. Nicotine virtually abrogated osteoclastogenesis, however, the authors observed no difference in total cell number between nicotine-treated and untreated cells; 80% of cells stained positive for CD11b at the termination of the culture suggesting a highly specific effect of nicotine on osteoclastogenesis. Addition of nicotine had no effect on very early stages of osteoclastogenesis, when cells were stimulated only in the presence of M-CSF. Specifically, the effect of nicotine was only apparent in the presence of RANKL indicating interference downstream of RANK. Indeed, when the authors performed quantitative PCR experiments the authors found that mRNA levels of the M-CSF receptor c-fms as well as RANK remained unaffected by nicotine, whereas TRAP, cathepsin-K, matrix metalloproteinase 9 as well as nuclear factor of activated T cells, cytoplasmic 1 mRNA levels were markedly reduced by nicotine. The nicotinic agonist epibatidine showed similar effects as nicotine. The non-competitive nicotinic antagonist mecamylamine when given at high doses also inhibited osteoclastogenesis, suggesting that inhibition caused by the agonists might be associated with the desensitisation of the receptor.Conclusions
The authors have shown that nAChR agonists completely block osteoclastogenesis by interfering with OC precursor differentiation in vitro. The presence of nAChRs and the effect of nAChR agonists suggest that nicotine and the cholinergic nervous system may play an important regulatory role in osteoclastogenesis.
Annals of The Rheumatic Diseases - ANN RHEUM DIS. 01/2011; 70(2).
[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.