HLA-Cw*06 class I region rather than MICA is associated with psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which affects patients suffering from psoriasis. The genetic background especially the susceptibility loci on the short arm of the chromosome six contribute to PsA development. In our study, we looked for the role of the MICA and HLA-Cw genes polymorphisms in PsA pathogenesis. We investigated 100 PsA patients and 94 healthy Czech individuals. We found an association between HLA-Cw*06 and PsA namely PsA with psoriasis type I (age of psoriasis onset before 40 years) compared to healthy individuals (P (corrected) < 0.05, OR 2.56, CI 95% 1.33-4.76 and P (corrected) = 0.01, OR 3.03, CI 95% 1.53-5.88, respectively). The MICA-A9 allele of the transmembrane microsatelite MICA polymorphism occurred more frequently in PsA with psoriasis type II group (age of psoriasis onset after 40 years) than in controls, 58.6 versus 38.0%, respectively however, this finding did not reach a statistical significance after correction (P (corrected) = 0.085).

Treatment of lupus nephritis with cyclosporine - an outcome analysis.

BACKGROUND: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience. We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN. PATIENTS AND METHODS: A total of 31 patients (25 women, 6 men, mean age 29.5 years) were enrolled in the study. The majority had proliferative LN. The mean follow-up was 85.6 +/- 24.7 months. RESULTS: CsA was used as first-line treatment in 38.7% of patients and as second-line treatment in 61.3% of patients. Complete remission was achieved in 93.5% of patients. The relapse rate was 45.2%. The mean disease-free interval was 33 months. At the end of follow-up, a total of 67.9% of the patients were in remission. The treatment led to significant improvement in proteinuria (p = 0.001) and stabilization of renal function. CONCLUSION: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy.

Does renal function influence plasma levels of advanced glycation and oxidation protein products in patients with chronic rheumatic diseases complicated by secondary amyloidosis?

BACKGROUND: The aim of the study was to assess the contribution of carbonyl and oxidative stresses to the development of amyloidosis in patients suffering from chronic rheumatic diseases, and the potential influence of renal function to their concentrations was considered. METHODS: We investigated 17 patients with chronic rheumatological diseases and histologically proven diagnosis of AA amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other selected proinflammatory markers were measured. RESULTS: An increase in serum levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA patients and also with Co (p < 0.001 for all comparisons). AGEs positively correlated with serum creatinine (r = 0.67, p = 0.004) and negatively with glomerular filtration rate (r = -0.54, p = 0.027). We did not find a correlation between AOPP and any other assessed parameters including proteins and renal parameters. PAPP-A levels were not significantly increased in any group of patients (AA-RA, nonAA-RA) in comparison with Co. CONCLUSIONS: Increased plasma levels of AGEs and AOPP in the group of patients with AA-RA may have been partly explained by the diminished renal clearance. However, the increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III).

Information technology in clinical research in rheumatology domain.

The development of a functional clinical database of rheumatic diseases represents an essential step in the process of acquiring the necessary epidemiological and other information on disorders under study. In 1999-2005 the Institute of Rheumatology in cooperation with the EuroMISE Center has developed the Clinical database/National Register of selected systemic inflammatory rheumatic diseases inclusive of a bank of sera and DNA. Aims of this phase of the pilot research were gathering clinical, laboratory, genetic, pharmaco-and socio-economic data in a representative sample of patients with systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease; rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis. In 2002 the preset number of over 2000 registered patients had been achieved with collaboration of 34 territorial and 20 institutional rheumatologists in the whole covering the majority of the Czech Republic. Based on experiences gathered, the systems for other related studies are being developed and implemented using modern information technologies.

NFkappaB and its inhibitor IkappaB in relation to type 2 diabetes and its microvascular and atherosclerotic complications.

Nuclear factor kappa B (NFkappaB) is an important transcription factor that together with its inhibitor (IkappaB) participates in the activation of genes involved in immune responses. We examined the CA repeat polymorphism of the NFKB1 gene (encoding for NFkappaB) and A/G point variation in the 3'UTR region of the nuclear factor kappa B inhibitor alpha (NFKBIA) gene (encoding for IkappaB) in Czech and German patients with type 2 diabetes. The sample consisted of 211 patients, both with and without kidney complications, and 159 controls. Additionally, 152 patients with systemic lupus erythematosus (SLE) were genotyped for NFKBIA polymorphism. We observed a significant increase in the homozygous AA genotype of the NFKBIA gene when compared with the control group (the highest value was in diabetics without diabetic nephropathy [p(c)* = 0.0015, odds ratio = 3.59]). No differences were seen between the SLE and control groups. With regard to the polymorphism of the NFKB1 gene, we did not observe any significant differences between the groups. Since the AA genotype of the NFKBIA gene presents a risk for type 2 diabetes development but not for diabetic nephropathy alone, we believe that the NFkappaB gene polymorphism can influence the pathogenesis of diabetes mellitus and affect its complications. Negative findings relative to other inflammatory autoimmune diseases, such as SLE, suggest a specific relationship between NFkappaB and type 2 diabetes mellitus.

Some principles of the development of a clinical database/national register of selected inflammatory rheumatic diseases in the Czech Republic.

According to the World Health Organisation, rheumatic diseases are likely to go on occupying a prominent place worldwide. As to US statistics, rheumatic diseases are currently the most frequent chronic disorders and leading cause of disability. The development of functional clinical database or rheumatic diseases represents an essential condition how to acquire necessary epidemiological and other information on disorders under study. In 1999-2003, Institute of Rheumatology in cooperation with EuroMISE have developed clinical database/national register of selected systemic inflammatory rheumatic diseases inclusive of bank of sera and DNA. Aims of this phase of the pilot research have been formulated into following relevant and time borders: to gather clinical, laboratory, genetic but also pharmaco- and socio-economic data in a representative sample of patients with systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease; rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis. The data about patients entering the register are differentiated according to the disease of the patient. However, many diseases have several data in common. Therefore, a simple common data structure for examination of all monitored diseases was chosen. In 2002, the preset number of over 2000 registered patients had been achieved with collaboration of 34 territorial and 20 institutional rheumatologists in the whole covering the majority of the Czech Republic. Some first acquired information inclusive comparison with German database is demonstrated.

Soluble cytokine receptors in renal vasculitis and lupus nephritis.

BACKGROUND: The activation of various cytokines, e.g. TNFalpha, IL-1 and/or IL-6, may play an important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). The systemic effect of these cytokines may be modulated by their circulating soluble receptors. The plasma levels of cytokine receptors may thus also be markers of the activation of these cytokines. MATERIAL/METHODS: The plasma levels of TNFalpha, its soluble receptor p75 (sTNF-RII), IL-6, and the soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 patients with ANCA-positive renal vasculitis (12 active - ANCA-A, 7 in remission ANCA-R), 9 patients with active lupus nephritis (LN), and 5 healthy subjects. RESULTS: Patients with LN had increased plasma levels of TNFalpha, sTNF-RII, IL-6 and sIL-6R in comparison with controls. Patients with ANCA-A also had increased plasma levels of TNFalpha, sTNF-RII and sIL-6R in comparison with controls, but the increase in the plasma level of IL-6 was not statistically significant, due to the large standard deviation. Patients with ANCA-R had increased plasma levels of sTNF-RII in comparison to controls, but the plasma levels of TNFalpha were significantly lower in ANCA-R than in ANCA-A. While the ratio of TNFalpha to sTNF-RII was significantly lower in all groups of patients than in the controls, the ratio of IL-6 to sIL-6R was significantly increased only in LN in comparison to controls. CONCLUSIONS: While increased plasma levels of TNFalpha may be a nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are also increased in patients with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may inhibit the systemic effects of TNFalpha, but may also prolong the half-life of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is much less pronounced than that of sTNF-RII and cannot effectively block the systemic effects of IL-6.