[Rheumatology. TNF alpha-inhibitors: infection risks? Practical recommendations]. / Rhumatologie. Anti-TNF alpha: quels risques infectieux? Recommandations pratiques.

Anti-TNF alpha are immunomodulatory treatments prescribed for some rheumatologic inflammatory diseases (ex: spondylarthropathy, rheumatoid polyarthritis). The randomised studies suggested that anti-TNF alpha therapy is associated with an overall risk of infectious diseases. The results of the observational studies are more reassuring. In this article, we will describe some results of theses studies and propose some practical recommendations in use of the anti-TNF alpha therapy.

Variants of the IL23R gene are associated with ankylosing spondylitis but not with Sjögren syndrome in Hungarian population samples.

Recently, associations were found between several autoimmune diseases and functional variants of interleukin-23 receptor (IL23R) gene; here, we studied the possible association of nine polymorphisms of IL23R with ankylosing spondylitis (AS) and with Sjögren syndrome (SS). In our study, we genotyped groups of patients with AS (n = 206), SS (n = 156) and healthy controls (n = 235) for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, rs11209026, rs10489629, rs7517847 and rs7530511 variants using PCR-RFLP methods. We observed significant increase in the carriage of the T allele of rs11805303 and the A allele of rs1004189 in the AS group compared with the controls. For the rs10889677 variant, the prevalence of the AA genotype and for the rs2201841, the CC genotype showed a more than two-fold increase in the AS group compared with the controls. By contrast, the GA heterozygous genotype of rs11209026 variant showed a significant decrease in AS patients compared with controls. Haplotype analysis revealed association of four IL23R haplotypes with AS. There was no difference in the distribution of any of the examined IL23R variants between controls and SS patients. In conclusion, we confirmed the susceptibility or protective associations of IL23R polymorphisms with AS in a Hungarian population and first demonstrated the involvement of the rs11805303 intronic single nucleotide polymorphisms, which was tested so far only for other autoimmune diseases.

Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA.

Lack of genetic association of the Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms with spondylarthropathies in a Hungarian population.

OBJECTIVES: Bacteria have long been suggested as aetiological factors in the genetically susceptible host in spondylarthropathies, including ankylosing spondylitis (AS) and reactive arthritis (ReA). Variability of the Toll-like receptor 4 (TLR4) gene has been shown to play a role in the inflammatory response to certain bacterial infections. We investigated whether TLR4 Asp299Gly and Thr399Ile polymorphisms contribute to the genetic background of spondylarthropathies in a cohort of Hungarian patients with AS and ReA. METHODS: DNA was obtained from patients with AS (n=138), ReA (n=91) and ethnically matched healthy controls (n=140). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis and the results were confirmed by direct sequencing. RESULTS: No significant differences in allele or genotype frequencies were observed between controls and either the AS patients or the ReA patients. Clinical characteristics of these groups were unrelated to the presence of any of these polymorphisms. CONCLUSIONS: Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms do not contribute to disease susceptibility in either AS or ReA. Functional abnormalities of the TLR4 signalling pathway suggested in spondylarthropathies seem not to be genetically determined by these two common polymorphisms.