Greek Rheumatoid Arthritis Patients Research Articles

Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis.

Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis-hemolysin (HpmB), urease C (UreC), and urease F (UreF)-were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p=0.005, p<0.001, and p=0.003 and p=0.007, p=0.002, and p<0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide-which are non-cross-reactive with human tissue antigens-were observed and their significant difference compared to healthy controls (p=0.007, p<0.001, p<0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.

Analysis of SAA1 gene polymorphisms in the Greek population: rheumatoid arthritis and FMF patients relative to normal controls. Homogeneous distribution and low incidence of AA amyloidosis

Objective. To address whether or not the rarity of amyloidosis in Greek patients with rheumatoid arthritis (RA) is related to specific alleles of single nucleotide polymorphisms (SNPs) in the 5′-flanking region and the exon 3 of the SSA1 gene.Methods. The genotypes of the −13T/C SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 88 Greek patients with RA, 14 patients with familial Mediterranean fever (FMF) and 110 healthy controls. Linkage disequilibrium and haplotype frequencies involving −13T/C, 2995C/T and 3010C/T in these populations were tested and estimated, respectively.Results. The genotypic distribution and allelic frequencies were similar in all groups tested. SNPs 2995 and 3010 were in linkage disequilibrium for all study populations (p < 0.05), whereas SNP −13 was not in linkage disequilibrium with either 2995 or 3010 (p ≥ 0.05). Two major haplotypes presented in all patients with RA and FMF and controls: −13C; 2995T; 3010C (−13C; α) and −13C; 2995C; 3010T (−13C; β). The −13T allele was linked with the γ haplotype in Greek patients with RA and controls. The frequency of the −13T allele was found to be very rare in all groups tested.Conclusions. In conclusion, the rarity of the putative amyloidogenic −13T allele in Greek populations may be related to low prevalence of AA amyloidosis development in Greek RA patients.

Shared epitopes and rheumatoid arthritis: Disease associations in Greece and meta-analysis of Mediterranean European populations

Objectives: To assess the strength of the associations between HLA shared epitopes (SE) and rheumatoid arthritis (RA) susceptibility, articular disease severity, and extra-articular features in Mediterranean European populations. Methods: One hundred and seventy-four Greek RA patients and 103 controls were evaluated. Data were then included in a meta-analysis of 9 studies of Mediterranean European populations (959 RA patients and 1,405 controls). Results: In our study population, SE alleles were significantly more common in RA patients than in controls (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.4-4.3). Larsen radiologic score was predicted by SE and disease duration. SE did not increase the risk of any extra-articular manifestation. The meta-analysis showed a pooled OR of 3.7 (95% CI, 2.6-5.2) for susceptibility to RA conferred by SE (OR, 3.4 v 3.9 in Greek v non-Greek populations). Conclusions: SE determine articular destruction without increasing the risk of extra-articular manifestations. The immunogenetic associations of RA susceptibility are consistent, but their strength may depend on the SE prevalence in different ethnic groups. Semin Arthritis Rheum 31:361-370. Copyright 2002, Elsevier Science (USA). All rights reserved.

HLA-DRB1 alleles in Greek rheumatoid arthritis patients and their association with clinical characteristics.

The association of certain HLA-DRB1 alleles in Green rheumatoid arthritis (RA) patients with several features of the disease, the gender of the patient and the age at onset was investigated. This case control study includes 86 Greek RA patients and 130 healthy controls unrelated to the patients. HLA typing was performed by polymerase chain reaction (PCR) and hybridization with sequence-specific oligonucleotide (SSO) probes. HLA-DR4 was significantly increased in RA patients. The alleles *0101, *0401, *0405 and *1001 were associated with a higher risk of RA. The *0408 allele was absent from our patients. Sixty-five per cent of RA patients carried the 'sharp epitope' (SE) compared with 31.5% of controls. The risk for RA in individuals carrying a single allele positive for SE was 2.85 times higher, and for those carrying two alleles positive for SE 8.57 times higher, than in SE-negative individuals. The risk was higher in those carrying the *0401 allele, followed by *0405 and *0101, while the genotype *0401/*0404 was absent. Alleles positive for SE comprise a predisposing factor for RA at an early age, particularly in men, and are associated with positive rheumatoid factor, nodules and erosions.

A shared HLA-DRB1 sequence confers RA susceptibility in Greeks.

Previous serological studies of Greek rheumatoid arthritis (RA) patients have failed to demonstrate an association with DR4. Using sequence specific oligonucleotide typing we have identified the DRB1 alleles in panels of Greek RA patients and controls. When patient and control HLA-DRB1 frequencies were compared, significantly higher frequencies of DRB1*0101 (23.3% vs. 7.0%, odds ratio [OR] 4.0, 95% confidence intervals [CI] 1.4-12.0) and DRB1*1001 (20.9% vs. 5.8%, OR 4.3, 95% CI 1.3-13.7) were found in RA patients compared with controls. No association of DRB1*04 with RA was observed (20.9% vs. 14.0% in controls) confirming earlier reports. However DRB1*04 subtyping demonstrated a small but significant increase of DRB1*0405 in patients (14.0% vs. 3.5%, OR 4.5, 95% CI 1.1-18.9). When the frequency of individuals carrying the shared RA susceptibility epitope was compared between patients and controls it was found to be significantly higher in RA patients (60.5% vs. 22.1%, OR 5.4, 95% CI 2.4-12.0). We conclude that the shared epitope is significantly associated with RA in this population, but that it is predominantly accounted for by DRB1*0101 and DRB1*1001. Previous studies of UK RA patients have demonstrated a negative association of DR2 with disease and articular erosions. HLA-DR2 variants, DRB1*1501 and *1502 are not at reduced frequency in Greek RA patients (DRB1*1501, 14.0% in patients vs. 7.0% in controls; DRB1*1502, 7.0% in patients vs. 7.0% in controls). Genes conferring RA resistance may be in linkage disequilibrium with DR2 in UK patients. This does not appear to be the case in Greek RA patients. No association was seen between RA and HLA-DPB1 type.

Previous serological studies of Greek rheumatoid arthritis (RA) patients have failed to demonstrate an association with DR4. Using sequence specific oligonucleotide typing we have identified the DRB1 alleles in panels of Greek RA patients and controls

Previous serological studies of Greek rheumatoid arthritis (RA) patients have failed to demonstrate an association with DR4. Using sequence specific oligonucleotide typing we have identified the DRB1 alleles in panels of Greek RA patients and controls

Lack of HLA-antigen association in Greek rheumatoid arthritis patients.

One hundred and eighteen unrelated Greek patients with classic rheumatoid arthritis (RA) were tissue-typed for HLA-A, -B, -DR antigens and the frequency was compared to that of healthy controls. Greek RA patients regardless of sex, anatomical severity, seropositivity and age at disease onset are not associated with any of the HLA alloantigens tested. Only an increased prevalence, not statistically significant, was observed of the HLA-DR5 antigen in the Ro (SSA) positive RA group.