CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthritis: A population-based cohort study.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co-activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (-168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.

Prevalence of Temporomandibular Joint Disorders in Patients with Ankylosing Spondylitis: A Cross-Sectional Study.

BACKGROUND: This study sought to investigate which temporomandibular disorders (TMD) can be expected in patients with ankylosing spondylitis (AS) and to determine the combined impact of these conditions on the psychological status, chronic pain, and functional disability. MATERIAL AND METHODS: A cross-sectional study composed of 30 patients between 18 and 65 years with ankylosing spondylitis was performed. The research protocol considered the evaluation of outcomes related to the ankylosing spondylitis (HLA-B27 antigen, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire - Spondylitis (HAQ-S)) and temporomandibular disorders (axis I and II of the Research Diagnostic Criteria for Temporomandibular Disorders - RDC/TMD). Descriptive analyses were applied to express the results. RESULTS: The sample presented both AS and TMD, most of them (24) were diagnosed with conventional AS (HLA-B27 positive). The BASDAI was scored as 7.70 (2.30) (high activity of AS disease). Functional disability represented by high scores of BASFI [7.00 (2.63)] and HAQ-S [1.79 (0.62)] demonstrates the severe impact of the disease on the daily routine and quality of life. According to RDC/TMD diagnostic criteria, 17 (57%) share the three groups of TMD, and 9 (30%) share two groups of TMD (Group I and III). Over 73% of the volunteers scored high levels of chronic pain (Grade III and IV) associated with a high depression scale score. The sample scored the somatization scale (with and without pain) as severe. CONCLUSION: Patients with ankylosing spondylitis presented a high prevalence of temporomandibular disorder, most of them having the degenerative forms of TMJ disease. AS and TMD cause moderate to severe chronic pain and a negative impact on psychological status and functional capacities.

Is there an Inflammation Role for MYD88 in Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease with strong genetic influence, especially upon immune response components. Several cytokines from the toll-like receptors activation pathway display recognized role for RA establishment. However, few studies have verified the role of key mediators such as MYD88 gene and its genetic variants. In the present study, we aim to evaluate the rs6853 functional single-nucleotide variation (SNV) role in RA etiopathogenesis, clinical severity status, and its impact in MYD88 mRNA levels and IL-lß protein levels. For the association study, a total of 423 RA patients and 346 health individuals, enrolled as control, from Northeast and Southeast Brazil were genotyped using specific Taqman probe. For the gene expression assays, we performed a MYD88 rs6853 genotype-guided monocyte cell culture divided into non-stimulated and lypopolysaccharides (LPS)-stimulated cells from healthy individuals. MYD88 gene expression was measured using primer specifics while IL-1ß levels were evaluated by ELISA. We observed that A allele and AA genotype were associated to an increased risk to RA development (OR = 1.60; 95% CI 1.24-2.08; p = 0.0004/OR = 2.83; 95% CI 1.25-6.41; p = 0.0152). The AA genotype exhibited lower MYD88 mRNA levels than GG genotype in non-stimulated monocyte cell culture (FC - 3.83; p = 0.003). Additionally, we verified an increase of IL-1ß levels when AA genotype non-stimulated monocytes were compared to AA genotype LPS-stimulates (p = 0.021). In summary, MYD88 rs6853 polymorphism associated to RA development in our Brazilian cohort and showed influence upon MYD88 mRNA levels' expression and IL-lß production.

Are key cytokines genetic and serum levels variations related to rheumatoid arthritis clinical severity?

This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.

IL1ß, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study.

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1ß, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953 C/T IL1ß (rs1143634), -137 G/C IL18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS-PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR = 0.58; 95% CI 0.36-0.92; p = .020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p = .021) and rs2430561 with DAS28 (p = .029) and CDAI (p = .029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p < .001) and ESR (p = .034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F = 5.497; p < .001) and ESR (F = 2.727; p = .032)). Our analysis indicated that in the studied population +3953 C/T IL-1ß (rs1143634), -137 G/C IL-18 (rs187238), -94 ins/del ATTG NFKB1 (rs28362491) and +874 T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.

Interleukin (IL)-23 Receptor, IL-17A and IL-17F Gene Polymorphisms in Brazilian Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a progressive, autoimmune disease for which the previous studies have shown that some functional polymorphisms can influence its etiology. Knowing this, the aim of this study was to investigate the association of +2199 A/C IL-23R (rs10889677), -197 G/A IL-17A (rs2275913), and +7488 A/G IL-17F (rs763780) gene polymorphisms with RA susceptibility and clinical features in a Brazilian population. A total of 127 RA patients and 134 healthy controls were recruited for the analyses of polymorphic variants. Genotyping was performed using RFLP-PCR. Logistic regression was used to analyze the genotype distribution of the polymorphisms. Individuals carrying the homozygous CC genotype for the IL-23R polymorphism seem to be at lower risk for RA development (OR 0.22; p = 0.004), as well as those carrying the variant C allele (OR 0.56; p = 0.002). For the -197 G/A IL-17A polymorphism, the wild-type genotype (GG) was significantly associated with a 3.18-fold (OR 3.18; p = 0.033) increased risk for RA. In relation to the +7488 A/G IL-17F polymorphism, no significant difference was found between RA cases and control subjects (p > 0.05). Moreover, when investigating the relationship between polymorphisms and clinical features, no evidence of an association was found. Our findings suggest that the variants +2199 A/C IL-23R and -197 G/A IL-17A could contribute to RA development in the studied population. However, larger studies are needed to fully understand this genetic predisposition.

Quality of life of patients with rheumatoid arthritis under biological therapy.

OBJECTIVE: assessing health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA), before and after treatment with biological therapy. METHODS: a longitudinal study, conducted from November 2010 to September 2011, with implementation of the instruments HAQ II (health assessment questionnaire) and SF-36 (medical outcomes short-from health survey). Barlett test, Anova, Friedman and paired t-test were performed for multiple extracts. RESULTS: 30 patients were evaluated, mean age of 47.6 (SD: 12.25) years and prevalence of females (90%). The mean score of HAQ II before treatment was 1.97, with significant reduction of up to 1.23 after six months of biological therapy (p<0.01). Most of the SF-36 domains showed significant improvement after six months of treatment (p<0.01), highlighting the social aspects, pain, physical functioning, emotional issues, vitality and physical aspects. CONCLUSION: the use of biologic therapy in patients with RA refractory to standard therapies proved to be an important pharmacological strategy for improving HRQL.

Quality of life of patients with rheumatoid arthritis under biological therapy / Qualidade de vida de portadores de artrite reumatoide em terapia biológica.

Summary Objective: assessing health-related quality of life (HRQL) in patients with rheumatoid arthritis (RA), before and after treatment with biological therapy. Methods: a longitudinal study, conducted from November 2010 to September 2011, with implementation of the instruments HAQ II (health assessment questionnaire) and SF-36 (medical outcomes short-from health survey). Barlett test, Anova, Friedman and paired t-test were performed for multiple extracts. Results: 30 patients were evaluated, mean age of 47.6 (SD: 12.25) years and prevalence of females (90%). The mean score of HAQ II before treatment was 1.97, with significant reduction of up to 1.23 after six months of biological therapy (p<0.01). Most of the SF-36 domains showed significant improvement after six months of treatment (p<0.01), highlighting the social aspects, pain, physical functioning, emotional issues, vitality and physical aspects. Conclusion: the use of biologic therapy in patients with RA refractory to standard therapies proved to be an important pharmacological strategy for improving HRQL. .

Resumo Objetivo: avaliar a qualidade de vida relacionada à saúde (QVRS) em portadores de artrite reumatoide (AR), antes e após o tratamento com terapia biológica. Métodos: estudo longitudinal, realizado no período de novembro de 2010 a setembro de 2011, com aplicação dos instrumentos HAQ II (Health Assessment Questionnaire) e SF-36 (Medical Outcomes Short-From Health Survey). Foram realizados testes de Barlett, Anova, Friedman e teste- t pareado para múltiplos extratos. Resultados: foram avaliados 30 pacientes, com idade média de 47,6 (DP: 12,25) anos e prevalência do gênero feminino (90%). A média do escore do HAQ II antes do tratamento foi de 1,97, com diminuição significativa de até 1,23 após seis meses de uso de terapia biológica (p<0,01). A maioria dos domínios do SF-36 apresentou significativa melhora após seis meses de tratamento (p< 0,01), destacando os aspectos sociais, dor, capacidade funcional, aspectos emocionais, vitalidade e aspectos físicos. Conclusão: o uso de terapia biológica em pacientes com AR, refratários aos tratamentos tradicionais, demonstrou ser uma importante estratégia farmacológica para a melhoria da QVRS. .