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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., (© 2021 John Wiley & Sons Ltd.)

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-lβ 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-1β 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-1β 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-lβ production.

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 IL1β, 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 IL1β (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-1β (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.