The HLA–DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture

To determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome-wide) genetic admixture from the European population

Perinatal and early childhood risk factors associated with rheumatoid factor positivity in a healthy paediatric population

OBJECTIVE: To examine perinatal and childhood risk factors for the presence of rheumatoid factor in healthy children. METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) is a longitudinal study of children at increased risk of type 1 diabetes, based on possession of human leucocyte antigen (HLA)‐DR4 and DR3 alleles or a family history of diabetes. 651 children who participated in DAISY, with an average age of 6.4 (range 1–15) years, were tested for the presence of rheumatoid factor in their most recent serum sample. 23 children were positive for rheumatoid factor. Exposure data were collected prospectively by interview. HLA‐DR4 alleles were identified using polymerase chain reaction‐based Class II genotyping. RESULTS: While exploring risk factors for rheumatoid factor positivity in a multivariate model, several important interaction terms involving HLA‐DR4 status suggested the need to evaluate risk factors in HLA‐DR4‐positive and HLA‐DR4‐negative children separately. In HLA‐DR4‐negative children, rheumatoid factor‐positive infants were less likely to have been breast fed for >3 months (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04 to 0.99), more likely to have been exposed to non‐parental tobacco smoke (OR 5.38; 95% CI 0.93 to 31.27) and more likely to be a race/ethnicity other than non‐Hispanic white (OR 6.94; 95% CI 1.10 to 43.88) compared with rheumatoid factor‐negative children, after adjusting for age, sex and maternal education. In HLA‐DR4‐positive children, there were no significantly associated risk factors for rheumatoid factor positivity. CONCLUSIONS: Risk factors for rheumatoid factor positivity in children vary by HLA‐DR4 genotype. In HLA‐DR4‐negative children, breast feeding may decrease the risk, and environmental tobacco smoke may increase the risk, of autoimmunity

Rheumatoid factor seropositivity is inversely associated with oral contraceptive use in women without rheumatoid arthritis

OBJECTIVES: To examine whether oral contraceptive use is associated with the presence of serum rheumatoid factor in women of reproductive age without rheumatoid arthritis. METHODS: 304 women selected from parents of children who were at increased risk of developing type 1 diabetes were studied, because they were enriched with the human leucocyte antigen‐DR4 allele, a susceptibility marker for both type 1 diabetes and rheumatoid arthritis. Participants visited a clinic where blood was drawn for rheumatoid factor testing, and exposure data were collected via questionnaires. A medical history and joint examination were performed to rule out rheumatoid arthritis. Participants and examiners were unaware of the participants' rheumatoid factor status at the time of examination and questionnaire. RESULTS: Use of oral contraceptives at any time was inversely associated with rheumatoid factor positivity (adjusted odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07 to 0.52) independent of age, education and smoking. Smoking ⩾20 pack‐years was also associated with rheumatoid factor positivity (adjusted OR 56.38, 95% CI 4.31 to 736.98) compared with never smoking. Smoking 1–19 pack‐years was not associated with a positive rheumatoid factor. CONCLUSIONS: Our results suggest that oral contraceptive use, and possibly cigarette smoking, act early in the development of the immune dysregulation that occurs in rheumatoid arthritis