IMMUNOGENETICS OF RHEUMATOID-ARTHRITIS AND PRIMARY SJOGRENS-SYNDROME - DNA POLYMORPHISM OF HLA CLASS-II GENES

We investigated the DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatability Complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DFB in 24 patients with rheumatoid arthritis (RA), in 19 patients with primary Sjogren's syndrome (primary SS), and healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in RA when compared to normal controls: DRB1*04 (DR4) (relative risk, RR = 7.4, P < 10(-3)), DRB4*0101 (DRw53) (RR = 9.6, P < 10(-3)), DQA1*0301 (RR = 9.6, P < 10(-3)), DQB1*0301 (DQw7) (RR = 2.8, P < 0.05, 'corrected' P < 0.05), and DQB1*0302 (DQw8) (RR = 4.5, P < 10(-2)). Negative associations were found between RA and DRB1*1501 (DR2/DR15) (RR = 0.2, P < 10(-2)) and DQB1*0602 (DQw6) (RR = 0.2, P < 10(-2), 'corrected' P < 0.05). The frequencies in RA of other HLA class II associated DNA fragments including DPA and DPB and the antigens DPw1-w6 defined by primed lymphocyte stimulation, did not differ significantly from those in controls. In primary SS, the frequency of HLA-B8 was significantly increased (RR = 9.0, P < 10(-3)). Positive associations were found between primary SS and DNA fragments associated with DRB1*03/13 (RR = 6.8, P < 10(-3)), DRB3*0101 (DRw52) (RR = 5.7, P < 10(-2)), DQA1*0501 (RR = 6.8, P < 10(-3)), DQB1*0201 (DQw2) (RR = 11.6, P < 10(-5)), and DQB1*0602 (DQw6) (RR = 2.7, P < 0.05, 'corrected' P > 0.05). A weak, statistically insignificant association was found between primary SS and DRB1*1501 (DR2/DRw15) and the frequency of DPA1*0101 was increased (RR = 3.5) but this association did not reach significance after 'correction' of the P-value. The frequencies in primary SS of other HLA class II associated fragments including DPA and DPB and the immunologically defined antigens DPw1-w6 did not differ significantly from those in controls.