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We studied allotypes of the fourth component of complement (C4) and factor B in 76 patients with Sjogren's syndrome (SS) and in 63 normal subjects. C4A-null (C4AQ0) was found in 10 of 28 patients who had primary SS, compared with 1 of 63 control subjects (P less than 0.005). In contrast, no significant difference in the frequency of any C4 allotype was observed between patients with secondary SS and control subjects. An association of HLA-DRw53 with primary SS in Japanese patients has been reported. Since there is no linkage disequilibrium between DRw53 and C4AQ0, it is possible that at least 2 genes in the major histocompatibility complex may determine susceptibility to the development of primary SS in the Japanese population.

Japanese patients with primary Sjogren's syndrome (SS), patients with SS and rheumatoid arthritis (SS-RA), and patients with SS and connective tissue disease without RA (nonrheumatoid connective tissue disease [SS-CTD]) were typed for HLA antigens. Patients with primary SS and those with SS-RA had higher frequencies of DRw53 than did those who had SS-CTD; however, the group with SS-CTD showed a negative correlation with DRw52. These data indicate that Japanese and white patients with SS have different HLA specificities, and that genetic factors involved in the development of SS-CTD might be different from those in primary SS and SS-RA.