The clinical course of 48 patients with primary Sjögren's syndrome (primary SS) was reviewed. Forty-three north European patients were typed for HLA class I and class II alloantigens. In this population with primary SS HLA B8, DR3 and DRw52 all occurred more frequently than in the control population (P < 0.009, P < 0.0035, P < 0.02 respectively). The subgroup of primary SS patients with antibodies to Ro and/or La antigen had the greatest prevalence of DR3 (relative risk 33.4). The primary SS patients fall into two distinct groups: those with extraglandular disease in whom lymphopaenia, hypergammaglobulinaemia, antibodies to Ro and/or La and HLA DR3 were all more frequent and those patients with either glandular disease alone or only one extraglandular feature. There was no difference in disease duration between the two groups, although on average the latter group were 10 years older.

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SUMMARYIn patients with Sjogren's syndrome 50-90% of those who have anti-La (SS-B) in their serum are HLA-DR3 positive. To investigate the relation between DR3 and anti-La antibody production 18 healthy subjects were divided into nine pairs, each matched for age and sex, containing one DR3 positive individual and one with a different DR type. Peripheral blood mononuclear cells from each pair were cultured with varying doses of pokeweed mitogen and supernatants from nine day cultures assayed for antibodies to La, nRNP/Sm, and DNA by enzyme linked immunosorbent assay (ELISA) using purified antigens. In each case peak anti-La secretion was greater in the DR3 positive subject than in the matched DR3 negative individual; in contrast, there was no consistent difference in levels of anti-DNA or anti-nRNP/Sm secretion. This specificity of enhanced autoantibody response in healthy individuals after polyclonal activation suggests that anti-La production may be under the control of genes linked to DR3.

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