Association of DR3 with susceptibility to and severity of primary Sjögren's syndrome in a family study.

A study of HLA and primary Sjögren's syndrome (1 degree SS) was performed in 40 index cases and 180 relatives all of whom were Caucasian. The association of DR3 and 1 degree SS was confirmed. In probands, DR3 associated with extraglandular manifestations of 1 degree SS and homozygosity for DR3 associated with younger onset of disease. Familial clustering of 1 degree SS was evident. Definite or probable 1 degree SS (Fox criteria) occurred with a prevalence of 4.4% in the relatives, exclusively in older female first degree relatives and was associated with DR3. The relative risk was greatest in those who expressed anti-nuclear factor, rheumatoid factor or Ro and DR3. We identified a group of young females expressing some criteria for 1 degree SS and the same immunogenetic markers. They may be at risk of full expression of 1 degree SS as they become older. Milder forms of 1 degree SS were common in older relatives but not DR3 associated. 1 degree SS in males was rare and mild irrespective of immunogenetic status. Symptoms of 1 degree SS in relatives were mild or absent. Such individuals will only be identified through a family study or a community survey.