The relationships of human leukocyte antigen (HLA) and heavy chain immunoglobulin (Gm) haplotypes to disease and autoantibody expression were examined in six large kindreds, each having one or more members with primary Sjögren's syndrome. Various other autoimmune diseases and autoantibodies occurred among the 117 relatives in these families. The HLA and Gm haplotypes did not necessarily segregate persons into those with Sjögren's syndrome, other autoimmune disorders, or serologic abnormalities, but HLA alleles DR3 and DR2 occurred in significant excess in relatives with Sjögren's syndrome, irrespective of HLA haplotype. Segregation analysis suggested a Mendelian dominant genetic defect common to the many autoimmune diseases and serologic reactions that was not linked to HLA or Gm. A significant effect of female sex was also documented. These studies suggest that Sjögren's syndrome results from the interaction of several HLA-linked and non-HLA-linked genes.

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P-selectin (CD62) is a rapidly inducible cell surface adhesion molecule that is expressed on platelets and endothelial cells and mediates their interaction with leukocytes. In vitro studies have suggested that this receptor may play an important role in hemostasis and in inflammatory response to tissue injury. We report the molecular cloning and sequencing of murine cDNA for P-selectin. The lectin, epidermal growth factor (EGF)-like, transmembrane, and cytoplasmic domains are highly conserved between mouse and human, with an overall amino acid identity of 79%. To further investigate the biology of this adhesion molecule in vivo, we analyzed mRNA levels for P-selectin in mice after injection with endotoxin. Northern blot data indicate that the cellular response in vivo includes a rapid increase in the level of mRNA, presumably for new synthesis of P-selectin. The increase in mRNA is maximal at 4 hours, and turnover is relatively rapid, with levels of RNA having decreased substantially by 6 hours following stimulation with endotoxin. After administration of endotoxin, the highest levels of mRNA expression were detected in liver, lung, kidney, and heart.

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The relationships of HLA-DR and the newer DS (second D locus) B cell alloantigens (MB and MT) to the clinical and serologic expression of primary and secondary forms of Sjogren's syndrome (SS) were examined in 102 patients (86 whites and 16 blacks). Although HLA-DR3 was significantly increased in whites (25 of 50, 50%) and blacks (4 of 5, 80%) with primary SS compared with race-matched normal controls, it was not appreciably elevated in those with systemic lupus erythematosus (SLEMS, rheumatoid arthritis (RAb SS, or connective tissue diseaseSS. The MT2 specificity, however, was more strongly associated with primary SS (86% of whites and 100% of blacks) and also with SLESS and RA-SS compared with race-matched normal controls. Furthermore, MT2 was significantly increased in SLE-SS and R A S S when compared with non-sicca SLE and RA controls. Although primary and secondary SS were most strongly associated with this DS specificity (MT2), the anti-Ro (SS-A) and anti-La (SS-B) antibody responses were more closely allied to DR

P-selectin (CD62) is a rapidly inducible cell surface adhesion molecule that is expressed on platelets and endothelial cells and mediates their interaction with leukocytes. In vitro studies have suggested that this receptor may play an important role in hemostasis and in inflammatory response to tissue injury. We report the molecular cloning and sequencing of murine cDNA for P-selectin. The lectin, epidermal growth factor (EGF)-like, transmembrane, and cytoplasmic domains are highly conserved between mouse and human, with an overall amino acid identity of 79%. To further investigate the biology of this adhesion molecule in vivo, we analyzed mRNA levels for P-selectin in mice after injection with endotoxin. Northern blot data indicate that the cellular response in vivo includes a rapid increase in the level of mRNA, presumably for new synthesis of P-selectin. The increase in mRNA is maximal at 4 hours, and turnover is relatively rapid, with levels of RNA having decreased substantially by 6 hours following stimulation with endotoxin. After administration of endotoxin, the highest levels of mRNA expression were detected in liver, lung, kidney, and heart.

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