Decreased sensitivity to prostaglandin and histamine in lymphocytes from normal HLA-B12 individuals: A possible role in autoimmunity

We examined the sensitivity of lymphocytes from normal subjects with HLA-B8 and B12 to inhibition by prostaglandin E ₂ (PGE ₂), histamine, and hydrocortisone. Phytohemagglutinin- and concanavalin A-stimulated cultures of peripheral blood mononuclear cells of subjects with HLA-B12 were significantly less (p < 0.001) inhibited by four concentrations of PGE ₂ (3 x 10 ^-9 to 3 x 10 ^-6 M) compared with non-HLA-B12 controls. There was a trend for subjects with HLA-B8 to be less sensitive to PGE ₂, but this difference was not significant. Indomethacin caused significantly less enhancement of mitogen-stimulated cultures of peripheral blood mononuclear cells from subjects with HLA-B12 compared with controls (p < 0.05). Concanavalin A-stimulated cultures of peripheral blood mononuclear cells from subjects with HLA-B12 were also significantly less inhibited by the addition of 10 ^-5 M histamine to the cultures (p < 0.05). There was no significant difference in sensitivity to hydrocortisone among the subjects with HLA-B8, B12, or controls, but there was a trend for HLA-B12 subjects to be less sensitive. The response in [ ³H] thymidine incorporation to three concentrations of concanavalin A and four concentrations of phytohemagglutinin was not different among the three groups of subjects. A depressed response to endogenous modulators of the immune response may explain the propensity for autoimmune disorders in subjects bearing HLA-B12.