2nd Workshop Neurogenetics in Germany, Munich, October 19-21, 1995
More than 90% of Caucasian narcoleptic patients carry the human-leukocyte antigen-DR2/DQw1 (DR2), a class II marker of the major histocompatibility complex, linked to several autoimmune diseases. Cytokine secretion and T cell functions were shown to depend on the DR subtype. Therefore plasma and supernatants of mitogen stimulated peripheral blood mononuclear cells were analyzed for Interleukin (IL)-2,
IL-lß, IL-lra, IL-6, TNF and TNFß. Furthermore, we did mitogen dependent proliferation assays, natural killer (nk) assays and lymphocyte subset typing. We investigated 6 male and 3 female patients each matched for sex and age with one DR2 positive and negative control. All data were analyzed by analyses of variance (ANOVA) and by t-test for comparisons between particular groups.
In vitro secretion of IL-6 by lipopolysaccharide (LPS) stimulated monocytes but not by phytohaemagglutinine (PHA) stimulated lymphocytes was significantly higher in narcoleptic patients as compared to DR2 positive controls (ANOVA F=3.12, p=0.064; t-test t=2.65, p=0.018) while there was no significant difference as compared to DR2 negative controls. The plasma levels of IL-6 showed the same trend (ANOVA F=2.34, p=0.124; t-test t=1.97, p=0.070). T cell targeting mitogen PHA stimulated proliferation of peripheral blood mononuclear cells (PMN) as well as T and B cell targeting tetanustoxin (TT) stimulated proliferation of PMN demonstrated no differences between the three groups. For lymphocyte subset typing, nk assays and all the other cytokine parameters no conclusive differences between groups emerged, either.
The results of the present investigation suggest that in narcoleptic patients monocytic functions may be altered while there is no evidence for altered T cell function.
human-leukocyte antigen-DR2/DQw1 (DR2)
interleukin-6 secretion capacity