Soluble HLA-I (s-HLA-I) synthesis in systemic lupus erythematosus.
Our objective was to study a possible contribution of major histocompatibility complex (MHC) genes to soluble HLA-I synthesis in patients with systemic lupus erythematosus (SLE). Solid-phase enzyme-linked immunoassay (ELISA) was used to measure sHLA-I in the sera of 20 patients with SLE and 76 normal controls with known HLA phenotypes. Serial serum samples ( n=108) from the above group of patients ( n=19) were further investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Soluble HLA-I levels were abnormally higher in patients with SLE than normal controls ( P<0.0002). No complete HLA haplotype has been identified to be correlated with high or low sHLA-I secretion. Only the sera of HLA-A23- or -A24- (splits of HLA-A9) positive individuals were found to contain high sHLA-I concentrations in both populations studied. The difference between sHLA-I of HLA-A24 patients ( n=7) and HLA-A24 normal controls ( n=19) was statistically highly significant ( P<0.0079). The results suggest that HLA-A24 may confer additional risk of more severe disease expression in female patients with SLE. The data imply that SLE patients carrying 39-kDa sHLA-I have increased risk of developing renal disease. A higher prevalence of 35-37 kDa was observed in patients with mild disease. Interestingly, 44-46 kDa was the predominant molecular form of sHLA-I in SLE patients with lymphocytosis with no evidence of organ involvement. Notably, all these variations were not reflected by differences in HLA phenotypes, with the exception of HLA-A24-positive patients, in whom the 44-46-kDa form occurs consistently but not exclusively. In summary, the results show a genetic heterogeneity of SLE with MHC control of the expression of sHLA-I concentrations and possible involvement of disease-associated factors that might potentiate a specific sHLA-I molecule synthesis.
Adamashvili
Irena
I
Department of Surgery, Louisiana State University Health Sciences Center, P.0. Box 33932, Shreveport, LA 71130-3932, USA.
Wolf
Robert
R
Aultman
Donnie
D
Milford
Edgar L
EL
Jaffe
Stephen
S
Hall
Vicky
V
Pressly
Thomas
T
Minagar
Alireza
A
Kelley
Roger
R
D000328:Adult; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged
D015395:Histocompatibility Antigens Class I