Soluble HLA-I (s-HLA-I) synthesis in systemic lupus erythematosus

Abstract

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.

Soluble major histocompatibility complex molecules in immune regulation: highlighting class II antigens

“…Regardless of the physiological levels of sMHC‐II proteins in the serum of healthy individuals, many pathological conditions including viral encephalitis, rheumatoid arthritis, pathological pregnancies, asthma, AIDS, chronic hepatitis C and acute chronic uveitis have been shown divergence of sMHC‐II levels from control values. By the same token, the reported levels of sHLA‐I in healthy individuals vary from 357 ng/ml to 1·06 μg/ml, while they significantly increase in AIDS patients, as well as in cases of rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjogren's syndrome and multiple sclerosis (MS) …”

“…By the same token, the reported levels of sHLA-I in healthy individuals vary from 357 ng/ml 20 to 1Á06 lg/ml, 29 while they significantly increase in AIDS patients, 29 as well as in cases of rheumatoid arthritis, systemic lupus erythematosus (SLE), Sjogren's syndrome and multiple sclerosis (MS). [30][31][32][33][34][35]…”

“…Rheumatoid arthritis, SLE, MS and Sjogren's syndrome have been thoroughly studied in regard to sMHC molecules. Soluble MHC-I proteins have been reported to be highly elevated in patients with RA, SLE and Sjogren's syndrome, [30][31][32][33][34] while sMHC-II have also been observed in synovial fluid of RA patients. 82 In this case, sMHC-II levels were found to increase with RA progression and reduce during treatment.…”

Immunobiology of HLA Class-Ib Molecules in Transplantation

“…Soluble HLA-Ib can be released in the circulation by three different mechanisms: exosomal shedding, alternative splicing, and proteolytic processing [91,92]. Each mechanism will produce different isoforms of sHLA-Ib, contributing to a pool of sHLA-Ib in the allograft microenvironment and circulation.…”

Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies

“…Importantly, during the course of an immune response, the sHLA-I antigens are known to inhibit cytotoxic lysis mediated by both T cells and NK cells and induce apoptosis of activated T cells [20,[54][55][56][57][58][59][60], thus supporting an immune regulatory function of sHLA-I present in the serum of SLE patients [44,[61][62][63]. The sHLA-F in circulation may emanate from activated lymphocytes.…”