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

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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.

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Authors and Affiliations

  1. Department of Surgery, Louisiana State University Health Sciences Center, P.0. Box 33932, Shreveport, LA 71130-3932, USA

    Irena Adamashvili & Donnie Aultman

  2. Department of Rheumatology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA

    Robert Wolf, Vicky Hall & Thomas Pressly

  3. Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA

    Stephen Jaffe, Alireza Minagar & Roger Kelley

  4. Renal Transplantation and Tissue Typing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

    Edgar L. Milford

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  1. Irena Adamashvili
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Adamashvili, I., Wolf, R., Aultman, D. et al. Soluble HLA-I (s-HLA-I) synthesis in systemic lupus erythematosus. Rheumatol Int 23, 294–300 (2003). https://doi.org/10.1007/s00296-003-0306-3

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  • DOI: https://doi.org/10.1007/s00296-003-0306-3

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