Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immunomodulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444·27 ± 304·84 U/ml) compared to controls (16·74 ± 20·58 U/ml) (P < 0·0001). The plasma levels of transforming growth factor (TGF)-β were higher in SSc patients (18 937 ± 15 217 pg/ml) compared to controls (11 099 ± 6081 pg/ml; P = 0·003), and a significant correlation was found between TGF-β and the plasma levels of total sHLA-G (r = 0·65; P < 0·01), sHLA-G1 (r = 0·60; P = 0·003) and HLA-G5 (r = 0·47; P = 0·02). The percentage of HLA-G-positive monocytes (0·98 ± 1·72), CD4+ (0·37 ± 0·68), CD8+ (2·05 ± 3·74) and CD4+CD8+ double-positive cells (14·53 ± 16·88) was higher in SSc patients than in controls (0·11 ± 0·08, 0·01 ± 0·01, 0·01 ± 0·01 and 0·39 ± 0·40, respectively) (P < 0·0001). These data indicate that in SSc the secretion and/or shedding of soluble HLA-G molecules and the membrane expression of HLA-G by peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc.