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

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\ub727 \ub1 304\ub784 U/ml) compared to controls (16\ub774 \ub1 20\ub758 U/ml) (P < 0\ub70001). The plasma levels of transforming growth factor (TGF)-\u3b2 were higher in SSc patients (18 937 \ub1 15 217 pg/ml) compared to controls (11 099 \ub1 6081 pg/ml; P = 0\ub7003), and a significant correlation was found between TGF-\u3b2 and the plasma levels of total sHLA-G (r = 0\ub765; P < 0\ub701), sHLA-G1 (r = 0\ub760; P = 0\ub7003) and HLA-G5 (r = 0\ub747; P = 0\ub702). The percentage of HLA-G-positive monocytes (0\ub798 \ub1 1\ub772), CD4+ (0\ub737 \ub1 0\ub768), CD8+ (2\ub705 \ub1 3\ub774) and CD4+ CD8+ double-positive cells (14\ub753 \ub1 16\ub788) was higher in SSc patients than in controls (0\ub711 \ub1 0\ub708, 0\ub701 \ub1 0\ub701, 0\ub701 \ub1 0\ub701 and 0\ub739 \ub1 0\ub740, respectively) (P < 0\ub70001). 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