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 (444·27 ± 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.