HLA-G polymorphisms and HLA-G expression in sarcoidosis

Background: The MHC class Ib molecule Human Leukocyte Antigen (HLA)-G may be important in induction and maintenance of immunological tolerance, and HLA-G expression may have a role in different cancers, in certain diseases with associations to HLA, and in organ transplantation. Sarcoidosis is a systemic granulomatous disease with unknown etiology but at the molecular level several studies have shown HLA associations. Methods: In the present study, HLA-G alleles/polymorphisms were studied in sarcoidosis patients (n = 47) and controls (n = 129) by PCR techniques and HLA-G protein expression was investigated in granulomas from sarcoidosis patients with the use of immunohistochemistry. Results: The HLA-G*010102/-G*0106 alleles were observed more often in sarcoidosis patients (39.4%) than in controls (26.4%), p = 0.025 (Fisher's exact test); however, not significant after correction (p_c = 0.15). When HLA-G expression was investigated by immunohistochemistry in granulomas from sarcoidosis patients, weak HLA-G expression was observed in only one patient. Conclusions: HLA-G alleles that include a 14-bp sequence polymorphism in exon 8 of the HLA-G gene are observed more often in sarcoidosis patients than in controls. The sequence variation may influence HLA-G mRNA stability and influence the expression of soluble isoforms of HLA-G. Only rare and weak expression of HLA-G was observed in granulomas from sarcoidosis patients. More studies are needed to further elucidate the possible role for HLA-G in sarcoidosis.