Background Behcet’s disease (BD) is a chronic relapsing multisystemic inflammatory disease. Although the actual etiology is still unclear, BD symptoms are considered to be the resultant of genetic intrinsic factors and triggering extrinsic factors . HLA-G is a non-classical HLA-class I molecule and has multiple immunoregulatory properties. A 14 bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the level of soluble HLA-G and then to associate with certain pathological conditions, including inflammatory diseases .
Objectives The aim of this study was to investigate the HLA-G 3′UTR 14bp polymorphism and sHLA-G levels in Tunisian patients with BD.
Methods 120 patients with BD, 77 males and 43 females (mean age: 38.13±11.7 years), were recruited from the internal medicine department at Fattouma Bourguiba Hospital of Monastir in Central region of Tunisia. 168 volunteer donors were recruited as healthy controls (HC) (mean age: 30.41± 9.05 years). HLA-G 14bp deletion/insertion polymorphism was detected by PCR amplification of the target sequence followed by agarose gel electrophoresis. Serum levels of soluble HLA-G (sHLA-G) were measured for 49 patients with BD (34 inactive cases, 15 active cases) and 49 healthy controls using a commercial ELISA kit.
Results A significant decreased frequency of the +14bp HLA-G allele was detected in patients with BD compared to HC (0.36 vs 0.77, P = 0.036). A significant increased frequency of HLA-G -14/-14bp was observed in patients with BD compared to HC [0.36 vs 0.22, P = 0.022, OR 0.52 (95% CI 0.29–0.93)]. The median plasmatic concentration of sHLA-G was higher in patients with BD compared to HC without significant difference (96.4 (56.4-150.65) vs 65.1 (47-136.9) U/ml, P=0.1]. However, sHLA-G levels were significantly increased in patients with active disease [150.3 (91.4-265) U/ml] compared to patients with inactive disease [85.7 (55-1127.9) U/ml, P=0.038] and HC (P=0.044). Furthermore, our results showed that the 14bp polymorphism was significantly associated with the level of sHLA-G expression. In fact, +14/+14bp subjects had significantly lower plasmatic levels of sHLA-G compared to the group with the +14/-14bp genotype (P = 0.011) or the group of individuals +14/-14bp or -14/-14bp (P = 0.004).
Conclusions The homozygous 14pb insertion is associated with decreased plasmatic levels of sHLA-G in Tunisians. Moreover, homozygous deletions are more frequent in patients with BD compared to controls and sHLA-G levels are higher in patients with active disease, suggesting a possible involvement in the disease physiopathology.
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Hviid, T.V., et al., HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics, 2004. 56(3): p. 135-41.
Disclosure of Interest None Declared
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