HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is an autoimmune disease mainly mediated by the deposit of immune complexes and defects in T lymphocytes and antigen-presenting cells along with a high production of T-helper 2 cytokines. A tolerance-inducible function of nonclassical class Ib human leukocyte antigen (HLA)-G molecule in innate and adaptive cellular responses has been reported, suggesting a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene has been associated to the stability of HLA-G messenger RNA. The insertion of the 14 bp sequence seems to be associated with lower levels of soluble HLA-G (sHLA-G). The aim of this study was to evaluate the possible association of the presence of the 14 bp sequence (+14 bp) with SLE. We have HLA-G genotyped 200 SLE patients and 451 healthy control subjects (HS; Italian) and analyzed the plasma levels of sHLA-G and interleukin-10 (IL-10) in a subset of SLE patients and healthy subjects (Italian and Danish). A significant increase of the +14 bp HLA-G allele was detected in the Italian SLE patients compared with HS [P = 0.003, OR 1.44 (95% CI 1.13-1.82)]. A significant increased frequency of HLA-G +14/+14 bp and a decreased frequency of HLA-G -14/-14 bp were observed in SLE patients. There median concentration of sHLA-G was significantly lower in the plasma of SLE patients compared with that in the plasma of healthy controls (P < 0.0001). Furthermore, the results confirmed higher concentrations of IL-10-positive plasma in SLE patients. These results support a potential role for HLA-G in the susceptibility of SLE.
Rizzo
R
R
Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy. rbr@unife.it
Hviid
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Govoni
M
M
Padovan
M
M
Rubini
M
M
Melchiorri
L
L
Stignani
M
M
Carturan
S
S
Grappa
M T
MT
Fotinidi
M
M
Ferretti
S
S
Voss
A
A
Laustrup
H
H
Junker
P
P
Trotta
F
F
Baricordi
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OR
D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D003718:Denmark; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology; D007558:Italy; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020871:RNA Stability / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000936:Antigen-Antibody Complex; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C508609:IL10 protein, human; D012333:RNA, Messenger; D016753:Interleukin-10