Human leukocyte antigen-G (HLA-G) is a nonclassical class I major histocompatibility complex molecule which is induced at the course of inflammatory pathologies, and its expression has been suggested as a possible mechanism of tissue protection against autoimmune inflammatory responses, therefore acting as a mechanism of immune surveillance. We investigated the influence of the 14 bp polymorphism of the HLA-G gene on systemic lupus erythematosus (SLE) by analyzing 293 patients with SLE and 460 healthy controls. The patient’s group was not in Hardy–Weinberg equilibrium, presenting an excess of heterozygotes (P = 0.014). The heterozygote group exhibited lower systemic lupus erythematosus disease activity indexes than the homozygous deletion group and the homozygous insertion group (mean value = 2.29 against 2.97 and 3.4, respectively, P = 0.035). Photosensitive patients showed a higher frequency of heterozygotes and an equivalent lower frequency of homozygotes for deletion; on the other hand, patients without arthritis presented a higher frequency of heterozygotes than the arthritis group and also a lower frequency of the del/del genotype. Overall, our results support the idea of a role of the HLA-G insertion/deletion polymorphism and therefore a role for the HLA-G molecule, on the pathology of SLE.
1 LeMaoult J Le Discorde M Rouas-Freiss N . Biology and functions of human leukocyte antigen-G in health and sickness. Tissue Antigens2003; 62: 273–284.
2.
2 Wiendl H Behrens L Maier S Johnson MA Weiss EH Hohlfeld R . Muscle fibers in inflammatory myopathies and cultured myoblasts express the nonclassical major histocompatibility antigen HLA-G. Ann Neurol2000; 48: 679–684.
3.
3 Aractingi S Briand N Le Danff C . HLA-G and NK receptor are expressed in psoriatic skin: a possible pathway for regulating infiltrating T cells. Am J Pathol2001; 159: 71–77.
4.
4 Wiendl H Feger U Mittelbronn M . Expression of the immune-tolerogenic major histocompatibility molecule HLA-G in multiple sclerosis: implications for CNS immunity. Brain2005; 128: 2689–2704.
5.
5 Torres MI Le Discorde M Lorite P . Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn’s disease. Int Immunol2004; 16: 579–583.
6.
6 Carosella ED Moreau P Aractingi S Rouas-Freiss N . HLA-G: a shield against inflammatory aggression. Trends Immunol2001; 22: 553–555.
7.
7 Wiendl H Mitsdoerffer M Weller M . Express and protect yourself: the potential role of HLA-G on muscle cells and in inflammatory myopathies. Hum Immunol2003; 64: 1050–1056.
8.
8 Verbruggen LA Rebmann V Demanet C De Cock S Grosse-Wilde H . Soluble HLA-G in Rheumatoid Arthritis. Hum Immunol2006; 67: 561–567.
9.
9 Rosado S Perez-Chacon G Mellor-Pita S . Expression of human leukocyte antigen-G in systemic lupus erythematosus. Hum Immunol2008; 69: 9–15.
10.
10 Rizzo R Hviid TV Govoni M . HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus. Tissue Antigens2008; 71: 520–529.
11.
11 Rousseau P Le Discorde M Mouillot G Marcou C Carosella ED Moreau P . The 14-bp deletion-insertion polymorphism in the 3' UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol2003; 64: 1005–1010.
12.
12 Rebmann V van der Ven K Passler M Pfeiffer K Krebs D Grosse-Wilde H . Association of soluble HLA-G plasma levels with HLA-G alleles. Tissue Antigens2001; 57: 15–21.
13.
13 Hviid TV Rizzo R Christiansen OB Melchiorri L Lindhard A Baricordi OR . HLA-G and IL-10 in serum in relation to HLA-G genotype and polymorphisms. Immunogenetics2004; 56: 135–141.
14.
14 Tripathi P Abbas A Naik S Agrawal S . Role of 14-bp deletion in the HLA-G gene in the maintenance of pregnancy. Tissue Antigens2004; 64: 706–710.
15.
15 Hviid TV Hylenius S Hoegh AM Kruse C Christiansen OB . HLA-G polymorphisms in couples with recurrent spontaneous abortions. Tissue Antigens2002; 60: 122–132.
16.
16 Hviid TV Hylenius S Lindhard A Christiansen OB . Association between human leucocyte antigen-G and success of in vitro fertilization and pregnancy outcome. Tissue Antigens2004; 64: 66–69.
17.
17 Hylenius S Andersen AMN Hviid TV . Association between HLA-G genotype and risk of preeclampsia: a case±control study using family triads. Mol Hum Reprod2004; 4: 237–246.
18.
18 Vianna P Dalmáz CA Veit TD Tedoldi C Roisenberg I Chies JA . Immunogenetics of pregnancy: role of a 14-bp deletion in the maternal HLA-G gene in primiparous pre-eclamptic Brazilian women. Hum Immunol2007; 68: 668–674.
19.
19 Hviid TV Milman N Hylenius S Jakobsen K Jensen MS Larsen LG . HLA-G polymorphisms and HLA-G expression in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis2006; 23: 30–37.
20.
20 Veit TD Vianna P Scheibel I . Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile idiopathic arthritis and rheumatoid arthritis. Tissue Antigens2008; 71: 440–446.
21.
21 Parra FC Amado RC Lambertucci JR Rocha J Antunes CM Pena SD . Color and genomic ancestry in Brazilians. Proc Natl Acad Sci U S A2003; 100: 177–182.
22.
22 Vargas AE Marrero AR Salzano FM Bortolini MC Chies JA . Frequency of CCR5delta32 in Brazilian populations. Braz J Med Biol Res2006; 39: 321–325.
23.
23 Tan EM Cohen AS Fries JF . The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1982; 25: 1271–1277.
24.
24 Bombardier C Gladman DD Urowitz MB Caron D Chang CH . Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum1992; 35: 630–640.
25.
25 Gladman D Ginzler E Goldsmith C . The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum1996; 39: 363–369.
26.
26 Lahiri DK Nurnberger JI . A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res1991; 19: 5444.
28 Mendes-Junior CT Castelli EC Simões RT Simões AL Donadi EA . HLA-G 14-bp polymorphism at exon 8 in Amerindian populations from the Brazilian Amazon. Tissue Antigens2007; 69: 255–260.
29.
29 Gazit E Slomov Y Goldberg I Brenner S Loewenthal R . HLA-G is associated with pemphigus vulgaris in Jewish patients. Hum Immunol2004; 65: 39–46.
30.
30 La Nasa G Littera R Locatelli F . The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia. Br J Haematol2007; 139: 284–288.
31.
31 Aldrich C Wambebe C Odama L Di Rienzo A Ober C . Linkage disequilibrium and age estimates of a deletion polymorphism (1597ΔC) in HLA-G suggest non-neutral evolution. Hum Immunol2002; 63: 405–412.
32.
32 Zandman-Goddard G Shoenfeld Y . Infections and SLE. Autoimmunity2005; 38: 473–485.
33.
33 Tan Z Shon AM Ober C . Evidence of balancing selection at the HLA-G promoter region. Hum Mol Genet2005; 14: 3619–3628.
34.
34 Ober C Rosinsky B Grimsley C van der Ven K Robertson A Runge A . Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A. J Reprod Immunol1996; 32: 111–123.
35.
35 Morales P Corell A Martinez LJ . Three new HLA-G alleles and their linkage disequilibria with HLA-A. Immunogenetics1993; 38: 323–331.
36.
36 Karhukorpi J Ikaheimo I Silvennoinen-Kassinen S Tiilikainen A . HLA-G polymorphism and allelic association with HLA-A in a Finnish population. Eur J Immunogenet1996; 23: 153–155.
37.
37 Hviid TV Christiansen OB . Linkage disequilibrium between human leukocyte antigen (HLA) class II and HLA-G–possible implications for human reproduction and autoimmune disease. Hum Immunol2005; 66: 688–699.
38.
38 Price P Witt C Allcock R . The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases. Immunol Rev1999; 167: 257–274.
