The genes of killer cell immunoglobulin-like receptors (KIRs), which are involved in the activation of T cells and natural killer cells, are highly variable. In recent years, the role of KIRs in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of the polymorphism of KIR genes with the susceptibility to systemic lupus erythematosus (SLE). The polymorphism of KIR genes of 93 patients with SLE together with 123 healthy donors as the control group was determined by polymerase chain reaction with sequence-specific primers. Twenty-seven novel gene combinations were found. Genotypic frequencies of KIR2DL2 (p < 0.001) and KIR2DS1 (p < 0.001) were much higher in patients with SLE than in control subjects. Individuals with two and more than two activating KIR genes were found more frequently in patients than in control subjects (80.7% versus 66.7%, p = 0.022). The results suggest that a genetic disturbance between activating and inhibitory KIR genes may be one of the key factors underlying the pathogenesis of SLE.
Chen S., Hu D., Shi X., Shen N., Gu Y., Bao C.The relationship between Thl/Th2-type cells and disease activity in patients with systemic lupus erythematosus. Chin Med J (Eng1)2000; 113: 877-880.
2.
Morimoto S., Tokano Y., Kaneko H., Nozawa K., Amano H., Hashimoto H.The increased interleukin-13 in patients with systemic lupus erythematosus: relations to other Th1-, TH2- related cytokines and clinical findings. Autoimmunity2001; 34: 19-25.
3.
Wilson MJ, Torkar M., Haude A., et al. Plasticity in the organization and sequences of human KIR/ILT gene families. Proc Natl Acad Sci USA2000 ; 97: 4778-4783.
4.
Colonna M.Immunology: Unmasking the killer’s accomplice. Nature1998; 391: 642-643.
5.
Yen JH, Moore BE, Nakajima T., et al. Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis. J Exp Med2001; 193: 1159-1167.
6.
Chen AM, Liu QP, Cui XY, et al. Study on the polymorphism of killer cell immunoglobulin like receptor (KIR) gene with systemic lupus erythematosus of North population in China. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi2008; 24: 811-813.
7.
Pellett F., Siannis F., Vukin I., Lee P., Urowitz MB, Gladman DDKIRs and autoimmune disease: studies in systemic lupus erythematosus and scleroderma . Tissue Antigens2007; 69(Suppl 1): 106-108.
8.
Hochberg MCUpdating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1997; 40: 1725.
9.
Martin MP, Nelson G., Lee JH, et al. Cutting edge: susceptibility to psoriatic arthritis: influence of activating killer Ig-like receptor genes in the absence of specific HLA-C alleles. J Immunol2002; 169: 2818-2822.
10.
National Library of Medicine (US), National Center for Biotechnology Information, Carrington M, Norman P. ‘The KIR gene cluster’, http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mono_003/ch1d1.pdf (2003).
11.
Luszczek W., Mańczak M., Cisło M., et al. Gene for the activating natural killer cell receptor, KIR2DS1, is associated with susceptibility to psoriasis vulgaris. Hum Immunol2004; 65: 758-766.
12.
Jiao YL, Ma CY, Wang LC, et al. Polymorphisms of KIRs gene and HLA-C alleles in patients with ankylosing spondylitis: possible association with susceptibility to the disease . J Clin Immunol2008; 28: 343-349.
13.
Momot T., Koch S., Hunzelmann N., et al. Association of killer cell immunoglobulin-like receptors with scleroderma. Arthritis Rheum2004; 50: 1561-1565.
14.
Van der Slik AR, Koeleman BP, Verduijn W., Bruining GJ, Roep BO, Giphart MJKIR in Type 1 Diabetes: disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects. Diabetes2003 ; 52: 2639-2642.
15.
Jones DC, Edgar RS, Ahmad T., et al. Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility. Genes Immun2006; 7: 576-582.
16.
Miyashita R. , Tsuchiya N., Yabe T., et al. Association of killer cell immunoglobulin-like receptor genotypes with microscopic polyangiitis. Arthritis Rheum2006; 54: 992-997.
17.
Murata H., Matsumura R., Koyama A., et al. T cell receptor repertoire of T cells in the kidneys of patients with lupus nephritis. Arthritis Rheum2002 ; 46: 2141-2147.
18.
Lorenz HM, Griinke M., Hieronymus T., et al. In vitro apoptosis and expression of apoptosis related molecules in lymphocytes from patients with systemic lupus erythematosus and other autoimmune disease. Arthritis Rheum1997; 40: 306-317.
19.
Crispin JC, Martínez A., de Pablo P., Velasquillo C., Alcocer-Varela J.Participation of the CD69 antigen in the T cell activation process of patients with systemic lupus erythematosus. Scand J Immunol1998; 48: 196-200.
20.
Anand A., Dean GS, Quereshi K., Isenberg DA, Lydyard PMCharacterization of CD3+CD4-CD8- (double negative) T cells in patients with systemic lupus erythematosus: activation markers. Lupus2002; 11: 493-500.
21.
Waszczykowska E., Robak E., Wozniacka A., Narbutt J., Torzecka JD, Sysa-Jedrzejowska A.Estimation of SLE activity based on the serum level of chosen cytokines and superoxide radical generation . Mediators Inflamm1999; 8: 93-100.
22.
Gigante A., Amoroso D., Ferri F., et al. Systemic lupus erythematosus and renal involvement: which role of citokines expression?Eur Rev Med Pharmacol Sci2006; 10: 223-228.
23.
Bouzahzah F. , Jung S., Craft J.CD4+ T cells from lupus-prone mice avoid antigen specific tolerance induction in vivo. J Immunol2003; 170: 741-748.
24.
Tsokos GC, Mitchell JP, Juang YTT cell abnormalities in human and mouse lupus: intrinsic and extrinsic. Curr Opin Rheumatol2003; 15: 542-547.
25.
Toloza S., Pellett F., Chandran V., Ibanez D., Urowitz M., Gladman D.Association of killer cell immunoglobulin-like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus. Lupus2008; 17: 793-798.
