FcγRIIa polymorphism in Japanese patients with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an immune complex-mediated disease and organ damage is caused by the deposition of immune complex. Receptors which recognize the Fc portion of immunoglobulin G (FcgR) play a key role in the phagocytosis of immune complexes. As the gene encoding for FcgR of class IIa (FcγRIIa) has two allelic forms, H131 and R131, which differ in their affinity to IgG2, this polymorphism might have implications in handling immune complex. We studied the distribution of the FcγRIIa polymorphism in 90 Japanese patients with SLE. We also examined the association between FcγRIIa polymorphism and the disease activity of SLE and the histopathological findings of lupus nephritis. FcγRIIa polymorphism was determined by PCR and dot blot analysis. The allelic frequency of H131 in patients with SLE was significantly lower (H131/R131 ‘ 0.44/0.56) than that of normal controls (H131/R131 ‘ 0.62/0.38; P < 0.05). No significant association was observed between FcγRIIa polymorphism and the clinical parameters for the activity of SLE. There was no association between FcγRIIa polymorphism and the histological findings in lupus nephritis. The difference in the distribution of FcγRIIa alleles between patients with SLE and normal subjects indicates that this polymorphism is a candidate of susceptibility gene for SLE in Japanese.

Keywords

Fcg receptor IIa polymorphism systemic lupus erythematosus anti-double-strand DNA antibody serum complement SLE disease activity index (SLEDAI)

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References

Schur PH . Genetics of systemic lupus erythematosus . Lupus 1995; 4: 425–437 .

Nydegger UE , Lambert PH , Gerber H et al. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen quantitated by binding to radiolabeled C1q . J Clin Invest 1974; 54: 297–309 .

Koffler D , Agnello V , Thoburn R et al. Systemic lupus erythematosus: prototype of immunecomplex nephritis in man . J Exp Med 1971; 134(Suppl): 169S–179S .

Koffler D , Schur PH , Kunkel HG . Immunological studies concerning the nephritis of systemic lupus erythematosus . J Exp Med 1967; 126: 607–623 .

Kimberly RP , Salmon LE , Edberg JC . Receptors for immunoglobulin G, molecular diversity and implications for disease . Arthritis Rheum 1995; 38: 306–314 .

Salmon JE , Edberg JC , Kimberly RP . FcgRIII on human neutrophils. Allelic variants have functionally distinct capacities . J Clin Invest 1990; 85: 1287–1295 .

Salmon JE , Edberg JC , Brogle NL et al. Allelic polymorphism of human Fcg receptor IIA and Fcg receptor IIIB. Independent mechanisms for differences in human phagocyte function . J Clin Invest 1992; 89: 1274–1281 .

Warmerdam PAM , van de Winkel JGJ , Vlug A et al. A single amino acid in the second Ig-like domain of the human Fcg receptor II is critical for human IgG2 binding . J Immunol 1991; 147: 1338–1343 .

Warmerdam PAM , van de Winkel JGJ , Grosselin EJ et al. Molecular basis for a polymorphism of human Fcg receptor II (CD32) . J Exp Med 1990; 172: 19–25 .

10.

Clark MR , Stuart SG , Kimberly RP et al. A single amino acid distinguishes the high-responder from low responder form of Fc receptor II on human monocyte . Eur J Immunol 1991; 21: 1911–1916 .

11.

Parren PWHI , Warmerdam PAM , Boeije LCM et al. On the interaction of IgG subclasses with the low affinity FcγRIIa (CD32) on human monocytes, neutrophils, and platelets. Analysis of a functional polymorphism to human IgG2 . J Clin Invest 1992; 90: 1537–1546 .

12.

Moser KL , Neas BR , Salmon JE et al. Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees . Proc Natl Acad Sci USA 1998; 95: 14869–14874 .

13.

Tate BJ , Witort E , McKenzie IFC et al. Expression of the high responder/non-responder human FcγRIIa: analysis by PCR and transfection into FcR-COS cells . Immunol Cell Biol 1992; 70: 79–87 .

14.

Salmon JE , Millard S , Schachter LA et al. FcγRIIa alleles are heritable risk factors for lupus nephritis in African Americans . J Clin Invest 1997; 97: 1348–1354 .

15.

Duits AJ , Bootsma H , Derksen RHWM et al. Skewed distribution of IgG Fc receptor IIa (CD32) polymorphism is associated with renal disease in systemic lupus erythematosus patients . Arthriris Rheum 1995; 39: 1832–1836 .

16.

Song YW , Han CW , Kang SW et al. Abnormal distribution of Fcg receptor type IIa polymorphisms in Korean patients with systemic lupus erythematosus . Arthritis Rheum 1998; 41: 421–426 .

17.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

18.

Osborne JM , Chacko GW , Brandt JT et al. Ethnic variation in frequency of an allelic polymorphism of human FcγRIIa determined with allele specific oligonucleotide probes . J Immunol Meth 1994; 173: 207–217 .

19.

Bombardier C , Gladman DD , Urowitz MB et al. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE . Arthritis Rheum 1992; 35: 630–640 .

20.

Brenner BM , Rector FC Jr . The Kidney, 5th edn, Chap 31. WB Saunders: Philadelphia, PA , 1996, pp 1498–1596.

21.

Austin HA III , Muenz LR , Joyce KM et al. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome . Kidney Int 1984; 25: 689–695 .

22.

Emlen W . Dubois' Lupus Erythematosus. Lea & Febiger: Philadelphia, PA , 1993.

23.

Prada AE , Strife CF . IgG subclass restriction of autoantibody to solidphase C1q in membranoproliferative and lupus glomerulonephritis . Clin Immunol Immunopathol 1992; 63: 84–88 .

24.

Wisnieski JJ , Jones SM . Comparison of autoantibodies to the collagen-likeregionofC1q inhypocomplementemicurticarial vasculitissyndrome and systemic lupus erythematosus . J Immunol 1992; 148: 1396–1403 .

25.

Anderson CL , Shen L , Eicher DM et al. Phagocytosis mediated by three distinct Fcg receptor classes on human leukocytes . J Exp Med 1990; 171: 1333–1345 .

26.

Indik Z , Kelly C , Chien P et al. Human FcgRII, in the absence of other Fcg receptors, mediates a phagocytic signal . J Clin Invest 1991; 88: 1766–1771 .

27.

Frank MM , Hamburger MI , Lawley TJ et al. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus . New Engl J Med 1979; 300: 518–523 .

28.

Parris TM , Kimberly RP , Inman RD et al. Defective Fc receptor-mediated function of the mononuclear phagocyte system in lupus nephritis . Ann Intern Med 1982; 97: 526–532 .

29.

Manger K , Repp R , Spriewald BM et al. Fc gamma receptor IIa polymorphism in Caucasian patients with systemic lupus erythematosus: association with clinical symptoms . Arthritis Rheum 1998; 41: 1181–1189 .

30.

Botto M , Theodoridis E , Thompson EM et al. FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease . Clin Exp Immunol 1996; 104: 264–268 .

31.

Barley J , Blackwood A , Miller M et al. Angiotensin converting enzyme gene I/D polymorphism, blood pressure and the renin–angiotensin system in Caucasian and Afro-Caribbean peoples . J Hum Hypertens 1996; 10: 31–35 .