Association of homozygous deletion of the Humhv3005 and the VH3-30.3 genes with renal involvement in systemic lupus erythematosus

Abstract

To investigate whether deletion of the Humhv3005 and the homologous VH3-30.3 (both share an identical amino acid sequence) genes is associated with susceptibility and/or certain clinical manifestations of systemic lupus erythematosus(SLE), DNA from 108 Korean SLE patients and 102 healthy subjects were analysed for the status of hv3005 gene by polymerase chain reaction-enzyme-linked immunosorbent assay. This method consists of amplification of selected germline VH3 genes with biotinylated primers, efficient capture of amplicons onto streptavidin-coated wells, and quantitative typing of bound VH3 gene with diagnostic oligonucleotides. We found that deletion of the hv3005 gene (including VH3-30.3) was more frequent in SLE patients than in healthy controls (26.9 versus 11.8%, P 0.006, odds ratio 2.75). When clinical features were examined, patients with hv3005 deletion have a higher frequency of lupus nephritis (LN) (75.9 versus 44.3% for those without, P 0.004), and higher activity index [median (range), 6 (2-14) versus 4 (1-16) for those without, P 0.044] when biopsy-provenLN was studied. Collectively, our data suggest that deletion of the hv3005 and the 3-30.3 genes may predispose individual SLE patients to the development of LN.

Keywords

Hv3005 gene lupus nephritis polymorphism systemic lupus erythematosus

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References

Steinberg AD , Gourley MF , Klinman DM , Tsokos GC , Scott DE , Krieg AM. Systemic lupus erythematosus . Ann Intern Med 1991; 115: 548-559 .

Lindqvist AK , Alarcon-Riquelme ME. The genetics of systemic lupus erythematosus . Scand J Immunol 1999; 50: 562-571 .

Sullivan KE. Genetics of systemic lupus erythematosus. Clinical implications . Rheum Dis Clin N Am 2000; 26: 229-256 .

Tsao BP. Genetic susceptibility to lupus nephritis . Lupus 1998; 7: 585-590 .

Vyse TJ , Kotzin BL. Genetic susceptibility to systemic lupus erythematosus . A Rev Immunol 1998; 16: 261-292 .

Davies EJ , Snowden N , Hillarby MC et al. Mannose-binding protein gene polymorphism in systemic lupus erythematosus . Arthritis Rheum 1995; 38: 110-114 .

Linker-Israeli M , Wallace DJ , Prehn J et al. Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression . Genes Immun 1999; 1: 45-52 .

Mehrian R , Quismorio FP Jr , Strassmann G et al. Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus . Arthritis Rheum 1998; 41: 596-602 .

Mok CC , Lanchbury JS , Chan DW , Lau CS. Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus . Arthritis Rheum 1998; 41: 1090-1095 .

10.

Chen PP. Structural analyses of human developmentally regulated Vh3 genes . Scand J Immunol 1990; 31: 257-267 .

11.

Pascual V , Randen I , Thompson K et al. The complete nucleotide sequences of the heavy chain variable regions of six monospecific rheumatoid factors derived from Epstein-Barr virus-transformed B cells isolated from the synovial tissue of patients with rheumatoid arthritis. Further evidence that some autoantibodies are unmutated copies of germ line genes . J Clin Invest 1990; 86: 1320-1328 .

12.

Olee T , Yang PM , Siminovitch KA et al. Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases . J Clin Invest 1991; 88: 193-203 .

13.

Schroeder HW Jr , Hillson JL , Perlmutter RM. Early restriction of the human antibody repertoire . Science 1987; 238: 791-793 .

14.

Yang PM , Olsen NJ , Siminovitch KA et al. Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases . Proc Natl Acad Sci USA 1990; 87: 7907-7911 .

15.

Cho CS , Wang X , Zhao Y , Carson DA , Chen PP. Genotyping by PCR ELISA of a complex polymorphic region that contains one to four copies of six highly homologoushuman VH3 genes . Proc Assoc Am Phys 1997; 109: 558-564 .

16.

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 .

17.

McCluskey R. Lupus nephritis: kidney pathology. Appleton-Centry-Crofts: New York , 1975, pp 456-459.

18.

Austin HA III , Muenz LR , Joyce KM , Antonovych TT , Ballow JE. Diffuse proliferative lupus nephritis; Identification of specific pathologic features affecting renal outcome . Kidney Int 1984; 25: 689-695 .

19.

Huang DF , Siminovitch KA , Liu XY et al. Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus . J Clin Invest 1995; 95: 1766-1772 .

20.

Freedman BI , Wilson CH , Spray BJ , Tuttle AB , Olorenshaw IM , Kammer GM. Familial clustering of end-stage renal disease in blacks with lupus nephritis . Am J Kidney Dis 1997; 29: 729-732 .

21.

Akai Y , Sato H , Iwano M et al. Association of an insertion polymorphism of angiotensin-converting enzyme gene with the activity of lupus nephritis . Clin Nephrol 1999; 51: 141-146 .

22.

Koene HR , Kleijer M , Swaak AJ et al. The Fc gammaRIIIA-158F allele is a risk factor for systemic lupus erythematosus . Arthritis Rheum 1998; 41: 1813-1818 .

23.

Salmon JE , Millard S , Schachter LA et al. Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African-Americans . J Clin Invest 1996; 97: 1348-1354 .

24.

Wang AY , Poon P , Lai FM et al. Plasminogen activator inhibitor-1 gene polymorphism 4G/4G genotype and lupus nephritis in Chinese patients . Kidney Int 2001; 59: 1520-1528 .

25.

Zuniga R , Ng S , Peterson MG et al. Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited independently and are associated with systemic lupus erythematosus in Hispanic patients . Arthritis Rheum 2001; 44: 361-367 .

26.

Esdaile JM , Joseph L , Mackenzie T , Kashgarian M , Hayslett JP. The pathogenesis and prognosis of lupus nephritis: Information from repeat renal biopsy . Semin Arthritis Rheum 1993; 23: 135-148 .

27.

Kashgarian M. Lupus nephritis: lessons from the path lab . Kidney Int 1994; 45: 928-938 .

28.

Carson DA , Chen PP , Fox RI et al. Rheumatoid factors and immune networks . A Rev Immunol 1987; 5: 109-126 .

29.

Chen PP , Carson DA. New insightson the physiologicaland pathological rheumatoid factors in humans. In: Coutinho A , Kazatchkine MD (eds). Autoimmunity: physiology and disease. Wiley: New York , 1994, pp 247-266.

30.

Seligman VA , Suarez C , Lum R et al. The Fcgamma receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians . Arthritis Rheum 2001; 44: 618-625 .