Review : Decreased tumour necrosis factor-beta production in TNFB*2 homozygote: an important predisposing factor of lupus nephritis in Koreans

Abstract

Low TNF production and its association with TNF gene restriction fragment length polymorphism (RFLP) was demonstrated in (NZW/NZB) F₁ mice. However, little is known about the significance of TNF production in association with TNF gene polymorphism in human SLE. This study was designed to evaluate the role of TNF production of peripheral blood mononuclear cells (PBMC) and its association with TNFB gene polymorphism in SLE, particularly lupus nephritis. TNFB gene polymorphism was defined by PCR-NcoI RFLP. TNF productions of phytohemagglutinin (PHA)- stimulated PBMC and T cells were examined by bioassay using L929 cell line and ELISA. The PBMC stimulated by PHA from patients with SLE (n = 60) tended to secrete less amounts of TNF by bioassay (1032±184pg/ml vs 1524±224pg/ml, P=0.094), and TNF-β by ELISA (P = 0.0082) than that from normal controls (n = 38). The low TNF-α producer was more frequent in nephritis than non-nephritis (34.4% vs 7.1% respectively, P<0.01). TNF-β also revealed similar results (53.1% vs 21.4%, P<0.05). In SLE, mean production of TNF-β was decreased in TNFB*2 homozygote ( n=18) than that in TNFB*1 homozygote (n = 9) (1126.3±145 pg/ml) vs 642 ± 118.4 pg/ml, respectively, P = 0.021), whereas TNF-α production showed little difference between the two groups (710.1 ± 56.4 vs 542.4 ± 71.1 pg/ml, respectively, P = 0.149). Our results demonstrate that decreased TNF production of PBMC, which was significantly associated with TNFB*2 homozygosity, could be an important predisposing factor of lupus nephritis in Koreans.

Keywords

SLE TNFB gene TNF-beta lupus nephritis

Get full access to this article

View all access options for this article.

References

Howard PF et al. Relationship between C4 null genes, HLA-D region antigens, and genetic susceptibility to systemic lupus erythematosus in Caucasian and black Americans. Am J Med 1986; 31: 187-193.

Froneck Z. et al. Major histocompatibility complex genes and susceptibility to systemic lupus erythematosus. Arthritis Rheum 1990; 33: 1542-1553.

Arnett FC , Reveille JD

Genetics of systemic lupus erythematosus. Rheum

Clin North Am 1992; 18: 865-892.

Hong KH et al. Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans. J Rheumatol 21: 442-447.

Carrol MC et al. Linkage mapping of the human major histocompatibility complex by pulsed field gel electrophoresis. Proc Natl Acad Sci USA 1987; 84: 8235-8239.

Dunham I. et al. Molecular mapping of the human major histocompatibility complex by pulsed field gel eletrophoresis. Proc Natl Acad Sci USA 1987; 84: 7237-7241.

Webb GC , Chaplin DD Genetic variability at the human tumor necrosis factor loci. J Immunol 1990; 145: 1278-1285.

Kim TG et al. Systemic lupus erythematosus with nephritis is strongly associated with the TNFB*2 homozygote in the Korean population. Hum Immunol 1996; 46: 10-17.

Jacob CO Tumor necrosis factor alpha in autoimmunity. Pretty girl or old witch . Immunol Today 1992; 13: 122-125.

10.

Jacob CO , McDevitt HO. Tumor necrosis factor-α in murine autoimmune lupus nephritis . Nature 1988; 331: 356—358.

11.

Gordon C. et al. Chronic therapy with recombinant necrosis factor-α in autoimmune NZB/NZW F1 mice. Clin Immunol Immunopathol 1989; 52: 421-434.

12.

Messer G. et al. Polymorphic structure of the tumor necrosis factor (TNF) locus. An NcoI polymorphism in the first intron of the human TNF-β gene correlates with a variant amino acid in position 26 and a reduced level of TNF-β production. J Exp Med 1991; 173: 209-215.

13.

Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-1277.

14.

Adelman DC , Wallace DJ , Klinenberg JR Thirty-four-year delayed-onset lupus nephritis: a case report. Arthritis Rheum 1987; 30: 479-480.

15.

Hogan MM , Vogel SN Production of tumor necrosis factor by rIFN-γ- primed C3H/HeJ(Lpsd) macrophages requires the presence of lipid-A-associated peptides. J Immunol Methods 1988; 95: 99-105.

16.

Mosmann T. Rapid colormetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63.

17.

Messer G. et al. Allelic variation in the TNF-β gene does not explain the low TNF-β responses in patients with primary biliary cirrhosis. Scand J Immunol 1991; 34: 735-740.

18.

Ruddle NH Tumor necrosis factor-beta/lymphotoxin-alpha. In: Thomson (ed). Cytokine Handbook, 2nd edn. Academic Press: New York , 1994, pp 311-313.

19.

Beutler B. , Cerami A. Cachectin and tumor necrosis factor as two sides of the same biological coin . Nature 1986; 320: 584-588.

20.

Janssen O. , Kabelitz D. Tumor necrosis factor selectively inhibits activation of human B cells by Epstein-Barr virus. J Immunol 1988; 140: 125-130.

21.

Jacob CO et al. Heritable major histocompatibility complex class IIassociated differences in production of tumor necrosis factor α: relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA, 1990; 87: 1233-1237.

22.

Mitamura K. et al. Impared tumor necrosis factor-α (TNF-α) production and abnormal B cell response to TNF-α in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 1991; 85: 386-391.

23.

Watanabe Y. , Jacob CO Regulation of MHC class II antigen expression: opposing effect of TNF-α on IFN-r induced HLA-DR and la expression depends on the maturation and differentiation stage of the cell. J Immunol 1991; 146: 899-905.

24.

Leewenberg Jfm et al. Effects of tumor necrosis factor on the interferon-γ-induced major histocompatibility complex II antigen expression by human endothelial cells. Eur J Immunol 1988; 18: 1469-1475.

25.

Greenwood BM , Herrick EM , Voller A. Suppression of autoimmune disease in NZB and (NZW x NZB)F1 hybrid mice by infection with malaria. Nature 1970; 226: 266-267.

26.

Adebajo AO

Does tumor necrosis factor protect against lupus in west Africa?

Arthritis Rheum 1982; 35: 839-840.

27.

Hashimoto H. , Tsuda H. , Matsumoto T. HLA antigens association with systemic lupus erythematosus. J Rheumatol 1985; 12: 919-923.

28.

Hawkins BR et al. Strong association between major histocompatibility complex and systemic lupus erythematosus. J Rheumatol 1987; 14: 1128-1131.

29.

Bettinotti MP et al. Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus. Immunogenetics 1993; 37: 449-454.

30.

Alfonso SD , Richiardi PM A polymorphic variation in a putative regulation box of the TNFA promotor region. Immunogenetics 1994; 39: 150-154.

31.

Wilson AG et al. A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha. Eur J Immunol 1994; 24: 191-195.

32.

Pociot F. et al. No independent association between a tumor necrosis factor-α promotor region polymorphism and insulin-dependent diabetes mellitus. Eur J Immunol 1993; 23: 3043-3049.