Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition. We genotyped immunoglobulin allotypes of G1M (f,z), G2M (n+,n-), G3M (b,g) and KM (1,3) in 142 Korean patients with SLE and 200 healthy controls to investigate the role of the allotypes in SLE. The allele frequency of G1M (z) was significantly higher in patients with SLE as compared to the healthy controls (94.6% vs. 84.3%, corrected P = 0.0004, OR 3.30, 95% CI 1.71–6.88). The frequency of G2M (n-) allele was also higher in patients with SLE (95.3% vs. 88.3%, corrected P = 0.008, OR = 2.71, 95% CI 1.38–5.72). Distribution of the tested allele frequencies for G3M and KM were not different between the patients and controls. In the respect of antibody production, there was increased genotype frequency of G1M (z/z) in anti-Sm(-) SLE (P = 0.023 vs. control, P = 0.042 vs. anti-Sm (+) SLE). In conclusion, particular genotypes at G1M (f,z) and G2M (n+,n-) loci are significantly associated with SLE. These immunoglobulin genes may contribute to the etiology of SLE and production of autoantibodies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hahn BH (1998) Antibodies to DNA. N Engl J Med 338:1359–1368
Tsao BP (2003) The genetics of human systemic lupus erythematous. Trends Immunol 11:595–602
Tsao BP, Grossman JM, Riemekasten G, Strong N, Kalsi J, Wallace DJ, Chen CJ, Lau CS, Ginzler EM, Goldstein R, Kalunian KC, Harley JB, Arnett FC, Hahn BH, Cantor RM (2002) Familiality and co-occurrence of clinical features of systemic lupus erythematosus. Arthritis Rheum 46:2678–2685
Pandey JP (2001) Immunoglobulin GM and KM allotypes and vaccine immunity. Vaccine 19:613–7
McGaha T, Sorrentino B, Ravetch JV (2005) Restoration of Tolerance in lupus by targeted inhibitory receptor expression. Science 307:590–593
Dugoujon JM, Cambon-Thomsen A (1995) Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmune diseases: A review. Autoimmunity 22:245–260
Whittingham S, Mathews JD, Schanfield MS, Tait BD, Mackay IR (1983) HLA and Gm genes in systemic lupus erythematosus. Tissue Antigens 21:50–57
Schur P, Pandey JP, Fedrick JA (1985) Gm allotypes in white patients with systemic lupus erythematosus. Arthritis Rheum 28:828–830
Fedrick JA, Pandey JP, Chen Z, Fudenberg HH, Ainsworth SK, Dobson RL (1983) Gm allotypes in Blacks with systemic lupus erythematosus. Hum Immunol 8:177–181
Nakao Y, Matsumoto H, Miyazaki T, Nishitani H, Takatsuki K, Kasukawa R,Nakayama S, Izumi S, Fujita T, Tsuji K (1980) IgG heavy chain allotypes (Gm) in autoimmune diseases. Clin Exp Immunol 42:20–26
Mok CC, Lau CS (2003) Lupus in Hong Kong Chinese. Lupus 12:712–22
Feng PH, Boey ML (1982) Systemic lupus erythematosus in Chinese: the Singapore experience. Rheumatol Int 2:151–154
Steinber AG, Cook CE (1981) The distribution of human immunoglobulin allotypes. Oxford University Press, New York
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Balbin M, Crubb A, Abrahamson M, Grubb R (1991) Determination of allotypes G1m (f) and G1m (z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific amplification of DNA and use of allele-specific probes. Exp Clin Immunogenet 8:88–95
Brusco A, de Lange GG, Boccazzi C, Carbonara AO (1995) Molecular characterization of G2m (n+) and G2m (n-) allotypes. Immunogenetics 42:414–417
Balbin M, Grubb A, de Lange GG, Grubb R (1994) DNA sequences specific for Caucasian G3m (b) and (g) allotypes: alloty** at the genomic level. Immunogenetics 39:187–193
Moxley G, Gibbs RS (1992) Polymerase chain reaction-based shows allelic association of Km with kappa variable segment. Genomics 13:104–108
Stenszky V, Kozma L, Szegedi G, Farid NR (1986) Interplay of immunoglobulin G heavy chain markers (Gm) and HLA in predisposing to systemic lupus nephritis. J Immunolgenet 13:11–17
Hoffman RW, Sharp GC, Irvin WS, Anderson SK, Hewett JE, Pandey JP (1991) Association of immunoglobulin Km and Gm allotypes with specific antinuclear antibodies and disease susceptibility among connective tissue disease patients. Arthritis Rehum 34:453–458
Pandey JP, Cooper GS, Treadwell EL, Gilkeson GS, St. Clair EW, Dooley MA (2001) Immunoglobulin GM and KM allotypes in systemic lupus erythematosus. Exp Clin Immunogenet 18:117–122
Singh R, Mullinax PF, Moxley G (1994) Systemic lupus erythematosus is not associated with allotypic markers of immunoglobulin kappa in Caucasians. J Rheumatol 21:839–842
Hartung K, Coldewey R, Rother E, Pirner K, Specker C, Peter HH, Kalden JR, Lakomek HJ, Deicher H, de Lange GG (1991) Immunoglobulin allotypes in systemic lupus erythematosus–results of a central European multicenter study. SLE Study Group. Exp Clin Immunogenet 8:11–15
Sarvas H, Vesterinen P, Makela O (2002) Serum IgG2 concentration is associated with Gm-allotypes of IgG2 but not with the R131H polymorphism of human Fc-gamma receptor type IIa. J Clin Immunol 22:92–97
Perneger TV (1998) What’s wrong with Bonferroni adjustments. BMJ 316:1236–1238
Acknowledgments
This work was supported in part by a grant from the Ministry of Science and Technology of South Korea through the National Research Laboratory Program for Rheumatic Diseases and in part by the U.S. Department of Energy Cooperative Agreement DE-FC02-02CH11109.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00296-006-0236-y
Rights and permissions
About this article
Cite this article
Lee, E.B., Lee, Y.J., Shin, D.H. et al. Immunoglobulin GM and KM genotypes in Korean patients with systemic lupus erythematosus. Rheumatol Int 27, 219–224 (2007). https://doi.org/10.1007/s00296-006-0192-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-006-0192-6