Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and KM genes on anticentromere antibody production

Kameda, Hideto; Pandey, Janardan P.; Kaburaki, Junichi; Inoko, Hidetoshi; Kuwana, Masataka

doi:10.1136/ard.57.6.366

Cited by 28 publications

(20 citation statements)

References 29 publications

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“…GM f,z loci, too, have been implicated in autoimmune responses. 13,14 Thus, B cells carrying particular f,z allotypes on their Ig receptors may be more efficient in the uptake, processing, and subsequent presentation of hsp60-derived peptides to the collaborating T cells, resulting in anti-hsp60 autoantibody production. Although GM markers are constant-region determinants, they can influence immune responsiveness, normally associated with the variable-region, in several ways: direct contribution to the formation of idiotypic determinants, modulation of antibody binding affinity, linkage disequilibrium with alleles coding for the variable-region epitopes.…”

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confidence: 99%

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

et al. 2004

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Immunoglobulin GM and KM genes have been associated with antibody responses to a variety of antigens. A promoter-region polymorphism of interleukin-6 (IL-6) gene (À174 G/C) has been shown to be associated with antibody responses to heat-shock proteins (hsp) 60 and hsp65. To examine the possible epistatic effects of these unlinked genetic systems on the autoimmune responses to hsp60 and hsp65, 176 healthy Caucasian subjects from Finland were genotyped for several allelic determinants of GM, KM, and IL-6 genes by PCR-RFLP methods. IgG antibodies to hsp60 and hsp65 were measured by an ELISA. Significant interactive effects of GM f,z and IL-6-174 genotypes were noted for both anti-hsp60 (P¼0.002) and anti-hsp65 (P¼0.038) antibody levels. Since these autoantibodies have been implicated in susceptibility to coronary heart disease and carotid atherosclerosis, the associations reported here might be relevant to the etiology of these diseases.

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confidence: 99%

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

et al. 2004

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“…Evidence for such epistatic interactions in SSc has been presented elsewhere. 15 In addition to the possible influence of IL-10 genes (via their gene products) on SSc pathogenesis discussed above, the observed associations could also be explained by linkage disequilibrium between the IL-10 alleles and those of another, as yet unidentified, locus for SSc. Such case-control studies cannot distinguish between the two possibilities.…”

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confidence: 93%

“…These include human leukocyte antigens (HLA), fibrillin-1, and GM and KM allotypes-genetic markers of g and k chains, respectively. [13][14][15] To determine if allelic variation at IL-10 loci is associated with SSc and SSc-related humoral autoimmune responses, DNA samples from Caucasian and Japanese patients and controls were genotyped at three IL-10 sites (À3575, À2849, and À2763) and patients' sera were characterized for disease-related autoantibodies.…”

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confidence: 99%

Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses

et al. 2005

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Systemic sclerosis (SSc; scleroderma) is a connective tissue disease, characterized by fibrotic, immunological, and vascular abnormalities. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that modulates collagen production and B-cell survival. To determine if certain IL-10 genotypes are risk factors for the development of SSc and influence disease-associated autoimmune responses, 248 Caucasian and 264 Japanese SSc patients and controls were genotyped for three loci: À3575, À2849, and À2763. Sera from patients were characterized for SSc-associated autoantibodies. In Caucasians, at À3575 and À2763, the frequency of AA homozygotes was higher in patients as compared with controls (P ¼ 0.0005; P ¼ 0.002). In Japanese subjects, the frequency of AC heterozygotes at À2763 was higher, and that of CC homozygotes lower, in patients with diffuse SSc as compared to controls (P ¼ 0.04). Particular IL-10 genotypes were associated with SSc-related autoantibodies. These results suggest that IL-10 genotypes contribute to the etiology of scleroderma.

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“…12,13 For example, the gene encoding the constant region of immunoglobulin kappa light chain (IGKC) which comprises three alleles, Km 1 , Km 1,2 and Km 3 corresponding to three allotypes, Km (1), Km (2) and Km (3) and can be easily studied at the DNA level, 14 has been implicated in various autoimmune diseases. [15][16][17][18][19][20][21][22] The central role of autoantibodies in pemphigus pathogenesis and the involvement of Km allotype polymorphism in various autoimmune diseases, in particular bullous pemphigoid, another autoimmune blistering skin disease, 22 invited us to study IGKC polymorphism in pemphigus susceptibility in Tunisia and in France.…”

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confidence: 99%

Pemphigus is not associated with allotypic markers of immunoglobulin kappa

et al. 2002

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Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and KM genes on anticentromere antibody production

Cited by 28 publications

References 29 publications

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

Epistatic effects of genes encoding immunoglobulin GM allotypes and interleukin-6 on the production of autoantibodies to 60- and 65-kDa heat-shock proteins

Interleukin-10 genotypes are associated with systemic sclerosis and influence disease-associated autoimmune responses

Pemphigus is not associated with allotypic markers of immunoglobulin kappa

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