A strong association between null alleles at the C4A locus in the major histocompatibility complex and systemic sclerosis

Dc, Briggs; Welsh, Ken I.; Rs, Pereira; Black, CM

doi:10.1002/art.1780291014

Cited by 37 publications

(18 citation statements)

References 14 publications

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“…The complement system has been shown to be involved in the pathogenesis of SSc. Genetically, the null allele of C4A*Q0 was reported to have a strong association with SSc (23,24). Increased serum concentrations of C1q, C2, C5, C6, C7, C9, and factor B and a decreased concentration of C4 have been observed in patients with SSc (25).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang¹,

Matsui²,

Matsuo³

et al. 2007

Arthritis & Rheumatism

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Objective. To identify pathogenic and/or diseasespecific short peptides in sera from patients with systemic sclerosis (SSc).Methods. Serum samples from 40 patients with SSc, 30 patients with systemic lupus erythematosus, 21 patients with rheumatoid arthritis, 30 patients with osteoarthritis, and 26 healthy donors were tested. Short peptides with molecular weights of smaller than ϳ3 kd, purified from the sera by magnetic bead-based hydrophobic interaction chromatography 18, were detected and their amino acid sequences determined using matrix-assisted laser desorption ionization-time-offlight mass spectrometry. Effects of the identified peptides on fibroblasts and microvascular endothelial cells were tested using synthesized peptides and sera containing the peptides.

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Section: Discussionmentioning

confidence: 99%

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Xiang¹,

Matsui²,

Matsuo³

et al. 2007

Arthritis & Rheumatism

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“…Radiolabeling, to a specific activity of 0.3-0.5 pCi/pg, was performed using Iodobeads (Pierce Chemical, Rockford, IL). After giving written informed consent, study subjects received 3-5 pCi of '*'I-C4 intravenously, and 15-17 plasma samples were drawn into Na-EDTA at 10 minutes, 30 minutes, 60 minutes, 90 minutes, and 2 , 3,4,8,12,24,36,48, 60, 72, 96, 120, and 144 hours after injection. One-milliliter plasma aliquots were counted in a Searle Model 1285 gamma counter (T. M.…”

Section: Methodsmentioning

confidence: 99%

Metabolism of C4 and linkage analysis in a kindred with hereditary incomplete C4 deficiency

Wisnieski

Nathanson

Anderson

et al. 1987

Arthritis & Rheumatism

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We studied a kindred in which C4 deficiency had been discovered. Unlike families with total absence of C4, in this kindred C4 deficiency was found to be incomplete, autosomal dominant, not caused by null alleles, and not associated with a high incidence of systemic lupus erythematosus. The deficient state was caused by hyposynthesis of C4, not by hypercatabolism. The locus for incomplete C4 deficiency was not closely linked to the major histocompatibility complex. The abnormal autosomal dominant allele is, apparently, rare, and how it causes decreased synthesis of C4 is unknown.

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“…Several immunogenetic studies of SSc patients have been performed and associations with certain HLA class I (8-13), class II ( 12,(14)(15)(16)(17)(18)(19)(20)(21), and class III ( 13,20) antigens were reported. However, these HLA associations were not strong and were sometimes inconsistent with each other.…”

Section: Introductionmentioning

confidence: 99%

The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).

Kuwana¹,

Kaburaki²,

Okano³

et al. 1993

J. Clin. Invest.

102

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HLA class II alleles were determined using the PCR-RFLP method in Japanese systemic sclerosis (scleroderma) patients with (n = 28) or without (n = 34) anti-topoisomerase I antibodies (anti-topo I). Either the DQB1 *0601 or * 0301 allele was recognized in all anti-topo I positive patients, compared with 44% of anti-topo I negative patients (P < 0.00001, relative risk[RR] > 41) or 58% of Japanese healthy control subjects (P < 0.00001, RR > 24). Tyrosine at position 26 in the second hypervariable region in the ,81 domain of the DQB1 gene is common to these two alleles and is not present in any other known DQB1 alleles. We also examined immunoreactivities of anti-topo I positive sera to four different autoantigenic B cell epitopes of topo I molecule that were expressed as recombinant fusion proteins. One major B cell epitope, located within the region corresponding to amino acid residues 74-248, was perfectly associated with the amino acid sequence FLEDR at positions 67-71 in the j1 domain of the DRB gene. Two other epitopes, corresponding to 316-441 or 658-700, were associated with the serologically defined HLA-DR52 antigen. Patients with both FLEDR and DR52 demonstrated higher antitopo I antibody titers. These results suggest that the HLA-DR and DQ genes together control the autoimmune response to topo I in systemic sclerosis. (J. Clin. Invest. 1993. 92:1296-1301

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A strong association between null alleles at the C4A locus in the major histocompatibility complex and systemic sclerosis

Cited by 37 publications

References 14 publications

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

Metabolism of C4 and linkage analysis in a kindred with hereditary incomplete C4 deficiency

The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).

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