An Immunoblotting Technique for Direct Visualization of Chido and Rodgers Reactivity on C4 Variants after Electrophoresis

Sklarin, Peter M.; Awdeh, Zuheir L.; Alper, Chester A.

doi:10.1111/j.1423-0410.1988.tb01611.x

Cited by 4 publications

References 22 publications

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Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses

et al. 1990

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Informative pedigree analysis of two rare C4 allotypes is reported. One proband was C4A deficient as a consequence of having one haplotype with a deleted C4A gene, and the second haplotype with two C4B genes--one encoding the common C4B*1 and one encoding a unique hybrid gene product C4B*3. C4B*3 had approximately normal C4B hemolytic activity, a single alpha-chain of MR 94,000 by SDS-PAGE but was positive for Rg:1,2 by hemagglutination inhibition (HAI) and for Rg:1 by Western blotting. The hybrid nature was confirmed by RFLP analysis with a Rg:1-associated fragment by Eco0109 digestion but no C4A-associated fragments by N1aIV digestion were identified. A gene conversion at Locus I which included just the C4 isotype region could explain the structure of C4B*3. The second pedigree had a Rodgers negative C4A*12 allotype. This C4A gene, which segregated with a single 7.0 kb TaqI fragment, encoded a C4A alpha-chain, which was negative for Rg:1 epitope. The affected haplotype lacked the Rg:1-associated fragment by Eco0109 digestion yet had the C4A specific N1aIV digestion fragment. These studies successfully employed RFLP analyses to confirm serologic and electrophoretic observations.

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Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses

et al. 1990

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THE ANTIGENIC DETERMINANTS, Rg/Ch/WH, EXPRESSED BY JAPANESE C4 ALLOTYPES

Giles

Tokunaga

Zhang

et al. 1988

Int J Immunogenetics

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SUMMARY The expression of antigenic determinants, Rg/Ch/WH, on Japanese C4 allotypes has been studied. Although the Japanese C4 allotype frequencies are known to differ from Europeans, the antigenic expression of their C4 allotypes correlates with associations described previously. All 89 random donors and 17 selected donors were Rg:1,2 so neither Rg:1,−2 nor Rg:−1,−2 was found. The frequency of Ch: 1,−2,3 was elevated while that of Ch: 1,2,3 was reduced, which was seen as a direct result of the higher frequency of B2 and B5 allotypes. None of the Japanese were Ch: 1,2,−3, but this can be accounted for by the absence of the A*6,B*1 haplotype. The WH determinant, which has been associated completely with Rg:1,−2 in Caucasians, was found at a higher frequency, 32%, in association with an A*3,2,B*QO haplotype expressing Rg:1,2, which has not been described previously. Detailed investigation showed that the A3 allotype was Rg:1,2 whereas the A2 allotype only expressed Rg1 (Rg:1,−2 WH+).

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The Intricate Role of Complement Component C4 in Human Systemic Lupus Erythematosus

Yang

Chung

Zhou

et al. 2003

Current Directions in Autoimmunity

130

109

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It was observed about 50 years ago that low serum complement activity or low protein concentrations of complement C4 concurred with disease activities of systemic lupus erythematosus (SLE). Complete deficiencies of complement components C4A and C4B, albeit rare in human populations, are among the strongest genetic risk factors for SLE or lupus-like disease, across HLA haplotypes and racial backgrounds. However, whether heterozygous or partial deficiency of C4A (C4AQ0) or C4B (C4BQ0) is a predisposing factor for SLE has been a highly controversial topic. In this review we critically analyzed past epidemiologic studies on deficiency of C4A or C4B in human SLE. Cumulative results from more than 35 different studies revealed that heterozygous and homozygous deficiencies of C4A were present in 40-60% of SLE patients from almost all ethnic groups or races investigated, which included northern and central Europeans, Anglo-Saxons, Caucasians in the US, African Americans, Asian Chinese, Koreans and Japanese. In addition, French SLE and control populations had relatively low frequencies of C4AQ0, but the difference between the patient and control groups was statistically significant. The relative risk of C4AQ0 in SLE varied between 2.3 and 5.3 among different ethnic groups. In Caucasian and African SLE patients, the two major causes for C4AQ0 are (1) the presence of a mono-S RCCX (RP-C4-CYP21-TNX) module with a single, short C4B gene in the major histocompatibility complex; and (2) a 2-bp insertion into the sequence for codon 1213 at exon 29 of the mutant C4A gene. Both mono-S structures and 2-bp insertion in exon 29 are absent or extremely rare in the C4AQ0 of Oriental SLE patients. The highly significant association of C4AQ0 with SLE across multiple HLA haplotypes and ethnic groups, and the presence of different mechanisms leading to a C4A protein deficiency among SLE patients suggested that deficiency or low expression level of C4A protein is a primary risk factor for SLE disease susceptibility per se. On the other hand, Spanish, Mexican, Australian Aborigine SLE patients had increased frequencies of C4B deficiency instead of C4A deficiency. Such observations underscore the importance of both C4A and C4B proteins in the fine control of autoimmunity. Different racial and genetic backgrounds could change the thresholds for the requirement of C4A or C4B protein levels in immune tolerance and immune regulation. Most past epidemiological studies of C4 in human SLE did not consider the polygenic and gene size variations of C4A and C4B. In addition, many studies were overly dependent on phenotypic observations or methods that did not distinguish differential C4A and C4B protein expression caused by unequal gene number or different gene size from the absence of a functional C4A or C4B gene. For further longitudinal studies on clinical manifestations of SLE, it would be informative to stratify the patients with accurately defined C4A and C4B genotypes. Likewise, elucidation of epistatic genetic factors interacting with C4AQ0 wou...

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An Immunoblotting Technique for Direct Visualization of Chido and Rodgers Reactivity on C4 Variants after Electrophoresis

Cited by 4 publications

References 22 publications

Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses

Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses

THE ANTIGENIC DETERMINANTS, Rg/Ch/WH, EXPRESSED BY JAPANESE C4 ALLOTYPES

The Intricate Role of Complement Component C4 in Human Systemic Lupus Erythematosus

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An Immunoblotting Technique for Direct Visualization of Chido and Rodgers Reactivity on C4 Variants after Electrophoresis

Cited by 4 publications

References 22 publications

Characterization of two hybrid C4 allotypes (C4A*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses

Characterization of two hybrid C4 allotypes (C4A*12 and C4B*3) by electrophoretic, serological and restriction fragment length polymorphism analyses

THE ANTIGENIC DETERMINANTS, Rg/Ch/WH, EXPRESSED BY JAPANESE C4 ALLOTYPES

The Intricate Role of Complement Component C4 in Human Systemic Lupus Erythematosus

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Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses

Characterization of two hybrid C4 allotypes (C4A12* and C4B3*) by electrophoretic, serological and restriction fragment length polymorphism analyses