A Novel Immunoassay for the Quantitation of Human C4 Gene Products

Moulds, J M; Arnett, Frank C.; Giles, C G; Hamilton, Robert G.

doi:10.1159/000463134

Cited by 16 publications

(11 citation statements)

References 18 publications

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“…Eight subjects had bimodular RCCX structures from both haplotypes; among them were homozygous LL/LL (L, long) (MK1, 11, and 13), heterozygous LL/LS (S, short) (MK2, 3, and 5), and homozygous LS/LS (MK12). Of these eight individuals who each had a total of four C4 genes in a diploid genome, five had two C4A and two C4B genes (MK2, 3,8,12, and 13; Fig. 2C).…”

Section: Genotypic Variation Of Human Complement Components C4a and C4bmentioning

confidence: 99%

“…The plasma or serum protein levels of total C4 vary between 100 and 1000 mg/L among different individuals, as do the relative quantities of C4A and C4B proteins. Although this phenomenon has been observed over a decade ago (5)(6)(7)(8)(9)(10)(11)(12)(13)(14), the molecular genetic basis for the qualitative and quantitative variations of human complement C4 was often accounted for inaccurately. Until recently, the sophistication of human C4 genetics has not been fully appreciated.…”

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confidence: 99%

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Diversity in Intrinsic Strengths of the Human Complement System: Serum C4 Protein Concentrations Correlate withC4Gene Size and Polygenic Variations, Hemolytic Activities, and Body Mass Index

Yang

Chung

Zhou

et al. 2003

The Journal of Immunology

113

112

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Among the genes and proteins of the human immune system, complement component C4 is extraordinary in its frequent germline variation in the size and number of genes. Definitive genotypic and phenotypic analyses were performed on a central European population to determine the C4 polygenic and gene size variations and their relationships with serum C4A and C4B protein concentrations and hemolytic activities. In a study population of 128 healthy subjects, the number of C4 genes present in a diploid genome varied between two to five, and 77.4% of the C4 genes belonged to the long form that contains the endogenous retrovirus HERV-K(C4). Intriguingly, higher C4 serum protein levels and higher C4 hemolytic activities were often detected in subjects with short C4 genes than those with long genes only, suggesting a negative epistatic effect of HERV-K(C4) on the expression of C4 proteins. Also, the body mass index appeared to affect the C4 serum levels, particularly in the individuals with medium or high C4 gene dosages, a phenomenon that was dissimilar in several aspects from the established correlation between body mass index and serum C3. As expected, there were strong, positive correlations between total C4 gene dosage and serum C4 protein concentrations, and between serum C4 protein concentrations and C4 hemolytic activities. There were also good correlations between the number of long genes with serum levels of C4A, and the number of short genes with serum levels of C4B. Thus, the polygenic and gene size variations of C4A and C4B contribute to the quantitative traits of C4 with a wide range of serum protein levels and hemolytic activities, and consequently the power of the innate defense system.

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Section: Genotypic Variation Of Human Complement Components C4a and C4bmentioning

confidence: 99%

mentioning

confidence: 99%

Diversity in Intrinsic Strengths of the Human Complement System: Serum C4 Protein Concentrations Correlate withC4Gene Size and Polygenic Variations, Hemolytic Activities, and Body Mass Index

Yang

Chung

Zhou

et al. 2003

The Journal of Immunology

113

112

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“…Total C4 was assessed by both radial immunodif fusion (Kallestad, Austin, Tex., USA) and an EIA [10] which used HRPO-conjugated monoclonal anti-C4d for detection. The moAb used for the total C4 assay recognized an epitope found on all common C4 allo types and was not isotype specific.…”

Section: Methodsmentioning

confidence: 99%

“…C4 allotype frequencies, functional activ ity and antigenic makeup as well as genetic linkages to HLA haplotypes have been well [4][5][6][7], Several immunoassays (EIAs) using monoclonal antibodies (moAbs) are now available to quantitate C4A and C4B [8][9][10], The purpose of this study was to provide each standard sample was previously determined by both RID and rate-nephelometry. Total C4, C4A and C4B of the test samples were quantitated by interpo lating mg/dl of C4 from the standard curve.…”

Section: Introductionmentioning

confidence: 99%

Quantitative and Antigenic Differences in Complement Component C4 between American Blacks and Whites

Moulds¹,

Warner²,

Arnett³

1991

Complement Inflamm

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A population of 98 healthy Black Americans was studied in order to determine normal ranges for total C4, C4A and C4B. Mean total C4 in Blacks measured by an enzyme- linked immunoassay (EIA) was 44 ± 12.8 mg/dl which was significantly different (p < 0.001) from Caucasian levels of 31.7 ± 11.5 mg/dl. The difference in total C4 was due to increased levels of C4B in Blacks (X = 24.4 mg/dl) as compared to Whites (X = 15.7 mg/dl; p < 0.001). These results remained significantly different even when 8 samples having the C4A 91 phenotype were excluded. Since El As using monoclonal antibodies with Ch1 specificity may yield false results, C4 allotyping is recommmended when quantitating C4A and C4B levels in Blacks.

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“…C3 and C4 (C4A, C4B) levels were determined by radial immunodiffusion (47), ELISA (48), and total hemolytic complement in gels (Quantiplate; Kallestad, Beaumont, TX).…”

Section: Complement Allotyping Assay Of Protein Titers and Hla Typingmentioning

confidence: 99%

The Molecular Basis of Complete Complement C4A and C4B Deficiencies in a Systemic Lupus Erythematosus Patient with HomozygousC4AandC4BMutant Genes

Rupert

Moulds

Yang

et al. 2002

The Journal of Immunology

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The disease course of a complete C4-deficient patient in the U.S. was followed for 18 years. The patient experienced multiple episodes of infection, and he was diagnosed with systemic lupus erythematosus at age 9 years. The disease progressed to WHO class III mild lupus nephritis and to fatal CNS vasculitis at age 23 years. Immunochemical experiments showed that the patient and his sibling had complete absence of C4A and C4B proteins and were negative for the Rodgers and Chido blood group Ags. Segregation and definitive RFLP analyses demonstrated that the patient and his sibling inherited two identical haplotypes, HLA A2 B12 DR6, each of which carries a defective long C4A gene and a defective short C4B gene. PCR and DNA sequencing revealed that the mutant C4A contained a 2-bp insertion in exon 29 at the sequence for codon 1213. The identical mutation was absent in the mutant C4B. The C4B mutant gene was selectively amplified by long range PCR, and its 41 exons were completely sequenced. The C4B mutant had a novel single C nucleotide deletion at the sequence for codon 522 in exon 13, leading to frame-shift mutation and premature termination. Thus, a multiplex PCR is designed by which known mutations in C4A and C4B can be elucidated conveniently. Among the 28 individuals reported with complete C4 deficiency, 75–96% of the subjects (dependent on the inclusion criteria) were afflicted with autoimmune or immune complex disorders. Hence, complete C4 deficiency is one of the most penetrant genetic risk factors for human systemic lupus erythematosus.

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A Novel Immunoassay for the Quantitation of Human C4 Gene Products

Cited by 16 publications

References 18 publications

Diversity in Intrinsic Strengths of the Human Complement System: Serum C4 Protein Concentrations Correlate withC4Gene Size and Polygenic Variations, Hemolytic Activities, and Body Mass Index

Diversity in Intrinsic Strengths of the Human Complement System: Serum C4 Protein Concentrations Correlate withC4Gene Size and Polygenic Variations, Hemolytic Activities, and Body Mass Index

Quantitative and Antigenic Differences in Complement Component C4 between American Blacks and Whites

The Molecular Basis of Complete Complement C4A and C4B Deficiencies in a Systemic Lupus Erythematosus Patient with HomozygousC4AandC4BMutant Genes

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