Human C4 polymorphism: Pedigree analysis of qualitative, quantiative, and functional parameters as a basis for phenotype interpretations

Mauff, G.; Bender, Klaus; Giles, Carolyn M.; Goldmann, S. F.; Opferkuch, W.; Wachauf, Barbara

doi:10.1007/bf00291561

Cited by 42 publications

(25 citation statements)

References 37 publications

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“…From RM measurements the alleles were diagnosed as C4A '92', C4A 12 and the common C4A 3. A '92' was distinct in RM values from A 91 and therefore tentatively introduced pending future side-by-side comparison with a C4A 92 variant described earlier [36] but never defined in a reference exercise. A 4th band migrating in the position of C4A 2 was considered to be the minor band of A '92' since only 3 alleles appear to be expressed from C4·-chains and TaqI RFLP.…”

Section: Resultsmentioning

confidence: 99%

Reference Typing Report for Complement Component C4

Mauff¹,

Luther²,

Schneider

et al. 1998

Exp Clin Immunogenet

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During the 7th Complement Genetics Workshop, Mainz, Germany, May 1998, a complement component C4 typing exercise took place with the aim of applying present technologies to the definition of reference C4 alleles/phenotypes and the recognition of nonexpressed (Q0) C4 alleles within expressed haplotypes. Eleven samples were submitted from 3 laboratories and tested by 14 participating laboratories with basic protein-typing technologies; in addition, each laboratory contributed data from local expertise. The samples were introduced to the reference typing for one or more characteristic allotype or for partial or total nonexpression of one isotype. The blinded samples were centrally evaluated and the results discussed among the participants at a plenum meeting. From the results, the samples could be classified into a group of common, easy to diagnose pheno-/allotypes, less common but still unanimously recognised variants, and a third group with difficult pheno-/allotypes. Within the latter group, the allotypes were either new (C4A ‘92’; C4B ‘93’) and/or showed partial or total reversed antigenicity and unusual Rodgers/Chido (Rg/Ch) PCR subtypes (C4A ‘92’; C4A 12; C4B ‘35’; C4B ‘13’). Semiquantitative C4-α-chain estimates of relative isotype levels correlated well with the number of alleles seen at each locus by agarose gel electrophoresis, and were superior to other isotype quantitation methods. From the evaluation of the reference typing it was concluded that the recognition of rare, aberrant or hybrid C4 alleles with partial or total reversed Rg/Ch antigenicity or monoclonal reactivity is still difficult in most instances; besides isotype-dependent lysis, relative migration values, immunoblots with Rg- and Ch-specific monoclonal antibodies, Rg/Ch PCR typing, side-by-side comparison with already described allotypes will ultimately be required. The recognition of nonexpressed alleles within C4A and C4B expressed phenotypes remains the major obstacle in C4 genetic typing. Finally, a conclusive interpretation of DNA typing results will be achieved only in the context of complete allotyping results at the protein level, and at present cannot replace conventional protein allotyping.

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Section: Resultsmentioning

confidence: 99%

Reference Typing Report for Complement Component C4

Mauff¹,

Luther²,

Schneider

et al. 1998

Exp Clin Immunogenet

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“…crossed immunoelectrophoresis gels [13]. While scanning densitometry is more precise than visual interpretation, it has not substan tially improved the detection of C4 null al leles [23]. It may be difficult to determine heterozygous C4 nulls in samples exhibiting overlapping electrophoretic bands.…”

Section: Discussionmentioning

confidence: 99%

“…The rare exception would be the C4A1 allotpye which is Rgl negative and Chi positive and some C4B5 allotypes that are Chi negative. The frequencies of C4A1 and C4B5 are each less than 1 % and thus this should not pose a significant problem for quantitation in a Cau casian population [22], Traditional methods for the detection of relative amounts of C4A and C4B proteins have been visual inspection or densitométrie scanning of C4-allotyping gels [8][9][10][11]23] or…”

Section: Monoclonalsmentioning

confidence: 99%

A Novel Immunoassay for the Quantitation of Human C4 Gene Products

et al. 1990

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Utilizing mouse monoclonal antibodies which recognize Rodgers 1 and Chido 1 epitopes carried on the C4A and C4B molecules, and heat-aggregated IgG to activate Cl, an immunoassay was developed for the quantitation of total C4 as well as C4A and C4B. Interassay variation was 12.4, 11.5 and 10.8%, respectively. The immunoassay was compared to the quantitation of total C4 by radial immunodiffusion by testing 103 random white controls and gave a Pearson’s product-moment correlation coefficient of 0.81. Three genetic total-C4-deficient individuals were nonreactive in all three assays. This activated assay is specific, reproducible, and superior to existing methods for the quantitation of C4A and C4B and detection of the heterozygous C4 null state.

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“…C4A and C4B can be distinguished by specific antisera, anti-Rogers and anti-Chido respectively, and reversed correlation have been found infrequently (Giles, 1990). Mauff et al (1984) showed that the C4B protein has a higher hemolytic activity than C4A. These functional and structural differences have been determined by a sequence of four amino acids in the C4d region (Yu et al, 1988).…”

Section: Introductionmentioning

confidence: 99%