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C M Giles

Publications and source records attributed to C M Giles.

At least 37 records · Page 2Linked to original sources
PubMed1988

Antigenic determinants of human C4, Rodgers and Chido.

The duplicated genes, C4A and C4B, are located within the major histocompatibility complex on chromosome 6 and each exhibits a high degree of polymorphism expressed as both electrophoretic and antigenic variation (Rg/Ch). Eight high-frequency antigens and one low-frequency antigen have been defined by immune human polyspecific antisera in haemagglutination inhibition assays. Close association exists between different C4 allotypes and the antigens they express. Normally, C4A expresses Rg and C4B has Ch but rare reverse associations exist. Nucleotide sequences of the C4d region from C4 allotypes of known antigenic status have demonstrated four polymorphic sites that correlate with the antigens, which, in a structural model, are seen to be conformational or sequential epitopes. The observed interrelationships of the antigens on C4 allotypes accommodated by the model suggest that the electrophoretic variation is located outside the C4d region. The molecular genetics of C4 are also considered as part of the polymorphism.

Amino Acid Sequence↗
PubMed1987

The study of a French family with two duplicated C4A haplotypes.

The finding of two duplicated C4A haplotypes in a normal French family led to a detailed study of their C4 polymorphism. The father had an extremely rare A*6A*11, B*QO haplotype inherited by all of his children and the mother had the more common A*3A*2, B*QO haplotype. Two HLA identical daughters only have four C4A alleles. The father's A11 allotype expresses Ch:1 (Chido) rather than Rg:1 (Rodgers) and represents a new Ch phenotype Ch:1,-2,-3,-4,-5,-6. In order to clarify the genetic background in this unusual family, DNA studies of restriction fragment length polymorphisms (RFLPs) were undertaken. The father's rare haplotype, which expresses two C4A allotypes, results from a long and a short C4 gene normally associated with the A*6, B*1 that also exhibits the Bg/II RFLP. As it travels in an extended MHC haplotype HLA A2, B57(17), C2*C, BF*S, DR7 that is most frequently associated with A*6, B*1, we postulate that the short C4B has been converted in the alpha chain region to a C4A gene which produces a C4A protein. This report of a short C4A gene is the first example in the complex polymorphism of C4.

Alleles↗
PubMed1987

There are two C4 genetic loci and a null allele in the chimpanzee.

Genetic polymorphism in C4 in the chimpanzee was studied by agarose gel electrophoresis of desialated plasma and development of patterns by immunofixation with antiserum to human C4 and by a C4-sensitive hemolytic overlay. In general, immunofixation patterns showed multiple partially overlapping bands of which only the most cathodal had strong hemolytic activity. In analogy to human C4, the latter were designated C4B, whereas those detected by immunofixation which had little hemolytic activity were designated C4A. Chimp C4A and C4B reacted with human and mouse (monoclonal) anti-C4B and human anti-Ch1 but neither reacted with monoclonal anti-C4A or human anti-Ch2, Ch3, Rg1, or Rg2. On sodium dodecyl sulfate polyacrylamide gel electrophoresis, the alpha chain of C4B showed a slightly lower apparent relative mass than that of C4A at around Mr 93,000. There were three C4A variants and two C4B variants inherited in families as autosomal codominant traits, as C4A-C4B cosegregating pairs with no detectable crossing-over. These pairs were inherited with chimpanzee leukocyte antigen types C2 and BF variants without detectable crossing-over. Half-null C4 haplotypes with C4B QO were observed in family studies. Nine BF, C2, C4A, C4B allelic haplotypic combinations (complotypes) were identified among presumably unrelated chimpanzees.

Alleles↗
PubMed1987

Three Chido determinants detected on the B5Rg+ allotype of human C4: their expression in Ch-typed donors and families.

A study was made of polyspecific human allo-anti-C4, anti-Chido (Ch), which reacts with determinants usually located on C4B protein. Some anti-Ch reagents are capable of reacting with Ch- red cells coated with C4 from Ch:-1,-2,-3 donors. A complex serologic pattern demonstrated three more Ch determinants, Ch4, Ch5, and Ch6, which were detected by haemagglutination-inhibition tests. All Ch:1,2,3 samples were Ch:4,5,6 but samples lacking one or more of the Ch1,Ch2,Ch3 series of determinants also lacked some of the new determinants. MHC typed families demonstrated the inheritance of the new determinants as part of the Ch haplotype, and associations with C4 allotypes and haplotypes have been established. Ch4 always associates with C4B protein. Ch5 and Ch6, normally detected on C4B protein, were detected in several individuals who lacked C4B (BQO allotypes) and were therefore presumed in these instances to be located on the accompanying C4A protein.

Antigens, Surface↗
PubMed1987

Allo-anti-Chido in a Ch-positive patient.

Allo-anti-Chido (Ch) was detected in a patient whose red cells typed as Ch+. The C4 allotype of the patient was A4,B2 which associates strongly with the Ch phenotype Ch:1,-2,3,4,-5,6. Anti-Ch2 + Ch5 were the Ch specificities identified. Absence of only Ch2 and Ch5 determinants on the C4B protein allowed this unique immune response to blood transfusion.

Aged↗
PubMed1987

Expression of MHC class I determinants on erythrocytes of SLE patients.

Strong expression of MHC Class I determinants had been observed on the erythrocytes of three genetically C4 deficient patients who all had SLE. In a study of 35 other SLE patients who were not C4 deficient, 30 showed a marked increase in the expression of MHC Class I on their erythrocytes. There was a correlation between the expression of erythrocyte Class I and disease activity. The polymorphic HLA determinants were detected by haemagglutination with human cytotoxic antisera from untransfused pregnant women. A shared monomorphic epitope of HLA-A, -B and -C, and beta 2-microglobulin were detected by haemagglutination with monoclonal antibodies. A monoclonal antibody for a monomorphic epitope on MHC Class II alpha and beta chains did not react. Erythrocytes from a group of RA patients and a group of normal controls had moderate and low expression respectively. We suggest that MHC Class I may be induced on erythrocytes maturing in a milieu containing mediators derived from activated cells of the immune system. Aberrant tissue expression of MHC antigens may be more widespread than has been previously recognized in diseases mediated by immune mechanisms.

Arthritis, Rheumatoid↗
PubMed1986

Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity.

The human complement components C4A and C4B are highly homologous proteins, but they show markedly different, class-specific, chemical reactivities. They also differ serologically in that C4A generally expresses the Rodgers (Rg) blood group antigens while C4B generally expresses the Chido (Ch) blood group antigens. C4A 1 and C4B 5 are exceptional variants which possess their class-specific chemical reactivities, but express essentially the reversed antigenicities. The genes encoding the typical Rg-positive C4A 3a and Ch-positive C4B 3 allotypes and the interesting variants C4A 1 and C4B 5 have been cloned. Characterization of the cloned DNA has revealed that the genes encoding the A 3a, A 1 and B 3 allotypes are 22 kb long, but that encoding B 5 is only 16 kb long. Comparison of derived amino acid sequences of the polymorphic C4d fragment has shown that C4A and C4B can be defined by only four isotypic amino acid differences at position 1101-1106. Over this region C4A has the sequence PCPVLD while C4B has the sequence LSPVIH, and this presumably is the cause of their different chemical reactivities. Moreover, the probable locations of the two Rg and the six Ch antigenic determinants have been deduced. Our structural data on the C4A and C4B polymorphism pattern suggests a gene conversion-like mechanism is operating in mixing the generally discrete serological phenotypes between C4A and C4B.

Amino Acid Sequence↗
PubMed1986

HLA haplotypes with C4B5; evidence for further allelic heterogeneity.

Twenty-three individuals from various disease groups and normal controls were identified by immunofixation with anti-C4, C4-dependent lysis, determination of Rg (Rodgers) and Ch (Chido) phenotypes, and immunoblotting with C4-specific mouse monoclonal antibody. We found that one haplotype predominates with the C4B*5 allele, HLA-A11, B22(55), Cw3, Bf*S, C4A*4B*5, which also carries the Ch1,-2, 3 haplotype. The B5 allotype was also found with HLA-B60, HLA-B35 in Caucasoids, and HLA-B18 in non-Caucasoids; these carried the Ch-1, -2, -3 haplotype. Our results are in accord with an earlier report of two B5 subtypes, B5Rg+ and B5Rg- (Roos et al. 1984). The specificity of the mouse monoclonal antibodies IC4 and 2B12 had been previously related to C4A and C4B, respectively, but our results suggest that they relate more closely to Rg and Ch determinants.

Alleles↗
PubMed1985

C4B3 allotype with a novel Ch phenotype.

The fourth component of complement (C4) has two classes of protein, C4A and C4B, both of which have many allelic forms. The serological determinants Rodgers (Rg1, Rg2) and Chido (Ch1, Ch2, Ch3) are generally associated with C4A and C4B, respectively. The C4B3 allotype has been detected in a single Canadian family that expresses a novel Ch phenotype, Ch:-1, 2, -3. There was no information for the Rg determinants, as the C4A*2B*3 haplotype would normally express Rg on the C4A protein. Other C4B3 allotypes in informative families have different Ch phenotypes, and the relationships of these within extended major histocompatibility complex haplotypes are discussed in this paper.

Alleles↗
PubMed1985

'Partial inhibition' of anti-Rg and anti-Ch reagents. I. Assessment for Rg/Ch typing by inhibition.

Many examples of anti-Rg (Rodgers) and anti-Ch (Chido) have been studied by titration-inhibition to assess their ability to detect partial inhibition (p.i.). Generally, anti-Rg distinguishes the inhibition type Rg+ from Rg(+) (p.i.) and Rg-, whereas anti-Ch distinguishes Ch- from Ch+ and Ch(+) (p.i.). Serological procedures for the detection of p.i. in random samples and the results of typing one family, apparently giving anomalous results, are discussed.

Blood Group Antigens↗
PubMed1985

'Partial inhibition' of anti-Rg and anti-Ch reagents. II. Demonstration of separable antibodies for different determinants.

Partial inhibition (p.i.) of anti-Rg (Rodgers) and anti-Ch (Chido) has been detected by antisera considered to be polyspecific. By using cells and C4 from individuals that are p.i. of Rg and Ch in absorption and elution experiments with selected antisera, it has been possible to separate several specificities. 2 Rg determinants, Rg1 and Rg2, and 3 Ch determinants, Ch1, Ch2, and Ch3, are defined by specific antisera. Partial inhibitors for Rg lack Rg2 and for Ch lack Ch2 or Ch3. The results are discussed in relation to other complexities of C4 polymorphism.

Antibody Specificity↗
PubMed1984

Human C4 polymorphism: pedigree analysis of qualitative, quantitative, and functional parameters as a basis for phenotype interpretations.

Ten families with 82 members were investigated for C4A- and B polymorphism in a blind trial. Phenotyping was done on neuraminidase treated sera by immunofixation and simultaneously by hemolytic overlay electrophoresis. In addition Rg, Ch, BF, C2, HLA-A, B, C, DR, and GLO were determined. After decoding the samples the reliability of blind typing was found to be 84.4% according to segregation patterns. Inconsistencies occurred mostly when A4, A2, or A92 were present. The detection of silent A*Q0 and B*Q0 alleles was more critical than that of "difficult" allotypes. The quantitation of the C4A/B ratio by densitometry of stained gels or by conventional immunochemical measurements of serum C4 level could not substantially improve the identification of A*Q0 or B*Q0. C4 dependent activity in radial diffusion hemolysis showed satisfactory correspondence with the number of expressed C4B alleles. At least three haplotypes with two C4A genes (duplicated A genes) were observed as ascertained from offspring analysis in accordance with the MHC segregation pattern. Individuals with the duplicated C4A gene (C4A*3, A*2, in the absence of any other expressed A allele or together with C4A*92) showed only partial inhibition of Rodgers antisera. Partial inhibition of Chido antisera was seen in individuals with C4B 2 (in the absence of other B allotypes). The findings support the hypothesis of at least two structural C4 loci. They also demonstrate the inconsistency of quantitative data in the recognition of silent alleles.

Alleles↗
PubMed1984

Genetics of human C4 polymorphism: detection and segregation of rare and duplicated haplotypes.

Applying a combined technology for the detection of allotypic variation of the fourth component of human complement (C4), including immunofixation with anti-C4 and C4-dependent lysis after agarose electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of C4 to separate the C4A and B alpha-chains, and the determination of Rodgers (Rg) and Chido (Ch) determinants of C4 in serum and at the blotted C4 alpha-chains, we detected rare human C4 allotypes and studied the genetic linkage. Partial inhibitors (p.i.) of anti-Rg and anti-Ch sera were found; the C4A51 allotype characterized as Rg p.i. and the C4A1 and C4B51 allotypes as Ch p.i. were genetically inherited. The C4A1 allotype has a unique Rg- Ch+ C4A alpha-chain. Duplicated C4A loci, A*3, A*2, and A*5, A*2 were both associated with a C4BQO and the HLA haplotype A3-Cw4-Bw35-DR1. These additions to the already known extensive C4 polymorphism may help to sort out their significance for the biological functions of human C4.

Complement C4↗
PubMed1984

Partial C4 deficiency in subacute sclerosing panencephalitis.

In an immunogenetic study, 23 subacute sclerosing panencephalitis (SSPE) patients and their families were studied for the HLA region markers HLA-A, B, C, DR, BF, C2, C4A, C4B, GLO I, and PGM3. In addition, C3, C4, and factor B serum levels were determined. A highly significant association of C4A QO with SSPE was found. Furthermore, two rare haplotypes, C4A QOB QO, two C4ACh+ allotypes, and four Ch partial inhibitors were detected, which possibly impair the function of the C4 molecules. HLA-DR5 was increased. In addition, a number of rare HLA-A, C, B, DR haplotypes were observed. It is postulated that rare C4 molecular deficiency might be a predisposing factor in the pathogenesis of SSPE.

Complement C4↗
PubMed1984

A new genetic variant for Chido.

A new and distinct partial inhibition pattern was observed for Chido during routine typing; it is found in 3% of random samples, shows recessive inheritance and is linked to HLA. Polyspecificity in anti-Ch reagents, selected to detect partial inhibition, is demonstrated.

Binding Sites, Antibody↗