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Biomedical subjects

E van Loghem

Publications and source records attributed to E van Loghem.

At least 55 records · Page 3Linked to original sources

A new case of gamma heavy chain disease: clinical, immunochemical and structural characterization.

A new case of gamma heavy chain disease (gamma HCD) is described in a 77-year-old woman. The serum and urine contain an M-component and electrophoretic, antigenic and ultracentrifugal properties resembling those of the Fc fragment of IgG globulin. Analysis on SDS-polyacrylamide gel electrophoresis and ultracentrifugal studies show that gamma HCD portein is present in the serum as a dimer with a molecular weight of 58,000 daltons. Analysis of isotypic and allotypic markers along with the structural studies show that this HCD protein belongs to the IgG subclass and that deletion includes the total VH and CH1 regions with sequence starting at residue 225 in the middle of the hinge region.

Aged↗

Production of antibodies to human immunoglobulins in a gibbon.

Immunization of a chimpanzee, a gibbon, a baboon and a rhesus monkey with human globulins gave different results. While chimpanzees did not produce any anti-human antibodies, baboon and rhesus monkey responded by producing anti-human IgG antibodies that did not show subclass or allotype specificity. In the gibbon antiserum, on the other hand, six different antibodies were demonstrated with a specificity against one or more of the four human IgG subclasses, including one allotype. Comparative investigations of non-human primate species sera showed that one of the specificities detected by these antibodies, i.e., the allotype G1m(f), was restricted to man; the other five antibodies reacted with man and with two or more genera of apes. Lower primates did not share any of these antigenic determinants. The extent of immunological distance is parallel to the taxonomic classification. The gibbon shows that there are more similarities between man and chimpanzee or pygmy chimpanzee than between man and gorilla or orangutan.

Animals↗

Immunoglobulin epitopes in primates.

Non-human primate sera were investigated for the presence of various human immunoglobulin epitopes including allotypes of kappa-, gamma 1-, gamma 2-, gamma 3- and alpha 2-chains, isotypes of kappa-, gamma 1-, gamma 2-, gamma 3-, gamma 4-, alpha 1-, alpha 2- and mu-chains and iso-allotypes. The non-human primate sera comprised representatives of several species of apes, Old World Monkeys, New World monkeys and prosimians. It is concluded that non-human primate immunoglobulins have many structural similarities with those of human IgM, IgA and IgG. The extent of these similarities parallels the taxonomic classification.

Alleles↗

A new case of gamma-3 heavy chain disease. Biochemical and immunological investigations.

A new gamma 3 heavy chain disease (gamma 3-HCD) protein (Emm) is described. A molecular weight of 70,000-80,000 daltons was estimated. Antigenic analysis showed that protein Emm lacks light chains and the CH1 domain of heavy chains, whereas the antigenic determinants of the gamma 3 Fc fragment (CH2 and CH3 domains) as well as those of the gamma 3 hinge region were present. Since the anomalous protein was temporarily present in serum Emm, a transient triggering of a cell clone which produces the gamma 3-HCD protein is suggested.

Chemical Phenomena↗

Anti-tissue antibodies and immunoglobulin levels in relation to HLA and other markers in Icelandic families.

Studies of 521 sera from the Icelandic cousin marriage project were made to assess the incidence of various anti-tissue antibodies and the levels of immunoglobulins, as these were considered to be useful markers of the humoral immune response. Comparisons were made between these parameters and the HLA-A and B antigens, the blood groups, the immunoglobulin allotypes (Gm, Km and Am), the properdin factor (Bf), and other markers. These investigations offered another approach to the study of the sites of action of immune response genes in man. Because the immune response may be expected to differ for each individual and depend at least in part, on the degree of exposure to different antigens, no absolute correlation was expected. There was, however, a marked association between certain IgG anti-tissue antibodies and HLA antigens. This was most marked for HLA-A10, B18 and b27, but not for HLA-A1 or B8. The comparison of immunoglobulin levels with HLA antigens, was less striking, although HLA-A2 appeared to be associated with low levels of IgE. There were also some associations between immunoglobulin levels and ABO blood groups.

Aged↗

Genetic control of survival in epidemics.

Descendants of Dutch colonists, who emigrated to Surinam in the last century and survived epidemics of typhoid and yellow fever with a total mortality of about 60%, were tested for twenty-six polymorphisms. The gene frequencies were compared with those of a large Dutch control sample. An analysis of drift indicated that the variations in gene frequencies observed for C3, Gm, HLA-B, and GLO were unlikely to be due to drift. Therefore these data might indicate selection through genetic control of survival in these epidemics.

Blood Group Antigens↗

Common and uncommon immunoglobulin haplotypes among Lebanese communities.

Allotypes of IgG1, IgG2, IgG3, and IgA2 subclasses were investigated in seven Lebanese communities (three Moslem and four Christian). The Gm-Am haplotypes found were mainly those prevalent in Caucasians with a low frequency of haplotypes usually observed in Africans and Orientals. The difference between highlanders and lowlanders as expressed by G2m(23) was highly significant and suggested a possible adaptation to selective pressure related to the gamma2 genes, possibly due to endemic malaria in the past. Exceptional Gm-Am haplotypes were unambiguously determined by family studies. Some were characterized either by a deletion or a repression or, in contrast, by a partial or total duplication of gamma genes. Two others had uncommon combinations of allotypes: Gm17;23;5,10,11,13,14 A2m1, where G1m (17) was present without G1m (1); and Gm3;23;5,14 A2m1, where the CH3 allotypes G3m (10,11,13) were lacking.

Gene Frequency↗

Antigenic analysis of the IgA component of LDH-IgA immunoglobulin complexes.

LDH-IgA complexes present in some human sera were purified by using affinity chromatography on 5'-AMP-Sepharose 4-B. The IgA component of the purified complexes was analysed in haemagglutination-inhibition tests. Antigenic determinants specific for alpha1 and alpha2 heavy chains and for kappa and lambda light chains were found. Earlier studies suggested that the IgA component is of kappa light chain type only. These different results are discussed. It is suggested that the LDH association site is located in the Fab fragment of the IgA component.

Epitopes↗

Immunoglobulin allotypes in African populations. I. Gm--Am haplotypes in a Nigerian population.

The study of immunoglobulin allotypes in various Negro populations has shown that their polymorphism is different from that in other populations. This particularly true for the alleles of the gamma3 and alpha2 locus. Numerous investigations have been made in which a limited number of markers were determined. It seems to be of importance to compare the results of the determination of all markers known at present in different tribes from various African countries. Such information may ultimately lead to additional support for theories on the origin and migration of early African inhabitants. In this paper we resent the results of the study of the first of a series of studies on African populations.

Black People↗

Serum genetic markers in a Newfoundland isolate with a familial aggregate of Hodgkin's disease.

Inherited genetic markers on the immunoglobulins and three other serum proteins were investigated in members of an isolated Newfoundland community. The frequencies found were compared with those from Europe. Whilst the incidence of the commonest variant forms were typically 'European', the occurrence of rare phenotypes pointed towards specific admixture from American Indians and Scandinavia. A possible contribution of these rare alleles, and of others, to pathogenesis in a familial aggregate of Hodgkin's disease within this community is discussed.

Gene Frequency↗

Localization of HLA on the short arm of chromosome 6.

A detailed marker gene study in a large Dutch kindred segregating for a reciprocal translocation between the chromosomes 6 and 20, t(6;20) (p21; p13), revealed a close linkage between the HLA genes and the breakpoint on the short arm of 6. During this study an apparent peak lod score of 2.9 was obtained at a recombination value of 0.05 for a linkage between HLA and the breakpoint, indicating that the chromosomal region, carrying the HLA genes, is situated near the breakpoint in band 6p21 close to the transition to 6p22.

Abnormalities, Multiple↗

Human IgG3 allotypes, with special reference to a new allotype related to G3m(g) (G3m21).

The IgG3 allotype described as L1 (Blanc et al., 1976) occurs on the CH3 region of G3m(g) proteins, in contrast to G3m(g) that is known to be present on the CH2 region. G3m(g) and L1 are, as a rule, present on the same gamma3 heavy chain, just like the G3m(b) subspecificities of the CH2 region, (b1) and (b4), with those of the CH3 region (b0), (b3) and (b5). Several families were investigated that showed inheritance of rare combinations of IgG3 allotypes. The data obtained are suggestive for notation of L1 as (g5), since L1 probably occupies a position antithetical to (b5). The relation of amino acid substitutions to allotypes and isoallotypes is discussed.

Alleles↗

Immunoglobulin haplotypes of two population groups in Iran.

Genetic markers of IgG and IgA were investigated in two population groups from Iran. The Gm-Am haplotypes found were mainly those prevalent in Caucasians, with a low frequency of Asiatic haplotypes. Twenty samples had phenotypes that led to the assumption of rare haplotypes. The main ones were: Gm(z;n;b)a2m(1) and Gm(za;n;g)A2m(2). The first haplotype differs from the common haplotypes because G1m(z) is present instead of G1m(f), and the second because it has G2m(n) and A2m(2) in combination with G1m(za) and G3m(g).

Alleles↗

Recombination, mutation, or constitutive expression at a Gm locus and familial hypergammaglobulinemia.

In a hypercholesterolemic Lebanese family, an uncommon Gm haplotype carrying an unexpected C gamma 1 gene was inherited by only one of 10 siblings. A new recombination during the maternal or paternal meiosis could explain its formation. According to this hypothesis, our data would be informative for the linkage relationship between the gamma-cistrons and the alpha 2-cistron. The latter might be located near the N-terminal side of the gamma-cistron linkage group, and the sequence of genes would be alpha 2, gamma 4, gamma 3, and gamma 1. A mutation could also effect the change from G1m(17) (codons AAA and AAG) TO G1m(3) (codons AGA and AGG). Another alternative is to postulate a constitutive expression of a C gamma 1 structural gene which, normally, would not be expressed. The uncommon derepression could be the consequence of uncommon cellular response to environmental, pathological or metabolic perturbation of a regulatory mechanism.

Adolescent↗

Immunoglobulin allotypes in Sardinia.

1218 individuals from Sardinia island (Italy) were tested for Gm and Km markers; 10 were not tested for Gm and only 401 were typed for Am markers. The peculiar genetic makeup of the Sardinian population is confirmed by their Gm allotypes. Their differences from those found in a control population of continental Italy (Ferrara), suggest ancient contacts with the Middle East and Africa. An indication for such contacts may also be found in the striking presence of the haplotype Gm f;n;bsc5, a haplotype not previously found in a human population. A significant difference of G2m(n) allotype was observed between highland and lowland regions. If confirmed, it may suggest an adaptive pressure related to the CH2 region of the gamma2 chain, possibly due to endemic malaria in the past.

Adolescent↗

Studies on fd fragments of human immunoglobulins. III. Immunogenic properties of gamma chains, myeloma fd gamma, and myeloma fd1 alpha.

Earlier studies on antisera against Fab of pooled human IgG and IgA myeloma proteins disclosed the presence of class-specific Fd antibodies, the demonstration of which required interaction of heavy and light chains. To extend our knowledge about the antigenic structure of the Fd fragment of human immunoglobulins, antisera were prepared in rabbits against gamma chains of pooled IgG and of four IgG1 myeloma proteins, and Fd gamma fragment and a cyanogen bromide-produced CH1 preparation of an IgG1 myeloma protein, and an Fd' alpha fragment of an IgA1 myeloma protein. No antigenic determinants exclusively confined to the CH1 region of intact human IgG could be demonstrated with these antisera. The antigenic structure of CH1 intact immunoglobulins may thus only be defined by light-chain-dependent determinants.

Amino Acids↗

Quantification of IgG subclasses in sera of normal adults and healthy children between 4 and 12 years of age.

The concentration of the four subclasses of IgG was determined in sera of normal adults and healthy children between 4 and 12 years of age, using the radial immunodiffusion technique. A relation between the concentration of IgG subclasses and Gm type was studied in adults. No influence of Gm type on IgG1 concentration could be shown, except that the group of Gm(fb) individuals had a higher level than the others. The mean concentration of IgG2 was higher in sera positive for Gm(n) than in those lacking this genetic marker. High IgG3 concentrations corresponded to the presence of Gm(b). No clearcut evidence was obtained for a relation between IgG4 concentration and Gm factors, although in general Gm(n) positive individuals had higher and Gm (zag) positive individuals lower concentrations of this subclass in their serum. Quantification of IgG subclasses in sera from healthy children of different ages revealed that the amount of IgG2 rises slowly with age, having not yet reached the adult level at the age of 12 years. This also holds for IgG4, although in a lesser degree. No significant differences from the adult level were found for the concentrations of IgG1 and IgG3.

Adult↗