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Biomedical subjects

E van Loghem

Publications and source records attributed to E van Loghem.

At least 19 recordsLinked to original sources
PubMed1987

Lymphoid chimerism after allogeneic bone marrow transplantation. Y-chromatin staining of peripheral T and B lymphocytes and allotyping of serum immunoglobulins.

Lymphoid cell engraftment was monitored for several years after bone marrow transplantation by Y-chromatin staining of T and B lymphocytes in the peripheral blood and/or by immunoglobulin allotyping in the serum of 20 of 52 pediatric patients grafted successively between October 1973 and October 1983. Data on 2 patients with severe combined immunodeficiency, grafted earlier in December 1968 and April 1971, are also included. These children received an allogeneic bone marrow graft for leukemia (n = 7), severe aplastic anemia (n = 11), or severe combined immunodeficiency (n = 4) and were informative for this study, because they differed from their donor by sex (n = 16) and/or by immunoglobulin phenotype (n = 13). Of 16 pairs in which the donor was of the opposite sex, 11 patients ultimately showed circulating T and B lymphocytes of donor origin after bone marrow transplantation; in the remaining 5, there was an incomplete chimerism of the circulating lymphoid cells. Of 13 pairs with a difference in immunoglobulin phenotype between donor and recipient, 8 patients exhibited donor allotypes 3 months or later after transplantation, in 3 of them together with recipient allotypes. In the remaining 5 patients, recipient allotypes were detected after transplantation, but the simultaneous presence of donor-type immunoglobulin production could not be excluded in 4. The persistence of either a split (T lineage of donor origin and B lineage of recipient origin) or mixed (T and/or B lineage of donor and recipient origin) chimerism was related to the type of disease. In 3 children circulating B cells of donor-origin did not fit with the recipient origin of the sessile immunoglobulin-secreting plasma cells. This implies that different immune compartments--e.g., bone marrow and peripheral lymphoid tissues--should be investigated following allogeneic bone marrow transplantation. A prolonged presence of recipient-type lymphoid cells increased the risk of leukemic relapse in the patients investigated.

Adolescent↗
PubMed1986

Gene conversion in human immunoglobulin gamma locus shown by unusual location of IgG allotypes.

The constant region of the gamma 1, gamma 2 and gamma 3 heavy chains of the human IgG1, IgG2 and IgG3 immunoglobulins carries antigenic determinants or G1m, G2m and G3m allotypes, which are genetic markers of these subclasses. The exceptional presence on gamma 1 and gamma 2 chains of Gm allotypes usually located on the CH3 domain of gamma 3 shows an unexpected clustering of base changes and subsequent identity of short DNA sequences in the CH3 exon of the non-allelic gamma 1, gamma 2 and gamma 3 genes. Such clusters of substitutions are not easily explained on the classical basis of point mutations. A gene conversion, which substituted a segment of the gamma 1 or gamma 2 gene with the homologous region of the non-allelic gamma 3 gene, is more likely. Other examples of possible conversion involving the gamma genes are described. The conservation or the restoration of short sequences produced by the conversion events might be related to the biological properties of the constant region of the heavy chains.

Alleles↗
PubMed1986

Molecular analysis of a case of IgA2 deficiency.

A family with two members with selective IgA2 deficiency was analysed by direct gene analysis with different probes for the IgCH region. No gross gene deletions or rearrangements were detected. Genetic analysis based on serological and molecular markers did not rule out linkage with the IgCH region. However, a defect of other genes not linked to the Ig heavy chain region and controlling the expression of IgA may be possible as well.

Dysgammaglobulinemia↗
PubMed1986

Allotypic markers.

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Amino Acid Sequence↗
PubMed1985

Immunoglobulin allotypes in Hungarian Gypsies. Relationship to populations from India.

The allotypic markers of immunoglobulin heavy chains (Gm, Am and Em allotypes) provide important contributions to the differentiation between populations, and they are informative for tracing racial origin, migration and admixture of isolates and stray groups. The combined G1m; G2m; G3m; A2m; Em haplotypes are a highly polymorphic system that is a powerful tool in population genetics because of the existence of haplotypes that are unique for a particular race. In this paper, data on Gypsies living in Hungary are compared with those obtained in other populations, in particular Hindus and non-Hindus from India. The analysis agrees with anthropological and philological evidence for population movements from Asia to Europe.

Ethnicity↗
PubMed1985

Correlation between G2m(n) immunoglobulin allotype and human antibody response and susceptibility to polysaccharide encapsulated bacteria.

To determine whether genetic factors influence the human antibody response to polysaccharides, we correlated Ig allotypes with the concentrations of antibody to 14 bacterial capsular antigens in 130 actively immunized Caucasian adults. The 88 individuals possessing G2m(n), an allotype antigen of IgG2 subclass heavy chains, had significantly higher postimmunization antibody levels to Haemophilus influenzae type b (Hib) and 8 of 11 pneumococcal types (P less than 0.05) than the 42 lacking this antigen. For Hib, pneumococcus type 14, and meningococcus group C, an increased response was observed in IgG class but not in IgM or IgA classes of antibody. The G2m(n) positive individuals also had higher preimmunization antibody levels to most polysaccharide antigens. Total IgG2 concentrations were correlated with the mean postimmunization antibody concentrations to pneumococci (P = 0.005), but this correlation was independent of G2m(n) by multiple regression analysis. To determine if the lack of G2m(n) was associated with increased susceptibility to infection, we compared the frequencies of various Ig allotypes in 98 children infected with Hib and 98 matched controls. Caucasian children with Hib infections other than epiglottitis were significantly more likely to lack the G2m(n) allotype than controls (P less than 0.05). G2m(n) negative Caucasian children less than or equal to 18 mo old have a 5.1-fold higher risk of nonepiglottitic Hib infections than G2m(n) positive children (P less than 0.01). We conclude that allotypic variants of the gamma-2 heavy chain genes, or genes in linkage equilibrium with them, exert a regulatory influence on the caucasian antibody response to a variety of immunologically distinct bacterial polysaccharide antigens. Young Caucasian children of the low responder phenotype, i.e., those lacking the G2m(n) allotype, are genetically predisposed to Hib and perhaps other bacterial infections.

Adult↗
PubMed1984

Immunoglobulin heavy chain haplotypes in caucasian New Zealanders.

In the course of studies on the genetic basis of autoimmune disease, immunoglobulin allotypes were measured in New Zealand people of caucasian origin. We report the observed frequencies of the various allotypes of the gamma heavy chains, together with the frequencies of the combinations observed to occur in individuals (phenotypes) and the nature and frequency of the combinations on individual chromosomes (haplotypes), as calculated by application of Kurczynski and Steinberg's computer programme MAXIM.

Female↗
PubMed1984

A solution to the genetic and environmental puzzles of insulin-dependent diabetes mellitus.

Studies of the segregation of heterozygous immunoglobulin allotypes in families with several cases of insulin-dependent diabetes mellitus (IDDM) show that germline heavy-chain V (variable region) genes are not major genetic determinants for IDDM, but data for IDDM and Graves' disease together suggest involvement of kappa light-chain V genes. Absence of IDDM at birth, the semi-random age of onset, and the 50% discordance of identical twins suggest that somatic mutation of germline V genes is involved in the development of the pathogenetic anti-beta-cell clones. The effect of histocompatibility and other alloantigens on the prevalence of IDDM is readily accounted for by the effect of the "holes" they induce, by natural tolerance, in the immune response repertoire; these alterations apparently affect the chance of emergence of anti-beta-cell clones by the somatic mutations and network of interclonal deletions that constantly change the fringes of the repertoire. Histocompatibility antigens can also influence repertoire development by changing the specificity of conjoint presentation of foreign antigens by macrophages. Antigenic stimulation by particular environmental microorganisms is probably essential to the repertoire development necessary for the occurrence of IDDM. Additionally, beta-cell damage by local infection may play a part by facilitating autoantigen presentation to the immune system.

Antigens, Viral↗
PubMed1984

Genetic linkage between erythrokeratodermia variabilis and Rh locus.

A genetic linkage study was performed in a large Dutch kindred with erythrokeratodermia variabilis (EKV, McKusick no. 13320). The autosomal-dominant trait appeared to segregate rather consistently with the cde (r) gene complex of the Rh system. Only one recombinant was found amongst 27 informative individuals. Lod score calculations gave strong evidence for close linkage between the loci for EKV and Rh (with a maximum lod score of 5.55 at a recombination fraction of 0.044).

Chromosomes, Human, 1-3↗
PubMed1984

HLA and GM in insulin-dependent diabetes in the Netherlands: report on a combined multiplex family and population study.

This report deals with the genetic factors involved in insulin-dependent diabetes mellitus (IDD) in The Netherlands. Twenty-two Dutch multiplex families with IDD were typed for HLA-A, -B, -C, and -DR antigens, for BF, C2, C4, and GLO polymorphisms, as well as for GM allotypes of immunoglobulins. In addition, 53 unrelated IDD children and 31 unrelated patients with adult onset IDD were typed for HLA-A, -B, -C, and -DR antigens. A significant heterogeneity for the frequency of HLA-DR4 related to age of onset was observed. A significant deviation of the Hardy-Weinberg equilibrium was observed for the HLA-DR locus with an excess in patients of heterozygotes HLA-DR3, -DR4.HLA-B8, and HLA-B15 were not only secondary associated, but constituted with HLA-DR3 and -DR4, respectively, a haplotype in association with IDD. Nonrandom segregation of HLA-haplotypes was observed in multiplex families exemplified by an excess of HLA-identical affected sibpairs . Cross- overs between HLA-DR and GLO identified the HLA-DR segment as mainly involved in the association with IDD. Three diabetic haplotypes were confirmed to occur frequently among affected sibs: (a) A1, B8, BFS, C2.1, C4AQO , C4B1 ,DR3, GLO2 ; (b) Aw30, Cw5 ,B18,BFF1,C2.1, C4A3 , C4BQO ,DR3, GLO2 ; (c) A2,Cw3, B15,BFS, C2.1, C4A3 , C4B3 , DR4,GLO1. The segregation of GM allotypes to affected sibpairs was not significantly different from random segregation. The main conclusions from this study are that significant heterogeneity for age of onset exists and that the data are not compatible with simple genetic models including dominant, recessive, and intermediate models of inheritance. The data do require more complex models, involving two different HLA-linked (sets of) susceptibility genes.

Adolescent↗
PubMed1984

A genetic marker of human IgE heavy chains, Em(1).

A monoclonal anti-IgE antibody was obtained that reacted with some IgE myeloma proteins and with all but a few normal sera. Family studies proved that a genetic marker of IgE had been detected. This allotype, called Em(1), segregates in association with certain Gm-Am haplotypes. The available quantitative evidence warrants the conclusion that human IgE has genetic variants, but no subclasses. Samples from various populations of five continents, representative for the respective prevalent Gm-Am haplotypes, were tested for Em(1). Em(1) was absent mainly in haplotypes carrying A2m(2) and G2m(n). These closely linked genes are located in a chromosomal region that comprises the gamma 2-gamma 4-epsilon-alpha 2 CH genes. A hypothesis for the generation of Em(1) is given.

Africa↗
PubMed1984

Monoclonal antibodies to an immunoglobulin allotype marker G1m(f).

The properties of a group of mouse monoclonal antibodies (McAbs) specific for the human G1m(f) allotype marker on immunoglobulin G are described. The specificity of all 5 McAbs was anti-Gm(f) in haemagglutination assays detecting the G1m(f) determinant on 6 ng of purified G1m(f) paraproteins. A high dilution (greater than or equal to 1/10(4)) could be used for the majority of McAbs in this assay. In Elisa the G1m(f) marker could be detected in homozygote G1m(f+z-) sera at a serum dilution of greater than or equal to 1/10(4). In Elisa assays the G1m(f) specificity was lost when IgG was bound directly to polystyrene but was restored when IgG was bound via anti-human IgG to the polystyrene plate. A possible conformational change in IgG to account for this loss of specificity is discussed. It is expected that these McAbs with their high titre and increased sensitivity over conventional Gm antisera will allow more detailed analysis of the Gm marker system.

Animals↗
PubMed1984

Genetic study of Tunisian Berbers. I. Gm, Am and Km immunoglobulin allotypes and ABO blood groups.

The Gm, Am and Km immunoglobulin allotypes and ABO blood groups were studied in three groups of Tunisian Berbers . The results showed that the actual Berbers of Tunisia present certain heterogeneity and their ancestors were probably the first inhabitants of North Africa. Indeed, although their Gm-Am haplotypes are mainly Caucasoid, some of them are typically African. The group of Kesra village, the most Caucasoid, shows frequencies of Gm-Am haplotypes very close to those of South European populations, particularly the Spanish, who are probably of the same origin. The gene frequencies of the ABO groups in the three Berber groups were similar to those recorded in European populations with a relatively high frequency of the O genes typical of the Berbers .

ABO Blood-Group System↗
PubMed1983

Allotypic and isotypic aspects of human immunoglobulin A.

The location of isotypic, isoallotypic and allotypic determinants is reviewed in the light of data obtained when specific antisera are tested with proteolytic fragments of IgA molecules or mutants of IgA obtained from patients with alpha-heavy chain disease. Isotypic determinants are distributed throughout the alpha chain constant regions although when intact IgA proteins are used as immunogens the CH3 domain is immunodominant. Alpha 1 subclass specific isotypic determinants are present in both Fab and Fc fragments. Amino acid sequence analysis suggest that alpha 1 subclass isotypic determinants depend on substitution in the CH1, hinge and/or CH2 domain. The isoallotypic determinants nA2m(2) appears to be located on the CH1 domain and appears to require disulphide-linked alpha chains for its expression. The allotypic determinant A2m(2) appears to be located in the CH3 domain involving residues 428, 458 and/or 467. The latter residues are present in both A2m(1) and A1 proteins which indicates that for A2m(1) to be the antithetical determinant of A2m(2), the determinant formed by residues 428, 458 and/or 467 in these proteins must be influenced by subclass differences which allows its expression in A2m(1) proteins and not in A1 proteins.

Amino Acid Sequence↗
PubMed1983

Gm markers in celiac disease.

The association of Ig allotypes with celiac disease was analyzed in a sample of 95 Italian patients typed for HLA polymorphisms. No significant association was found for any Gm, A2m, or Km specificity when the overall sample was considered. However, significant different sex ratios were shown by patients' fnb positive and fnb negative genotypes, with a relative risk of 10.7 for this haplotype in males, suggesting that sex and Gm influence the penetrance of the HLA-linked genes. The significance of this finding is strengthened by the recent report that H-2 and Ig allotypes intervene in the genetic control of murine immune response to A-gliadin (M.F. Kagnoff, Nature 296:158, 1982).

Adult↗
PubMed1983

Distribution of antigenic determinants on human IgA1.

The distribution of antigenic determinants on human IgA was studied with fragments and mutants of IgA1. F(abc)2 and Fabc, lacking the CH3 domain, F(ab')2 and Fab', lacking the CH2 and CH3 domain, Fab that further lacks most of the hinge region, and Fc fragments were included in our investigations. Antibodies specific for the CH3 domain of IgA1 were found in antisera raised against an alpha 1-HCD protein and in anti-Fc alpha antisera. The antisera detected different antigenic determinants on CH3 as was shown by inhibition with sera from nonhuman primates. An anti-Fc5 mu antiserum detected a determinant on Fc common to IgA and IgM. The serum of an IgA-deficient individual reacted with a determinant on CH2 of four-chain molecules only. A subclass-specific anti-Fabc antiserum detected a determinant which needed interaction of CH2 and CH1 or the hinge region. Anti-Fab antisera reacted with class or subclass specific determinants on CH1. The isoallotype nA2m(2) is probably located on CH1. Its expression requires two alpha-chains stabilized in a conformation attributed to by CH2.

Animals↗