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G de Lange

Publications and source records attributed to G de Lange.

At least 19 recordsLinked to original sources
PubMed1998

Molecular characterization of immunoglobulin G4 gene isoallotypes.

The molecular bases of classical serological immunoglobulin allotypes are progressively uncovered through detailed characterization of the relevant genes. Here we describe two isoallotypic determinants of the G4 gene. In the first, Leu 309, as in G1 and G3, is changed to Val, as in G2; studies on myeloma proteins have long assigned the immunologically defined nG4 m(a)/(b) to the same position. The two molecular variants, here called IGHG4*L309 and IGHG4*V309, are allelic in IGHC haplotypes with a single G4 gene, but can be found together in cis in G4-duplicated haplotypes. A second isoallotypic variant was found at codon 409, where either Arg, as in G1 and G3, or Lys, as in G2, can be found. Both isoallotypes are associated with several 'silent isoallotypic' substitutions dispersed through the hinge, CH2 and CH3 domains. This suggests segmental gene conversion as the common mechanism of origin.

Base Sequence↗
PubMed1988

Genetics of two human monocyte antigens.

HMA-1 and HMA-2 are two serologically defined alloantigens that are present on human monocytes and granulocytes. Previous panel studies suggested that these two antigens comprise a diallelic system. We therefore performed segregation studies on 10 randomly chosen families and on 22 nucleus families belonging to one large pedigree. All individuals were either positive for HMA-1, HMA-2, or both. Segregation of HMA-1 showed autosomal inheritance with complete penetrance. The cytotoxicity negative, absorption positive (CYNAP) phenomenon sometimes occurred for HMA-2, and because absorptions for HMA-2 could not be performed on all cells, linkage studies were only performed for HMA-1. No linkage of HMA-1 with HLA, immunoglobulin allotypes, granulocyte antigens, or any of the erythrocyte blood groups tested was observed.

Alleles↗
PubMed1988

Further contribution of common Gm*-Am* haplotypes and Km* alleles in the characterization of the Tunisian population.

The Gm, Am and Km allotypes have been investigated in 405 sera from unrelated students and blood donors coming from the different areas of Tunisia. Thirty Gm and fourty-seven Gm-A2m common phenotypes have been observed. Eleven Gm* and seventeen Gm*-A2m* common haplotypes have been deduced from these phenotypes. The Tunisian population appears as mainly Caucasoid (combined frequency of Caucasoid Gm*-Am* haplotypes in the order of 0.81-0.82) with a relatively important Black contribution in the gene pool (combined frequency of Negroid Gm*-Am* haplotypes of 0.17-0.18) and a very low Oriental participation (0.01-0.02). Our results are compared to those previously reported for two other samples of the Tunisian population, the first from the regions of Mahdia and Sfax and the second from several villages of Berbers, the first inhabitants of Tunisia. Likewise, other comparisons are made with populations from Africa, Europe and Asia, since Tunisians are a mixture of Berbers, invaders and immigrants from different origins.

Female↗
PubMed1988

Uncommon Gm* haplotypes in the Tunisian population: further contribution to the genetics of the IgG immunoglobulins.

In this work, eight family studies were conducted to establish the suspected unusual Gm* haplotypes in 13 persons (among 418) showing uncommon Gm phenotypes. Usually, the Gm (21 and 28)--or Gm (g1 and g5)--allotypes are both present or absent. Exceptions to this rule were observed: on the one hand, only the Gm (28) allotype was present in 12 persons, and on the other hand, only the Gm (21) allotype was found in 1 person. Such events could be explained, in some cases, by equal crossovers or point mutations, and, more generally and very likely, by gene conversions. Other interesting results are also presented, as, on the one hand, silent genes homozygous at the C gamma 4 locus and, on the other hand, a homozygous multigene deletion encompassing the C alpha 1, psi gamma, C gamma 2 and C gamma 4 loci.

Chromatography, Affinity↗
PubMed1987

Human leukocyte antigens and immunoglobulin allotypes in head and neck cancer patients with and without multiple primary tumors.

Human leukocyte antigens (HLA) and immunoglobulin (Ig) allotypes were examined in 98 patients with single head and neck cancers, and in 51 patients with multiple primary tumors. Immunoglobulin allotype Km (1) was present in 4% of patients with multiple primary tumors versus 21% in patients with a single head and neck cancer. The frequency of HLA-B8, HLA-DR3, and HLA-DQW2 in patients with multiple primary tumors and of HLA-B8, and HLA-B45 in patients with a single head and neck cancer increased significantly as compared with the control population. Those data suggest genetic influences--next to environmental factors--on the pathogenesis of multiple primary tumors in head and neck squamous cancer. It might be worthwhile to use HLA typing and Ig allotyping in the selection of patients in whom aggressive screening for second tumors is mandatory.

HLA Antigens↗
PubMed1987

Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation.

We have studied the feasibility of using DNA restriction fragment-length polymorphisms (RFLP) to study marrow engraftment in 27 patients after allogeneic bone marrow transplantation, and have compared these results with those obtained using red blood cell antigens, cytogenetics, and immunoglobulin allotypes. Using highly polymorphic DNA probes, we have documented stable chronic mixed hematopoietic chimerism, have identified transient mixed chimeras, have excluded mixed chimerism with high probability in retrospective studies even when a pretransplant DNA sample was not available, have documented marrow engraftment in the early posttransplant period, and have studied the origin of leukemic cells in patients with recurrent disease. We have evaluated the advantages and disadvantages of several genetic markers and have developed tentative statements concerning the prognosis of patients with mixed chimerism. We conclude that DNA RFLP are powerful and practical genetic markers in bone marrow transplantation studies and that further studies of mixed hematopoietic chimerism are warranted.

Antigens, Surface↗
PubMed1987

Susceptibility to multiple sclerosis associated with an immunoglobulin gamma 3 restriction fragment length polymorphism.

Susceptibility to multiple sclerosis (MS) has been linked to the immunoglobulin G (Gm) markers as well as HLA-DR genes. We have used a genomic Ig gamma 1 probe which detects polymorphisms in the gamma 1, gamma 2, gamma 3 and pseudogamma genes to identify restriction fragment length polymorphisms associated with MS. A negative association was found between a 5.9-kilobase (kb) Bst EII gamma 3 fragment and MS. Southern blot analysis of genomic DNA revealed the presence of this fragment in 84 of 140 (60.0%) controls, but in only 17 of 59 (28.8%) MS patients. The frequency of the fragment in 47 myasthenia gravis and 16 Graves' disease patients was similar to that in controls, 60.0 and 62.5%, respectively.

Gene Frequency↗
PubMed1987

Mixed hematopoietic chimerism following bone marrow transplantation for hematologic malignancies.

Twenty-nine of 172 patients (17%) who received an allogeneic bone marrow transplant (BMT) from histocompatible sibling donors for hematologic malignancies were mixed hematopoietic chimeras; ie, they had a mixture of donor and host hematopoietic or lymphohematopoietic cells at greater than or equal to 14 days after transplantation. Twenty-four of the 29 mixed chimeras (83%) have remained in continuous complete remission for up to 116 months (greater than 9 years) following BMT. Four of the 29 patients (14%) have had recurrent leukemia, and 7 of the 29 (24%) have had moderate or severe graft-v-host disease (GVHD). Twelve of these 29 patients have persisted as stable mixed chimeras for greater than or equal to 2 years after BMT, whereas other patients converted to all donor-type hematopoiesis. The incidence of mixed chimerism was independent of the pretransplant regimen, the donor or recipient age (less than 20 v greater than 20 years), remission status (first complete remission of acute leukemia and first chronic phase of chronic myelocytic leukemia v later stages of disease), and type of leukemia. Our data indicate that mixed hematopoietic chimerism is not rare after BMT for hematologic malignancies and that its presence is compatible with long-term disease-free survival. Prospective studies of mixed chimerism after BMT are warranted to achieve better understanding of its biologic importance.

Acute Disease↗
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

Monoclonal antibodies against different domains of human IgA: specificities determined by immunoblotting and haemagglutination-inhibition.

The specificity of 14 monoclonal antibodies has been determined by immunoblotting (IB) and haemagglutination-inhibition (HAI) analysis using IgA1 and IgA2 myeloma proteins and eight different IgA1 fragments. Two antibodies probably recognized epitopes on the CH1 domain of IgA. They reacted with all Fab-containing fragments irrespective of whether these originated from the same or different IgA proteins. Seven antibodies were directed against epitopes on the CH2 domain. These antibodies were reactive with F(abc)2 fragments. They failed to react with Fab, Fab' and F(ab')2 fragments. Two out of these seven antibodies did not react with two-chain IgA half-molecules and Fabc fragments containing a single heavy and a single light chain. This suggests that these two antibodies recognized an epitope whose structure is dependent on disulfide linked heavy chains. Five other antibodies showed specificity for the CH3 domain. They were reactive with all CH3-containing molecules, irrespective of whether they comprised one or two alpha chains. Our study demonstrates that IB is an appropriate technique to determine domain specificity of monoclonal anti-immunoglobulin reagents. Although the IB tests were performed on denatured proteins the results agreed surprisingly well with those of the HAI analyses. Moreover, the IB technique could be used on fragments which could not be purified well enough for HAI analyses.

Antibodies, Monoclonal↗
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

Ig gamma restriction fragment length polymorphisms indicate an ancient separation of Caucasian haplotypes.

This investigation was undertaken to study genetic variation in the human immunoglobulin gamma heavy-chain (IgG) genes using Southern blot hybridization techniques to identify restriction fragment length polymorphisms (RFLPs). A genomic Ig gamma-1 clone was used as a probe, and variants were identified with two restriction enzymes (R.E.), each of which defined RFLPs at two separate IgG loci. Once alleles and haplotypes were determined, molecular localization of the alleles was made through genetic analysis of recombinant haplotypes and through the use of regional specific subclones. Linkage between the newly defined RFLPs and switch region variants as well as protein allotypic markers (Gm) was complete. This analysis included markers for Ig Mu, Alpha 1, Alpha 2, Gamma 1, Gamma 2, Gamma 3, and Pseudo Gamma. The picture that emerges from the molecular study of two common haplotypes, each with many rare variants resulting from recombination or mutation, confirms and extends the earlier immunological observations. The accumulated differences between the two major Caucasian IgG haplotypes indicate that their separation may be ancient and maintained through heterozygote advantage.

Alleles↗
PubMed1985

Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study.

Seventy-four monoclonal antibodies (McAb) of putative specificity for human IgG (11), the IgG sub-classes (59) or Gm allotypes (4) have been evaluated for reactivity and specificity in eight laboratories employing different assay techniques or protocols. For the IgG, IgG3, IgG4, G1m(f) and G3m(u) specificities McAb have been produced that can be satisfactorily applied in most methodologies employed and have potential as reference reagents. The IgG1 and particularly IgG2 specificities proved problematical with all McAb evaluated demonstrating apparent assay restriction and whilst performing well in some assays proved to be poor or inactive reagents in others. However, the study identifies McAb individually suited to application within most commonly employed methodologies. Epitope display is the probable variability rather than capricious behaviour by the McAb. IgG1 and IgG2 were the least immunogenic of the sub-class proteins and there is evidence that epitope display is influenced by the physical and chemical procedures used to immobilize or fix antigen - a common requirement in the assay systems studied.

Antibodies, Monoclonal↗
PubMed1985

Immunogenic and antigenic epitopes of immunoglobulins. X: Monoclonal antibodies specific for human IgA, the IgA1 and IgA2 subclasses and an nA2m(2) iso-allotypic epitope.

Monoclonal antibodies (McAb) specific for human IgA, the IgA1 and IgA2 subclasses and the iso-allotypic epitope nA2m(2) have been produced. Three distinct McAb recognize an IgA1-specific epitope expressed in the C alpha 2 domain or the hinge region whilst a further McAb is directed possibly to an IgA1 hinge region epitope. The McAb having nA2m(2) specificity recognizes an iso-allotypic epitope expressed within the Fab region. IgA1 and IgA2 epitopes were detected in gorilla but not rhesus or baboon sera suggesting that the IgA subclasses represent a recent gene duplication even. However, these epitopes were also detected in some non-primate sera.

Animals↗
PubMed1985

Genetic analysis of eight linked polymorphisms within the human immunoglobulin heavy-chain region.

Genetic analyses of multiple restriction fragment length polymorphisms, revealed by a single DNA probe containing the switch region of the immunoglobulin constant heavy-chain (IgCH) mu gene, are presented here in detail. Five of the polymorphic loci segregate in complete linkage with IgCH allotypic markers, while one appears to be located at more than 10 centimorgans from the IgCH region. A study of over 100 random haplotypes typed at eight linked loci, including the Ig switch polymorphisms and the classical Gm-Am allotypes, allowed us to construct an evolutionary tree by which each haplotypic variant can be derived one from the other either by single-step mutation or by recombination. A few of the recombinant haplotypes appeared to carry large DNA duplications that could be explained by unequal crossing over; others might postulate gene-conversion events. Linkage disequilibria observed between the IgCH-linked loci were compared with expected ones. A heterogeneous distribution of recombination rates is clearly documented, a "hot" region of recombination being present between the gamma 2 and switch alpha 2 loci.

Alleles↗