Interactive effect of HLA and Gm tested in a study of 135 juvenile insulin-dependent diabetic families.

Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes (IDD) has been studied in 135 IDD families comparing HLA and Gm phenotype distributions in patients and sibling controls. The association analysis comparing the 135 index cases to 124 sibling controls did not show any significant interaction, but only a tendency for Gm 4,5 phenotypes to be more frequent in IDD patients, particularly in those who carried DR3/X. The sib pair analysis of 16 pairs of affected sibs did not show any distortion of segregation of Gm. On the other hand, among 98 sib pairs of one affected and one nonaffected sib, there was a significant distortion in favour of sib pairs with non-identical Gm phenotypes. However, no interaction between HLA and Gm was found. These results provide suggestive evidence that Gm or a locus very close to Gm could be involved in susceptibility to IDD.

The amino acid sequence of a lambda light chain presenting abnormal physicochemical and antigenic features.

The amino acid sequence of the light chain of a human monoclonal IgA1 (Mem) was established, in part by analogy with already known sequences. By homology its variable part was shown to belong to the V lambda I subgroup while the isotype-associated amino acid residues characterized it as Mcg+, Kern+ and Oz-. The normal primary structure of this chain was in contrast to its abnormal physical and antigenic properties: (a) its apparent molecular mass estimated by SDS/polyacrylamide gel electrophoresis, by gel filtration chromatography and by gradient ultracentrifugation was found to be lower by approximately equal to 10% than the values (23.5 kDa) of 'normal' light chain used as controls; (b) the lambda I chain Mem, when tested in native state was not antigenically reactive. These abnormalities were reverted when the chain was treated with 8 M urea. These data suggest that the abnormal behaviour of lambda I chain Mem is at a conformational level.

HLA, Pi, Gm and Km phenotypes in a spina bifida population with myelo-meningocele.

HLA, Pi, Gm and Km phenotypes were determined in 53 cases of spina bifida with myelomeningocele. Family studies were possible in 42 cases. An increase in the frequency of HLA-B5 antigen was found. Some phenotype frequencies were also increased without reaching significant levels.

Quantitative studies of Gm allotypes. V. Simultaneous presence of latent Gm allotypes and deficient Gm genes in a family with hypogammaglobulinaemic probands.

A study of Gm allotypes in a Caucasoid family with hypogammaglobulinaemic probands, showed qualitative (unexpected or lacking Gm allotypes) and quantitative (increased or decreased Gm contents) abnormalities in many relatives. Part of these observations can be most probably accounted for by inheritance of a GM1,17; 5,28 haplotype, not described in Caucasians yet, and by an in vivo expression of latent Gm genes.

Frequencies of Gm and Km allotypes in the population of Singapore, Sri Lanka and Punjabis in North India.

Serum samples from Sinhalese subjects, from Punjab and from Singapore have been studied. The Gm phenotypes found are very numerous and we can observe some similarities concerning the Gm gene frequencies between the Singapore Indians with the Indians of North India, and with the Sinhalese. In contrast, Gm gene frequencies found among Chinese and Malays from Singapore are quite different from those found among Indians of Singapore. Our results here are very similar to those obtained in Malaya studies.

[Exclusion of MNSS, Kidd and Gm from the extreme end of the short portion of chromosome 8]. / Exclusion de MNSs, Kidd et Gm de l'extremite du bras court du chromosome 8.

11 blood and seric group markers were studied in a case of 46,XX,del(8)(qter yields p22 :) in order to contribute to the exclusion map. MNSs and Jk are informative and could be excluded from the region. The proband is also definitly heterozygous for immunoglobulin Gm groups which were tentatively assigned to the short arm of chromosome 8 or 12.

Genetic study of the Cuiva Indians of Venezuela.

Serum and red cell protein markers were investigated in Cuiva Indians. Our ethnologic studies indicate that the low degree of genetic variability in this population is probably due to genetic drift.

Gm, Am and Km immunoglobulin allotypes of two populations in Tunisia.

Gm, Am and Km allotypes were investigated in two Tunisian populations (236 samples from Mahdia and 142 samples from Sfax). These populations descend from immigrants and, therefore, the results were compared with those obtained in other populations living in the Near East and in North Africa. The subclass heavy chain allotypes G1m, G2m, G3m and A2m are inherited in fixed combinations. There were five main and four minor Gm-Am haplotypes that could be deduced from the phenotypes. This led to the conclusion that the populations studied are Caucasoids with some African admixture (about 10%) and a very low oriental contribution. Furthermore, there were 11 samples which showed 8 uncommon Gm-Am phenotypes. These could be explained by the assumption of five different uncommon Gm-Am haplotypes. Four of these may have arisen by equal crossing over of prevalent haplotypes. The fifth may be the result of unequal crossing over of prevalent haplotypes. The fifth may be the result of unequal crossing over, since it was proven, by family study, that more markers are transmitted together than are present in the prevalent haplotypes.

Familial occurrence of monoclonal gammapathies.

The purpose of this work was to evaluate the genetic propensity importance in the monoclonal gammapathies occurrence. Systematic serum-electrophoreses were performed on 172 relatives of 37 reported patients and on 10,784 controls over 30. The 4 families including one or more "paraproteinemia" other than the proband's were investigated. Experimental, epidemiologic, immunologic and genetic arguments are discussed.

[Urinary evaluation of 5-S-cysteinyldopa and seric evaluation of IgG4 subclass during follow-up of 27 primitive malignant melanomas (author's transl)]. / Dosage urinaire de la 5-S-cystéinyldopa et dosage sérique de la sous-classe IgG4 au cours de la surveillance de 27 cas de mélanomes malins primitifs.

27 patients with SSM or NM level IV and V have been submitted to a monthly evaluation of their level of 5-S-cysteinyldopa in the urine and IgG4 subclass in their sera. For 5 patients who entered the stage II of their disease during the follow-up, 3 had elevation of the 5S and 5 had large variations of IgG4. On 21 patients in clinical remission, 10 had conjunctly an increase of 5S and variations of IgG4. The predictional value of these tests is discussed.

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.

[Gm(28), a new allotypic marker on human IgG3: peculiar interest of its study within Negroid populations (author's transl)]. / Gm(28), un nouvel allotype du système Gm présent sur les IgG3: intérêt particulier de son étude dans les populations négroïdes.

A new allotype in the Gm system (Gm(28)) was described and studied. Among Caucasoids and Mongoloids, it was found with rare exceptions, in samples containing Gm(21), segregating with Gm1,17,21 and Gm1,2,17,21 haplotypes. This new antigenic determinant was found to be of particular interest among Negroid populations in which its frequency is variable. It can be detected with all--common or uncommon--haplotypes. The degree to which it is associated with some haplotypes in different populations may prove useful in the characterization of Negroid populations. This new allotypic determinant is located on the CH3 homology region of IgG3 subclass.

Immunoglobulin Gm and Km genetic markers in Vietnamese.

The distribution of the G1m (1,2,3,17), G2m(23), G3m(5,10,11,13,14,15,21,28) and Km (1,2) allotypic markers has been examined in 122 unrelated Vietnamese subjects originating from all regions of Vietnam. The 13 observed phenotypes have been explained by means of 8 haplotypes: 5 'major' ones (which are also known to be usual in all other reported Mongoloid populations) and 3 'minor' ones. Consideration of gene frequencies allows easy integration of Vietnamese within the south-north cline of Gm haplotype distribution in East Asia, where they insert between Southern Chinese, on one hand, and Singapore as well as South Central Chinese on the other hand. The observed Km10.290 frequency value revealed to be of the same order of magnitude as the values reported for most other non-Thai Mongoloids.

Quantitative studies of Gm allotypes. II. G1m(1), G3m(5) and G3m(21) in sera from healthy caucasoid blood donors, and in a family with the inheritance of a gene responsible for a weak Gm1,17;..;21 haplotype.

The quantitative expression of three allotypes--G1m(1), G3m(5) and G3m(21)--has been studied in normal caucasoid sera. A gene dosage effect, previously described for all of these allotypes, is not noticed for G3m(5) in the present study. The different content of G3m(5) and G3m(21) IgG3 molecules in heterozygous Gm5/Gm21 sera has been verified: these contents are respectively 75% and 25% of the IgG3 content. The same allotypes have been studied in a family which shows the inheritance of a weak Gm1,17;21 haplotype. The gene responsible for this abnormality is probably a new regulatory gene, and is transmitted without the 'aimed' haplotype.

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.

[IgG levels in the sera of melanoma patients (author's transl)]. / Etude des IgG dans les sérums des sujets porteurs de mélanomes.

397 sera from 185 melanoma patients have been tested. We classified our subjects into three groups, according to the stage of disease. An alteration of the level of IgG 4 sub-class was found and related to the extension of the disease. The percentage of abnormalities was more frequent in stage II and III (55 p. 100 and 53 p. 100) than in stage I (19 p. 100). High titers of IgG 4 subclass were essentially detected in advanced disease. The biological significance is discussed.