IgG4 subclass in malignant melanoma.

Three hundred and ninety-seven sera from 185 melanoma patients were studied. These sera were classified into three groups according to stage of disease. An alteration in the level of the IgG4 subclass was found. It was related to the dissemination of disease. The percentage of abnormalities (either increased or decreased levels of IgG4) was more frequent in patients with stage II and III diseases (55 and 53%, respectively) than in patients with stage I(19%). The higher frequencies of high titers of IgG4 were essentially detected in advanced disease. The biologic significance of the increase of IgG4 in melanoma remains obscure. The increase may be related to the development of facilitating antibodies of the IgG4 subclass.

Quantitative studies of Gm allotypes. I. Reappraisal of the method using an autoanalyzer.

In this study, various parameters for the autoanalyzer hemagglutination-inhibition circuit applied to Gm studies, were examined. Details are given of modifications of this circiut and related methodology, that improve its precision and the reproducibility of results: use of a cells counter, effects of temperature, PVP, Tween 20, anti-Gm concentration, etc. The effects of age, storage and freezing on quantitative Gm allotypes antigenicity are also stressed.

[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.

[IgG levels in the sera of melanoma patients (author's transl)]. / Etude des IgG dans les sérums de 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 IgG4 subclass 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.

[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.

An abnormal Cgamma 4 gene among the negro population.

An analysis of the IgG4-CH3 antigenic determinants by means of specific antisera using a hemagglutination-inhibition procedure among different populations has been done. Thus 3.67% of sera from Negroids have been found completely deficient in normal IgG4 subclass. Sera without normal IgG4 contained the other IgG subclasses. Family studies shown the transmission of an abnormal Cgamma 4 gene. Hypothesis of gene deletion, point mutation or gene hybridization were postulated. This last hypothesis seems the most valuable.

[Antigenic determinants of human immunoglobulin light and heavy chain variable regions. Comparison with animal species]. / Déterminants antigéniques des régions variables des chaines lègéres et des chaines lourdes des immunoglobulines humaines: étude dans différentes espèces animales

An antigenic analysis of human heavy and light chain variable region subgroups has been done on different animal species, by means of heterologous specific antisera using a hemagglutination-inhibition procedure. Excepted in lemur sera, where Vkappa III and Vlambda III are the only variable antigenic determinants found, all VL antigenic determinants tested were shown to be present in primates. In other mammals (carnivores, some rodents, some artiodactyls) several VL antigenic subgroup determinant were detected while others were not. No VL antigenic determinant was found in other classes studied. The VH III subgroup antigenic determinant was found among all primates, some mammals and avains. The results suggest that there has been more preservation in the variable region of immunoglobulin chains, and particularly VH III chain, than in the constant region of immuoglobulin molecule.

Heavy and light chain variable region subgroups: antigenic analysis among human monoclonal immunoglobulins.

An antigenic analysis of human heavy and light chain variable region subgroups has been possible by means of heterologous specific antisera using a hemagglutination-inhibition procedure. The specificity of antisera had been shown to be directed against antigenic determinants of VkappaI, VkappaII, VkappaIII, VlambdaI, VlambdaII, VlambdaIII and VHIII by means of chemically subgrouped proteins. A series of IgG, IgA, IgM and IgD were examined for the presence of a VHIII variable region subgroup antigenic determinant. The data showed that 50% IgG, 62% IgA, 55% IgM, 45% IgD were positive for VHIII antigenic determinant. NH2 terminus blocked monoclonal immunoglobulin belonging to the VHIII subgroup were found, increasing incidence of this subgroup among IgG. A preferential association of VHIII antigenic determinant with IgG1, IgG3 subclasses was observed among IgG myeloma proteins while the preferential association was only observed with IgG1 subclass when anti-Rh antibodies were considered. Among 53 IgG of kappa type 20 (37%) kappaI, 30 (56%) kappaII, 3 (5%) kappaIII subgroups were found and among 42 IgG of lambda type 13 (31%) lambdaI, 13 (31%) lambdaII and 16 (38%) lambdaIII were observed. Although numbers are limited in each group for conclusions a study of VHIII and non VHIII antigenic subgroup determinant with respect to the light chain subgroups is given. The non-allelic behaviour of this VHIII antigenic determinant was observed. Preliminary data on the presence of these human antigenic determinants among different animals species were given.

Antigenic determinants of heavy chain variable regions: immumological typing of the human immunoglobulin VHIII subgroup.

An antigenic determinant of the VHIII variable region subgroup was defined by means of a heterologous specific antiserum using a hemagglutination inhibition procedure. The specificity of this antiserum was established in inhibition experiments with proteins either of known primary structure or belonging to a definite VH subgroup. A series of IgG, IgA, IgM and IgD monoclonal proteins was examined for the presence of this VHIII subgroup antigenic determinant. The data showed that 50% of the IgG, 62% of the IgA, 55% of the IgM and 41% of the IgD were VHIII-positive, and that certain "blocked" monoclonal immunoglobulins belonged to this subgroup. A preferential association of the VHIII antigenic determinant with the IgG1 and IgG3 subclasses was observed among IgG myeloma proteins while the preferential association was only observed with the IgG1 subclass when anti-Rh antibodies were studied. The VHIII subgroup exhibited nonallelic behavior.

Gm and Inv allotypes in premature infants.

Using haemagglutination inhibition tests specific for Gm allotypes and similar tests for IgG4, the placental transfer of the four IgG subclasses from mother to foetus has been confirmed. The Gm phenotype of a cord serum is often identical to that in the corresponding maternal serum. However in 31 cases out of the 90 tested, Gm allotypes were present in the cord serum that were not present in the maternal serum. These allotypes produced by the foetus in utero are dependent on a paternal gene. The logarithm of the IgG level increase proportionately with gestational age (r = 0.59 p less than 0.001).

Deletion of hinge region of human myeloma IgG1 molecule (protein LEC) associated with nonexpression of G1m (3) and Km (1, 2) allotypes. A possible genetic explanation at the DNA level.

In this paper we report the structural basis for the nonexpression of G1m(3) and Km (1,2) allotypes in an IgG1 (kappa) human myeloma protein (protein LEC). Heavy and light chains spontaneously dissociate in sodium dodecyl sulfate polyacrylamide gels. Light chains appear to be covalently S-S bonded. Analysis of cysteine-containing peptides shows that the heavy chain of the IgG protein LEC has a deletion of residues 216-230, thus encompassing the entire hinge region. An arginine residue, characteristic of the G1m(3) marker is present at position 214. An alanine at position 153 and a leucine at position 191 of the light chain, characteristic of the Km (1, 2) allotypes, are present. It is likely that the double Km and Gm lack of expression is the result of the deletion. The genetic implications of the sequence of this protein are discussed.

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.

[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.

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.

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.

Evidence for "deleted" or "silent" genes homozygous at the locus coding for the constant region of the gamma3 chain.

Three uncommon stable Gm haplotypes, Gm3;23;--, Gm1,2,17;..;-- and Gm1,17;..;-- have been transmitted through 3 generations of two related Lebanese and Syrian families. No pathological consequence was noted in seven individuals, aged 14--65, whose sera were deficient for all the allotypes carried by the IgG3 chains. Among the different genetic events which could have produced these haplotypes (alteration of a regulatory gene, point mutation, gene hybridization, gene deletion), it appears that a structural deletion is the most probable explanation. The observed data can be explained by either a partial or a total deletion of the constant portion of the IgG3 heavy chain.

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.