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.

Localization of J-chain and interchain disulfide bonds in a human F(c)5mu-like fragment.

The inter H-H cysteinyl peptides and the localization of the J-chain were studied in a human F(c)5mu-like fragment. The latter was found to be built up by non-covalent association of molecular forms of 140 000, 95 000 and 70 000 dalton subunits. The trimeric, dimeric and monomeric forms were obtained from gradual reduction by dithiothreitol of the major component of 140 000 daltons, thus confirming the tetrameric nature of this subunit. The latter was found to result from the association of both components of the 70 000 dalton subunit, with the participation of the inter H-H subunit bridge. Structural analysis of the labelled peptides obtained by partial reduction and alkylation showed the presence of the intersubunit disulfide bridge and of the inter heavy-heavy chain bridge of the C-terminal region, and the absence of the heavy-heavy chain bridge of the hinge region. The sequence of these peptides is identical to the sequences of the corresponding peptides of normal mmu-chains. The J-chain, which was covalently linked to this F(c)5mu-like fragment, was found to be predominantly associated within the 95 000 dalton subunit. The results showed that the J-chain was linked in the protein as a "clasp" within a single subunit and not between two subunits.

[Kinetic study of human immunoglobulin G fragmentation by pepsin]. / Etude cinétique de la fragmentation des immunoglobulines G humaines par la pepsine

The rate of pepsin hydrolysis of the four subclasses of human IgG has been studied. The levels of undegraded IgG and of pep-F'c fragments have been determined by radial immunodiffusion using specific antisera against Cgamma2 and Cgamma3 domain antigenic determinants. This study shows that the four IgG subclasses have different susceptibilities to pepsin hydrolysis and defines the optimum conditions (times of hydrolysis) for the preparation of maximum yields of F (ab)'2 fragments and/or pep-F'c fragments.

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.

[Preventive treatment of infection caused by gram-negative bacteria using anti-lipopolysaccharide antibodies. Evaluation in patients with aplasia]. / Traitement préventif des infections à bacille à Gram négatif par des anticorps anti-lipopolysaccharides. Evaluation chez l'aplasique.

The prophylaxis of severe Gram-negative infections with human antiserum to lipopolysaccharide (LPS) was evaluated in a randomised study of 60 patients with therapeutic aplasia for leukaemia. The antiserum was found to be ineffective in preventing Gram-negative infections. The levels of anti-LPS antibodies showed that passive immunization was obtained in only one half of the patients. These disappointing results warrant further investigations to evaluate the effectiveness of this prophylactic treatment.

[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.

[Deficiency of alpha-1-antitrypsin and the allele Pi nul]. / Le déficit en alpha-1-antitrypsine et làlléle Pi nul

Alpha-1-antitrypsin is a glycoprotein in human serum that inhibits several proteases. It is a polymorphic protein. A single autosomal locus (Pi), with multiple codominant alleles is responsible of the synthesis of alpha-1-antitrypsin. Of particular interest are alleles that lead to lower than normal concentrations of alpha-1-antitrypsin in serum, namely, PiS, PiP and PiZ. Some of these subjects carry a high risk of developing chronic obstructive pulmonary disease, especially when they are homozygotes for PiZ. In children, cirrhosis of the liver are also found in association with homozygosity for PiZ. recently, TALAMO discovered a subject whose serum contained no alpha-1-antitrypsin; this was the first case of total deficiency, and the patient carried a double dose of the so-called Pi--allele (Pi nul). We were able to demonstrate that a single dose of this allele exists in three families which we have studied in this paper. In a fourth family, the propositus carries Pi-- in duplicate. We report here the second case of the strange homozygous phenotype, Pi--. Surprisingly, we have found that alpha-1-antitrypsin is not completely absent in this serum; its concentration is 200 times lower than normal (less than 10 microgrammes per ml). At the moment, the existence of the Pi-- allele is obvious, but the significance of this small quantity of alpha-1-antitrypsin in the serum of such a patient remains unknown.

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.

[The effect of certain anti-HL-A alloantisera on human lymphocyte receptors for the Fc fragment of IgG]. / Action de certains allo-antisérums anti-HL-A sur les récepteurs des lymphocytes humains pour le fragment Fc des IgG

A procedure of EA rosette formation inhibition is used to show an effect of anti-HL-A alloantisera on human lymphocyte Fc receptors. IgG and F(ab')2 fragments also inhibit EA rosette formation. A relationship between Fc receptors and antigens recognized by these antibodies is suggested.

Demonstration of the Rhesus haplotype CdE (r-y) in the genotype of 48 subjects from 8 families. Genotype CdE/CdE (r-yr-y) in 2 members of the same family.

Forty-eight individuals heterozygous for CdE (R-Y) haplotype were identified in the pedigrees of 8 kindreds containing 128 members. Two homozygotes CdE/CdE (r-yr-y) were found in a large inbred kindred. Our study among French blood donors of the Seine-Maritime region demonstrated that about one of two individuals possessing the Rhesus phenotype CcdEd (rh'rh') carried the CdE (r-y) haplotype.

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.

Does alpha-1-antitrypsin P1 null phenotype exist?

A second case of Pi null alpha-1-antitrypsin (AA) deficiency is described. In fact, the serum's subject contains 5 mug of AA per millilitre. With radiolabelled specific antibodies, it is possible to describe the Pi phenotype associated to this deficiency. The pattern which is obtained is like the ordinary Pi M, but 500 times lower than normal values. In contrast to a common deficient variant (ZZ or MZ), the subject tissues do not contain periodic acid-schiff positive inclusion bodies. The "normal" pattern obtained after antigen-antibody crossed electrophoresis, would be in favour of a deficient anomaly hereditarily transmitted.

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).