[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 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.

[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.

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.

[IgG subclasses in malignant melanoma]. / Etude des allotypes Gm et des sous-classes d'IgG chez des sujets porteurs de mélanomes malins

The 397 sera from 185 melanoma patients have been studied and classified in three groups according to the stage of disease. Our findings revealed an alteration of the level of IgG4 subclass which is related to the dissemination of disease. The percentage of abnormalities (either increased or decreased levels of IgG4) was more frequent in stage II and III (55% and 53% respectively) than in stage I (19%), The higher frequencies of high titers of IgG4 were essentially detected in advanced disease. The biological significance of the increase of IgG4 in melanoma remains obscure. It may be related to the development of facilitating antibodies of IgG4 subclass.

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.

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.

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.

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.

[Rheumatic manifestations in 80 cases of Crohn's disease]. / Manifestations rhumatismales dans 80 cas de maladie de Crohn

Out of a series of 80 patients suffering from Crohn's disease, 31 presented rheumatic manifestations. In 16 subjects this took the form of synovitis closely dependent on the enteritic evolution, which developed after the alimentary symptoms, and which worsened as they did and sometimes regressed as they did following medical or surgical treatment. In combination with erythema nodosum, aphtosis, and conjunctivitis, synovitis appears to be the expression of an immune response to the enteritic lesion. Three cases of chronic polyarthitis and 6 cases of asymptomatic sacro-ileitis were also observed, and 6 cases of spondylarthritis of a minor radiological type were observed that evolved independently of the Crohn's disease. Typing according to the HLA system using 26 antigens was carried out in 44 subjects; no difference in phenotype frequency was found between a control group (blood donors) and the group of subjects with Crohn's disease alone; however, the antigen W 17 was found significantly more frequently in those subjects with peripheral arthritis and the antigen W 27 was found more frequently in those with spondylarthritis. These findings suggest, although it is not certain, the existence of genetic susceptibility to rheumatic manifestations in certain sites in patients with Crohn's disease.

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.

Definition in man of a polymorphic system of the normal colonic secretions.

A study conducted in 30 normal human colons, obtained from cadaveric kidney donors, has evidenced the presence of two polymorphic antigenic specificities, W and Z, in the secretory cells of the colon mucosa. Three phenotypes have been demonstrated so far: W-Z- (frequency: 0.17), W-Z+ (frequency: 0.23), and W+Z+ (frequency: 0.60). Specific anti-WZ and anti-W alloantibodies, independent of anti-A and B agglutinins, were found in normal sera from blood donors. No apparent correlation was found between the WZ specificities and the ABH Lewis specificities, the other blood group systems specificities, and the leucocyte group (HL-A) specificities.

[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.