An improved three-step method for the purification of the third component of human complement.

This paper describes a three-step purification method for the third component of human complement (C3) from plasma. The method consists of PEG precipitation, DEAE-cellulose chromatography and preparative isofocusing in a granulated dextran gel, with pH range 5--8. From this last step, a highly purified form of native C3 was obtained as indicated by immunoelectrophoresis and polyacrylamide gel electrophoresis analysis. The average final recovery was 20%.

[Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes]. / Interaction entre HLA et Gm pour la susceptibilité au diabète insulino-dépendant.

It is now well established that HLA system is involved in the susceptibility to Type 1 diabetes mellitus. In this study we look for a possible effect of the Gm system. A first study (cases-controls) suggests that among individuals who had HLA-DR3 but not HLA-DR4 or HLA-DR4 without HLA-DR3, there is a possible effect of the phenotype Gm3,23,5 or Gm3,-5 in the susceptibility to IDDM. Moreover, we have tested by the sibpair method whether HLA and Gm are transmitted independently from IDDM: an unaffected sib, sharing the same HLA haplotypes than an affected individual, seems to be more often phenotypically different at the Gm loci.

Allotypic variants of human C3 and properdin factor B in two French populations Normans and Basques.

Human Properdin factor B and C3 polymorphisms are of a real usefulness as genetic markers for population studies. In addition, they are more and more used for the determination of paternity cases. The present communication will be about Bf and C3 allele frequencies in two locally populations of France, Normandy and Western Pyrenees (Basques), The corresponding allele frequencies are as follows, for Normans : Bf(S) = 0.7422, Bf(F) = 0.2285, Bf(F1) = 0.0205, Bf(SO.7) = 0.0088; CsS = 0.788, C3F = 0.204, C3Srare = 0.004, C3Frare =0.004; and for Basques : BfS = 0.5625, BfF = 0.305, BfF1 = 0.1235, BfSO.7 = 0.0075; C3S = 0.7075 and C3F - 0.2925. French Basques are characterized by unusual allele frequencies in European Caucasoid populations for Bf as for C3 genes. A very high incidence of BfF1 allele is reported (BfF1 = 0.125), as previously observed [7, 17].

Influence of IgG subclasses on automated anti-D (Rho) quantification.

Anti-D quantification by both an automated Polybrene method and an automated trypsin-albumin-dextran (TAD) method gave discrepant results in certain cases. These discrepancies, expressed as the polybrene TAD ratio of reactivity (PTR), were related to the IgG subclass of anti-D. Anti-D of the IgG3 subclass showed a higher PTR than IgG1 (0.94 vs 1.65). No difference was shown between G1m(1) and G1m(3) (0.93 and 0.95, respectively) or between G3m(11) and G3m(21) (1.40 and 1.81, respectively) allotypes. The simultaneous use of our automated Polybrene and TAD methods provides information about the anti-D subclass composition.

Studies on an isolated West Indies population. VI. Immunoglobulin (Gm and Km) allotypes.

A random sample of 221 individuals taken from 2000 inhabitants of a small Caribbean island of French origin were typed for Gm and Km allotypes. Gm haplotype frequencies were found to be significantly different from France. Km(1) frequency was found to be lower than in the French population. These differences suggest a small degree of admixture with the Black population, and genetic drift.

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.

The incidence of Gm and Km allotypes in a group of Bretons, the Bigoudens.

Immunoglobulin allotypes were studied in a peculiar Breton community, the Bigoudens. Results showed that the incidence of the common Gm and Km phenotypes fell into the ranges quoted for Caucasian populations, except for the Gm1;..;5,10,11,13,14 and Gm1,2;..;5,10,11,13,14. The frequencies were found to be significantly different from those of non-Bigouden Breton neighbouring controls.

Deleted IgG1 and IgG2 H chains in a patient with an IgG subclass imbalance.

The serum of a female patient studied over 7 months initially showed, in addition to normal residual IgG, two abnormal IgG proteins and in the last 3 months of the disease showed only one abnormal IgG protein. Gm typing and serological subclass determinations revealed an imbalance of allelic forms within the IgG1 subclass during the disease. The IgG2 level remained markedly elevated throughout the study. The two abnormal IgG-related proteins were devoid of light chains. The abnormal gamma cathodic immunoglobulin and the abnormal beta 2-immunoglobulin were Fc-like and covalently disulphide linked, with molecular weights of 60,000 daltons (N terminal, SER) and 72,000 daltons (N terminal, GLY) respectively. The first belonged to the IgG1 subclass and the second to the IgG2 subclass. No abnormal proteolytic activity was noted and plasma cells reacted with anti-gamma-chain antisera only. We hypothesize that the molecular defect leading to the deleted chains was an early event, preceding the differentiation into plasma cells which produced the two IgG1 and IgG2 deleted H chains.

Nonorgan-specific autoantibodies and immunoglobulin allotypes in relatives of patients with monoclonal gammopathy.

Polyclonal immunoglobulin increase, rheumatoid factor, antinuclear antibodies and cold lymphocytotoxins were detected 10, 8, 7 and 8 times, respectively, in a group of these informative families (22, 17 and 29 subjects tested, respectively). Each family included at least 1 subject with a monoclonal gammopathy in addition to that of the proband. No correlation could be shown between any of these abnormalities and Gm haplotypes. Nonetheless, it is worth noting that 6 out of 41 relatives under 30 years of age had cold lymphocytotoxins.

The variable region of human immunoglobulins. I. Serologic and structural correlations of antigenic markers common to V lambda I and V lambda IV proteins (isotypic cross-reactivities).

Sixty-eight human lambda-chain sources including representatives of the five different subgroups were studied for the distribution of the serologic markers ST, 111, and VOR The variable region character of these antigenic determinants has been demonstrated for those proteins whose primary structures had been partially or completely determined previously. The lambda-chain sub-groups I and IV are readily distinguished antigenically but the specificity designated VOR is shared between them and is absent in the II, III, and V subtypes. The results of these studies are discussed with respect to the possible relationships of the structural genes controlling the synthesis of the lambda-chain subgroups, and some potential phylogenetic and functional meaning of the heterogeneities is revealed.

IgG (Gm) allotypes and multiple sclerosis in a French population: phenotype distribution and quantitative abnormalities in CSF with respect to sex, disease severity, and presence of intrathecal antibodies.

The association of a given Gm allotype or phenotype with MS susceptibility, as previously described in some Caucasian populations, was not observed in a large French MS group, whether or not considering the possible influence of sex or disease severity. This result could be related to variations in geographical distribution of Gm alleles and MS susceptibility gene(s) or suggests the simultaneous involvement of Gm and other genetic system(s). In contrast, the corresponding CSFs exhibited already known MS-associated abnormalities of IgG1 (G1m) allotype contents, which therefore did not merely result from a Gm-associated MS susceptibility. These quantitative abnormalities were not sex dependent, but may fluctuate with MS severity. The G1m allotype levels in each CSF were not correlated with titers of various intrathecal antibodies but with the number of antibody specificities detected, a picture arguing for a polyclonal, non-antigen-specific activation of G1m allotype-producing B cells present in MS brain.

Genetic study of Tunisian Berbers. I. Gm, Am and Km immunoglobulin allotypes and ABO blood groups.

The Gm, Am and Km immunoglobulin allotypes and ABO blood groups were studied in three groups of Tunisian Berbers . The results showed that the actual Berbers of Tunisia present certain heterogeneity and their ancestors were probably the first inhabitants of North Africa. Indeed, although their Gm-Am haplotypes are mainly Caucasoid, some of them are typically African. The group of Kesra village, the most Caucasoid, shows frequencies of Gm-Am haplotypes very close to those of South European populations, particularly the Spanish, who are probably of the same origin. The gene frequencies of the ABO groups in the three Berber groups were similar to those recorded in European populations with a relatively high frequency of the O genes typical of the Berbers .