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Diffuse skeletal muscle enlargement appeared in a 62 years old male without any detectable endocrine disturbance. The patient's weakness contrasted with his athletic appearance. There was no myotonia nor fasciculations. The laboratory investigations were unrevealing until 18 months after the apparent beginning of the disease: free kappa light chains in serum and urine and plasmocytosis in the bone marrow established the diagnosis of multiple myeloma. No amyloid infiltration was observed on the biopsied tissues: skin, muscle and tongue. The diameters of the muscle fibers were at the upper limit of the normal range. There was no fiber type grouping. Kappa light chain deposits surrounding the muscle fibers and numerous coated vesicles beneath the sarcolemmal membrane were found by electron microscopy. The patient's serum was tested on human muscle cell cultures and displayed trophic properties for these cells. This effect was not due to an acceleration of the myoblast proliferation, but to an enhancement of their differentiation. The fusion was more rapid than in presence of control serum and lead to larger and highly branched myotubes. Protein synthesis was increased as demonstrated by the significantly higher 3H-leucine incorporation into the trichloroacetic-acid precipitable material. An identical trophic effect was also found with the kappa light chains purified from the patient's serum but only in the presence of normal human serum.

Studying the lipids bound on normal and myelomatous IgG, we have compared, using gas-liquid chromatography, the fatty acids extracted from untreated proteins, from papain hydrolysis and from Fab and Fc fragments. These last have been purified with affinity chromatography. We have been able, using mass spectrometry, to identify one of the various unknown compounds: it is di-octyl-phthlate.

A 76-year-old woman was hospitalized for stabilization of her diabetic condition. The results of radiological, hematological, and biochemical investigations suggested the diagnosis of an IgD myeloma. A specific immune-serum was used to demonstrate the presence of monoclonal protein of the IgD lambda type. The course of the disease was very rapid and death occurred within 19 days from acute renal failure. The authors emphasize the various factors demonstrating the original nature of this observation and conclude by insisting on the necessity to use anti-heavy chains delta and epsilon during the diagnostic investigations for minoclonal gammapathies.

Site Pg is an antigenic determinant which is present on the surface of serum lipoproteins and reacts with an antilpoprotein myelomatous immunoglobulin, the IgA, Ger. Firstly site Pg is extracted from LDL with the major part of lipids, by an ether-methanol mixture at 6 p. 100. Then the organic substrate obtained is evaporated under vacuum and dissolved in saline before being submitted to an extraction by ehter only. Under these conditions, site Pg remains in the aqueous phase. A polyacrylamide gel filtration on Biogel P2 allows then to separate the substance which reacts with IgA Ger. anti-Pg, from the aqueous phase. The identification of site Pg allowed us to recognize the presence of galactose, phosphorus and choline, and to evaluate its molecular weight of about 330. The reactivity of site Pg with IgA anti-Pg was measured by inhibition of passive hemagglutination and fluorescence quenching. The association constant of site Pg with the whole IgA Ger. or with its Fab fragment could thus be calculated (1.6 10(5) M-1 with the whole IgA; 2.3 10(5) M-1 with the Fab fragment). We showed also that if phosphorylcholine plays an immunodominant role, the presence of sugar seems necessary, since the association constant of the whole IgA Ger. with site Pg is higher than that of IgA Ger. with phosphorylcholine alone.

The carbohydrate composition of an human IgM myeloma protein (IgM Du) has been determined. Seventeen homogeneous glycopeptides are described and exhibit a very large microheterogeneity. They appear as two different groups : the first one contains only mannose and N-acetyl glucosamine, while the other contains N-acetyl-glucosamine, mannose, galactose, fucose, and sialic acid in variable amounts. One glycopeptide termed IX1, which contains 6 mannose and 1 N-acetylglucosamine residues is located on the terminal portion of the Fc fragment and its aminoacid sequence has been determined : Tyr-Asx-Val-Ser.

In this method, under certain experimental conditions, the use of calibrated glass beads permitted the separation of lg with antilipoprotein antibody activity (HLAA). The sera are first precipitated on ammorium sulphate at 25 per cent, 30 per cent and 40 per cent saturation. The precipitates are then submitted to short ultracentrifugation and the product of ultra-entrifugation is fractionnated on a glass bead column, balanced then eluted with an acetate veronal buffer at pH 9. The eluted fraction in peak 1 contains antibodies (IgG or IgA) and albumin. Passive hemagglutination with red cells covered with beta and alpha-lipoproteins, through chromium chloride, together with inhibition of the reaction show that the activity of these Ig antibodies is directed against lipoprotein antigens.

Investigations performed in a patient with myeloma, hyperlipidemia, and xanthomatosis demonstrated the antilipoprotein activity of the monoclonal IgA directed against an antigenic site--called Ra.--different from those previously described. A complex IgA beta-lipoprotein has been firstly characterized. After isolation and purification of the IgA, it has been shown that the association between IgA and lipoprotein was immunologically mediated. The antibody is an IgA lambda bound via its Fab portion and in fixed combining ratio to an antigenic determinant shared only by LDL and VLDL of humans and some other mammalians to the exclusion of any other serum proteins. The results obtained with passive hemagglutination and inhibition of hemagglutination suggest that the antigenic site Ra. is not located on apoprotein B (major proteic moiety of LDL and VLDL), since the antigenic determinants of apolipoproteins are different in humans and in animals and since IgA Ra. fails to react with apolipoprotein B obtained by delipidation of LDL. On the other hand, the lack of reaction between IgA Ra. and HDL suggests that the antigenic determinant is not only present on the lipid hapten such as in the case of PG and AS determinants which are located on VLDL, LDL, and HDL from humans and animals. So the antigenic determinant revealed by IgA Ra. seems to be different from those previously described.

We described a rapid and sensitive method for urinary proteins disc-electrophoresis on unconcentrated urine, by using polyacrylamide-SDS gel in discontinuous gradient. Correlation with a conventional polyacrylamide agarose slab electrophoresis on concentrated urine is good, our technique being more sensitive when proteinuria is low. It had proved to be useful for routine detection of renal failures in clinical laboratories.

Syngeneic mice of the C3H/He strain have been inoculated with cells of the plasmocellular tumours X5563 and X5647, producing myeloma proteins of the IgG and IgA class respectively, and were immunized with (1) sheep red blood cells, (2) bovine serum albumin and (3) horseradish peroxydase. The immune responses of the various groups of mice were followed. The antibody activities towards all three antigens were decreased in mice carrying the IgG producing tumour X5563. This effect was correlated with an enhanced catabolism of IgG as well as with a decrease in number of IgG antibody producing cells. A reduced immune response was also observed in mice to which the IgA producing tumour X5647 had been transferred, but the effect was significantly less pronounced. There was no effect at all observed on the IgM response. The avidity which was measured for the various IgG antibodies was not modified by the presence of IgG nor IgA secreting myeloma tumours.

The author reviews the present state of knowledge of value in rheumatology concerning serum immunoglobulins, their structure, their cellular biosynthesis, and their relation to membrane immunoglobulins of the B lymphocytes. He then examines the concept of dysglobulinaemia and explains why the terms monoclonal immunoglobulin and monoclonal immunoglobulinopathy are preferable to dysglobulinaemia and paraprotein. The clinical and immunochemical classification of monoclonal immunoglobulins, the problem of amylosis, and the relationship with plasmocytic dyscrasias and with the cryoglobulins are then discussed. Afterwards the pathogeny of these affections is briefly considered.

A new case of myeloma with antistreptolysin O activity is described. The myeloma protein is Kappa IgG. By precipitation of this myeloma IgG with anti-Kappa antiserum, the antistreptolysin O activity is completely inhibited. For the antibody activities of the myeloma protein described in the litterature, the antistreptolysin O activity is the most frequently found. With this 19th case the authors discuss the fundamental problems of the antibody activities of myeloma protein.

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.