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Relationship between homogeneous IgG fractions and measles virus antibody activities in subacute sclerosing panencephalitis brain.

Cellulose acetate and agarose gel electrophoresis of pH 7.4 brain extracts from three patients with subacute sclerosing panencephalitis (SSPE) revealed two to three homogeneous bands in the gamma-globulin region. The IgG concentration in the brain extracts ranged from 6 to 8.5% of the total protein. The IgG was isolated by passing each brain extract twice through gel filtration on Sephadex G-200 column. The Sephadex-isolated IgG preparations, at a concentration of 1 mg/ml, had hemagglutination inhibition (HI) titers ranging from 512 to 800, complement fixation (CF) titers of 64 to 100, and neutralizing titers of 400 to 1024 when tested against envelope, nucleocapsids, and while measles virus, respectively. These IgG preparations were further separated into several fractions by isoelectric focusing (IEF) technique and the reactivities of these eluted fractions were examined against differnt specific measles virus components and against whole virus. The results showed that both slow and fast moving homogeneous IgG had high HI and neutralizing titers. However, CF antibodies were present only in specific IEF-eluted fractions and their profiles differed somewhat from one brain to another. The IgG fractions reacted with both kappa-and gamma-chain antisera, but the reactivity varied from one brain to another. When the polyacrylamide gel electrophoretic (PAGE) patterns of heavy (H) and light (L) chains of SSPE IgG were compared to those of IgG from controls, the H chain patterns of both groups were identical whereas the SSPE brain IgG demonstrated two distinct bands in L chain as compared to a single diffuse band observed in controls. These latter results, in addition to homogeneous bands and selective CF antibody activity in IEF eluted IgG fractions from SSPE brain, fulfill some of the criteria of monoclonality.

Antibodies, Viral↗

[Monoclonal gammapathy of a familial type. Discovery of myeloma in the sister of a patient suffering from Waldenstrom's macroglobulinemia].

The relatives of a 82 years old female patients with a Waldenstrom Macroglobulinemia were submitted to clinical and hematological investigations. A diclonal gammapathy (IgG kappa and IgG lambda) was found in the sister's serum and was related to a myeloma. A noticiable Bence Jones Proteinuria (light chain of lambda type) was equally found in serum and urines of the propositus brother but without any clinical or hematological evidence of myeloma. The examination of two other sisters of these patients does not reveal any immunological of hematological disorder. This new observation underlines the interest of a systematical investigation in the siblings of the patients with monoclonal gammapathies.

Aged↗

[Platelet abnormalities in dysproteinemias (author's transl)].

Hémorrhagic manifestations are relatively common in dysproteinemias (7 à 15% in myeloma, 36% in macroglobulinemia) but they are not often related to a qualitative platelet defect. In the present work we have studied the influence of some monoclonal immunoglobulins on the function of isolated normal platelets. The results show that platelet aggregations to collagen and ADP are impaired in presence of high concentration of paraproteins (about 50 gm/l). The molecular size of the protein is also important. This is in agreement with most studies and support the hypothesis that paraproteins interfere with platelet activity.

Blood Platelet Disorders↗

The value of cerebrospinal fluid immunoglobulin analysis in clincial neurology.

The IgG index (formula: see text) corrects for the influence of serum protein abnormalities as well as a bloodbrain barrier damage and is, therefore, a better measure for the presence of an IgG elevation in CSF due to IgG synthesis, when compared with other IgG quotients commonly used. Agar gel electrophoresis of CSF for demonstration of oligoclonal IgG is probably superior to the determination of the IgG index when a diagnosis of MS is suspected. Determination of kappa and lambda light chain antigenic determinants in CSF, and calculation of the kappa/lambda ratio may also be used to demonstrate the occurrence of oligoclonal CSF immunoglobulins. An abnormal ratio can, however, be demonstrated only in 50% of MS patients and has, therefore, at present no place as a routine diagnostic method when MS is suspected.

Humans↗

[Production of rabbit precipitating antisera to subclasses of human IgG].

Precipitating antisera to human subclasses IgG were obtained by immunization of rabbits by whole molecules IgG2, IgG3, IgG4 and gamma 1-chains derived from IgG1H (Pr). Analysis of the antisera obtained demonstrated that rabbits produced specific antibodies to the antigenic subclass determinants IgG3 well, to IgG2, IgG4--much worse, and failed to produce specific antibodies to subclass IgG1 (in immunization with whole molecules of this protein). Antisera contained antibodies to the antigenic determinants common of IgG, and antibodies to light chains which were removed by immunosorption, for which purpose a sorbent on the basis of BrCN sepharose conjugated with IgG of the three other subclasses and Fab-fragment was used.

Animals↗

IgD myeloma protein with "unreactive" light chain determinants.

Serum from a patient with multiple myeloma showed a monoclonal protein, classified by immunoelectrophoresis as IgD. Immunofixation electrophoresis and immunoelectrophoresis failed to demonstrate a precipitation reaction between the paraprotein and antisera to immunoglobulin light chains. The light chains of the monoclonal protein, immunologically inaccessible in the intact molecule, reacted with anti-lambda chain antisera only after reduction and alkylation of the paraprotein. Moreover, interpretation of the immunoelectrophoretic patterns was hampered by the presence in patient's serum of free lambda chains having about the same mobility as that of the paraprotein.

Aged↗

[Contribution of new methods of quantitative cytology and immunology to the understanding of lymphoproliferative syndromes].

Seventy one patients with a lymphoid hemopathy, three with agammaglobulinemia and six normal controls were investigated with regard to their blood lymphocyte membrane-associated light chains. Detection and quantitation of antigenic determinants were performed by means of peroxidase-labeled antibodies. Compared to normal controls, values found in chronic lymphocytic leukemia (CLL) were very low (tenfold decrease). The number of antigenic determinants on lymphoid cells from patients with blast crises supervening in CLL, prolymphocytic leukemia, Waldenstrom's macroglobulinemia and Burkitt cell acute leukemia were significantly higher than those seen in patients with CLL. The data obtained in this investigation through quantitative immunocytology constitutes a new parameter for the classification of lymphoid hemopathies and for an approach to their pathogenesis, in particular if the quantity of membrane immunoglobulin correlates with the stage of cell maturation.

Antibodies↗

[Participation of rat immunoglobulin light chains of the kappa and lambda type in formation of antibodies to the polysaccharide of group A streptococcus].

The role of light kappa and lambda chains and also allelic variants of kappa chains of rat immunoglobins in the formation of antibodies to beta-N-acetyl-glucosamine polysaccharides of streptococcus group A of inbred rat strains MSU, WAG, August and hybrids of the first generation (MUS X WAG)F1 and (MSU X August)F1 was studied. From individual sera of immune rats fractions of specific antibodies to beta-N-acetyl-glucosamine were isolated. These antibodies differ in their affinity to antigenes. The retio of molecules with kappa and lambda light chain types was determined for the fraction of specific antibodies. The ratio of molecules kappa and lambda depends on the affinity of antibodies to beta-N-acetyl-glucosamine and on the genotype of the animals studied. Data obtained allow to conclude that differences in the functional activity of lambda chains between strains WAG and August, on one hand, and strain MSU, on the other, do exist. Functional differences releaved between these rat strains were confirmed by analyzing corresponding antibody fractions to beta-N-acetylglucosamine in F1 hybrids. Differences between allelic variants of kappa chains in the formation of antibodies to beta-N-acetylglucosamine of polysaccharides were not found.

Acetylglucosamine↗

Cryoglobulinemia and amyloidosis associated with intestinal lymphoma.

A case of lymphocytic lymphoma of the small intestine was associated with cryoglobulinemia and amyloidosis. The neoplastic lymphoid cell demonstrated surface IgG membrane markers by immunofluorescence and immunoelectron microscopy. The cryoglobulins were characterized as monoclonal IgG3 proteins with lambda light chains. Amyloidosis of the small intestine and regional lymph nodes was found in association with lymphatic infiltration of these organs, suggesting the production of amyloid in situ.

Aged↗

Immunohistochemical characterization of Burkitt's lymphoma.

Cytoplasmic immunoglobulins and muramidase (lysozyme) were demonstrated in formalin-fixed tissues by an immunoperoxidase procedure in 3 cases of Burkitt's lymphoma. The Burkitt cells were strongly positive with the full panel of monospecific antisera against human immunoglobulin components (kappa and lambda light chains, gamma, alpha and micron heavy chains). The 'starry-sky' macrophages were weakly positive with antimuramidase antiserum and strongly positive with the antisera against immunoglobulins, thus demonstrating their phagocytic and histiocytic nature. The reasons for the polyclonal increase in immunoglobulins are discussed.

B-Lymphocytes↗

Normal values for free light chains in serum different age groups.

The concentration of free light chains from the immunoglobulins was measured in twelve paired sera from mothers and newborns and from 149 sera from normal individuals in various age groups. Variations in concentration during life are correlated to the variations in the concentration of 'regular' immunoglobulins. A concentration of light chains in cord blood of 35% of mean normal adult level (MNA) together with a rapid passage of light chains across the placenta is interpreted as indicating catabolization of maternal light chains in the fetus. This is further supported by the finding of a lower concentration of light chains in maternal serum than in normal adult serum. The investigation shows that the concentration of light chains falls rapidly from 35 to 24% of MNA during the first few days of life. From the first week of life the concentration of light chains increases and low normal adult values are attained by one year of age. Except for difference in concentration, the elution pattern for light chains from Sephadex G-100 columns was similar for normal, adult and cord blood. The relationship between kappa and lambda chains--the K/L ratio--is 1.2 for normal and maternal serum and 1.0 for cord serum.

Adolescent↗

[Determination of the subclasses of monoclonal human immunoglobulins G and of the light chain type with the aid of specific antisera].

Sera of 86 patients suffering from G-myeloma were studied for the purpose of determination of subclasses of monoclone IgG. Investigations were carried out by means of antisera to subclasses IgG by the double diffusion method in gel after Ouchterlony. The following distribution of myeloma Ig was revealed: G1--70%, G2--17%, G3--11%,and G4--2%. In typing of the light igG chains by the method of immunoelectrophoresis, using antisera to the light chains of immunoglobulins of the chi and lambda type it was found that IgG1 chi was encountered more frequently than IgG1 lambda (3:1 ratio). The amount of the sera with the IgG2, IgG3, and IgG4 was insufficient for the reliable conclusion of their distribution by the type of light chains.

Humans↗

Monoclonal plasma cell population in the uterus.

The case of a 28-year-old female patient is presented. Heavy infiltration with plasma cells of uterine tissue removed by surgical currettage following an aborted pregnancy was detected by cytological and histological examination. Subsequent immunohistochemical studies revealed the monoclonal nature of these cells: intracellular immunoglobulin contained gamma- and lambda-chains exclusively. Since careful clinical examination produced no evidence in favor of multiple myeloma, these findings were tentatively interpreted to be compatible with the diagnosis of solitary plasmocytoma of the uterus.

Abortion, Habitual↗

[Rule of antibody structure. Primary structure of a human monoclonal IgAl-immunoglobulin (myeloma protein Tro). VI. Amino acid sequence of the L-chain, lambda-type, subgroup II].

The primary structure of the L-chain of an IgA1-immunoglobulin (Myeloma protein Tro) has been determined by means of cleavage with trypsin and, if necessary, with alpha-chymotrypsin. The tryptic peptides of the variable part were characterized by amino acid analysis, Dansyl-Edman degradation and cleavage with carboxypeptidase; the peptides of the constant part were identified by amino acid analyses and determination of its N- and C-terminal residues. The sequence of the remaining amino acids and the arrangement of the peptides were established in homology to known structures. The protein comprises 216 amino acids. The homology of the variable part clearly characterizes it as belonging to subgroup II of lambda-chains. In positions 27a, b and c, there are the subgroup-specific additional residues and in position 96 is the characteristic deletion. The constant part of the chain is Kern- and Oz- which indicates that it has serine in position 154 and arginine in position 191.

Amino Acid Sequence↗

Morphological classification of malignant lymphomas: ultrastructural, cytochemical and immunological results.

Except for tumors clearly producing immunoglobulin (e.g. plasma-cytoma), the different classes of malignant lymphomas do not correlate with a constant surface immunoglobulin pattern. Beside a prevailing IgM-surface type in a high number of different lymphoma classes even T-like or O-cells occur in most tumor types provided they are studied in a sufficient number. The possibility of dedifferentiation of immunologic cell qualities has to be envisaged. In this context intracellular lambda-chain crystals occurring in chronic lymphocytic leukaemia may provide a morphological hallmark of anaplastic deterioration of immunoglobulin synthesis. - The ambiguous significance of PAS-positive inclusions and virus-like microtubular complexes in lymphoma cells is discussed. - In conclusion the recent discovery of hairy cell leukaemia provides a good example of the value of nomenclatures based on empiricism rather than on short-lived theories.

B-Lymphocytes↗

Hairy cell leukemia: functional, immunologic, kinetic, and ultrastructural characterization.

A diagnosis of hairy cell leukemia was made by optic microscopy, phase-contrast microscopy, electron microscopy, scanning microscopy, and histochemistry of the abnormal blood cells. In vivo these cells were found to have a half-time in the blood of approximately 150 hr. In vitro they had the capacity to adhere firmly to plastic, making it possible to obtain a pure population of hairy cells. Neither T-rosette formation nor phytohemagglutinin (PHA) transformation could be demonstrated in these cells. On the other hand, the presence of immunoglobulins on the surface of the hairy cells (HC) by immunofluorescence, and the synthesis and secretion by these cells of IgM type lambda-chains shown by radioimmunodiffusion, were in favor of their B-type lymphocyte origin. Similarities to chronic lymphocytic leukemia were apparent.

Bone Marrow↗