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PubMed1976

Comparative studies on monotypic IgMlamba and IgGkappa from an individual patient. II. Amino-terminal sequence analyses.

Amino terminal sequence analyses were performed on the H and L chains of the idiotypically related IgMlambda and IgGkappa paraproteins isolated from the sera of a patient, Br. The N-terminal 41 residues of the Br k-chain belonged to the Vkiii subgroup, and L chains derived from BrIgMlambda revealed a blocked N-terminus characteristics of lambda-chains. Comparative sequence analysis of the Br mu- and gamma-chains indicated that, although both possessed an unblocked N-terminal glutamic acid, the respective VH regions belonged to seperate subgroups. The N-terminal 27 residues of the Br mu-chain reflected a typical VHiii subgroup sequence. The Br gamma-chain sequence demonstrated a VHI pattern with an unblocked N-terminus. These structural data stand in contrast to previously reported serologic evidence, which indicated that the BrIgMlambda and BrIgGkappa proteins possessed highly similar Vh-associated idiotypic determinants. Final interpretation of these findings of similar Vh idiotypic determinants expressed by H chains belonging to seperate Vh subgroups must await complete sequence analysis of hypervariable segments of the Br gamma- and mu-chains.

Amino Acid Sequence↗
PubMed1976

IgA and IgM cytoplastic inclusions in a series of cases of chronic lymphocytic leukaemia.

Seventy-two cases of typical chronic lymphocytic leukaemia were screened by electron microscopy for the presence of intracytoplasmic immunoglobulin crystals. Immunoglobulin inclusions were found in four cases. Immunofluorescent studies showed that the inclusions contained IgA in two cases and IgM in the other two patients. Lambda light chain specificity was demonstrated in all four cases. The ultrastructure of the inclusions was identical in each patient except that in one of the IgA cases the inclusions were found in the perinuclear cistern in addition to the more usual location within cisternae of rough endoplasmic reticulum. Surface immunofluorescence showed mu heavy chains in the two cases displaying IgM crystal formation, but in the two IgA patients, no alpha heavy chains were demonstrable at the cell surface. The possible significance of these findings is discussed in relation to the existing literature.

Cytoplasm↗
PubMed1976

[M-component of serum formed by lambda-type Bence-Jones protein].

M-component in the serum composed of free light chains occurs rarely as evidenced by literature. In the investigations of the authors it was demonstrated that three M components obtained from patients with plasmocytoma were composed of free light chains type lambda. High concentration of low-molecular protein in serum was due, probably, to coexistent impairment of renal filtration. It is worth stressing that M component was a lambda-type chain which may explain the pathogenesis of renal failure caused by amyloidosis.

Amyloidosis↗
PubMed1976

Kappa and lambda light chain disease: survival rates and clinical manifestations.

Ninety-seven patients with light chain disease (LCD) were studied. The median survival from diagnosis was 30 mo for 52 patients with kappa-LCD and 10 mo for 45 patients with lambda-LCD (p less than 0.0007). A lower proportion of kappa-LCD patients (15.7%) than lambda-LCD patients (42.2%) died within the first 6 mo after diagnosis. The survival of the remaining patients with kappa-LCD was still much longer than of those with lambda-LCD (p = 0.022). The shorter survival of lambda-LCD patients could not be ascribed to an increased incidence of recognized manifestations indicating a poor prognosis (e.g., anemia, hypercalcemia, azotemia, low albumin, the extent of osteolytic lesions, or proteinuria), the incidence of amyloidosis, the clinical stage of the disease at diagnosis, or the response to treatment, and remains unexplained. A comparison of the clinical manifestations of LCD with those of other myelomas revealed some differences. LCD patients were slightly younger than IgA and IgG patients but older than IgD patients. A 1:1 ratio of males to females was similar to the ratios in IgA and IgG myeloma, but differed from the 3:1 ratio reported for IgD myeloma. Plasma-cell leukemia developed in 7/97 LCD patients, an incidence that was higher than has been reported in other myelomas. The initial BUN was more than or equal to 30 mg/100 ml in 54 of 95 LCD patients, an incidence that was higher than has been reported for IgA and IgG myeloma, but lower than the incidence in IgD myeloma. The incidence of amyloidosis in LCD (23 of 97 patients) was similar to that reported for IgA and IgG myeloma, but less than the incidence in IgD myeloma.

Adult↗
PubMed1975

A case of IgD-lambda myeloma.

A case of IgD myeloma is presented. The severe damage of both kidneys resulted in uraemia, and death. Fluorescein angiography failed to reveal a typical paraproteinaemic fundus. The elevated serum IgD level decreased form 1000 mg to 400 mg per 100 ml during cytostatic therapy. The effect of the antineoplastic drugs on the plasmocytes was demonstrated by microphotograms. The caryograms revealed multiple changes.

Aged↗
PubMed1975

Distribution of heavy chain classes and light chain types in 757 cases of monoclonal gammapathies.

The distribution in heavy chain classes and light chain types of M components were studied in 757 cases of monoclonal gammapathies. These gammapathies were classified according to clinical and hematological data in 439 myeloma (MM), 165 Waldenström's macroglobulinemia (WM) and 152 monoclonal gammapathies occurring in other conditions. The IgG/IgA ratio differs in myeloma and in non-myelomatous gammapathies (64% IgG versus 33% IgA in myeloma and 95% IgG versus 5% in absence of myeloma). Presence of free light chains in patient's urines (Bence Jones proteinuria) was detected in about 72% of cases of MM, 48% of WM and only in 9% in others gammapathies. Concerning the sex of patients, an equal repartition between males and females is observed in MM, whereas males predominate in WM. The age distribution of the patients shows that 74% of myeloma and 79% of WM were above sixty. In addition to the 757 cases under study, 10 sera with two M Components were characterized.

Adult↗
PubMed1976

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↗
PubMed1976

[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↗
PubMed1976

[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↗
PubMedDate not supplied

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↗
PubMed1979

[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↗