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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↗

[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↗

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↗

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↗

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↗

[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↗