Biomedical subjects
Publications and source records attributed to F Skvaril.
Bone marrow cells from patients with myeloma were reacted with FITC- and/or TRITC-conjugated anti-heavy chain sera and/or TRITC-conjugated anti-light chain sera. A fluorimeter with electronic setter control and short-term excitation was used for quantitative determination of FITC- and TRITC-fluorescence.
The level of antibodies specific for the two serologically distinct polysaccharides of group A and group A-variant streptococci was investigated in human sera by a modified Farr technique. Whereas there was an obvious relationship between the anti-streptolysin O titer and the level of group-A-specific antibodies, suggesting a recent streptococcal infection with group A streptococci, this correlation was not apparent for the level of group A-variant antibodies. There is evidence suggesting that children have significantly lower group A polysaccharide antibody levels than adults; this is not true of their group A-variant antibody levels. There was an apparent restriction of groups A- and A-variant-specific antibodies to the kappa light-chain type and IgG2 heavy-chain subclass. Whereas only one serum contained group A-specific antibodies also associated with IgG3 heavy chains, nine sera contained anti-group A-variant-specific antibodies with both IgG2 and IgG3 heavy chains. No anti-polysaccharide activity was detected in the IgM and IgA class of serum antibodies. Anti-group A and anti-group A-variant antibodies of human sera are restricted with respect to the number of clonotypes that are shown by isoelectric focusing. The most heterogeneous sera contained roughly ten clonotypes.
Ninety-one sera of persons above 80 years of age were screened for autoantibody activity against lipoproteins (anti-LDL 7, anti-HDL 6 positive), for rheumatoid factor activity (Latex 14, Waaler-Rose 7 positive) and for antinuclear factors (11 positive). Among the sera with autoantibody activity 29 percent showed deviations of the normal kappa/lambda ratio of immunoglobulins, as opposed to 22 percent of the sera without detected autoantibody activity. In 3 percent of the sera an M component was detected. Determination of the alpha1-acid glycoprotein, alpha1-antitrypsin, haptoglobin, haemopexin, complement component C3c and C4, IgG, IgA and IgM levels showed significant increases in alpha-, and beta-globulins as well as in IgG and IgA in sera of the aged persons as compared to a normal population between 20 and 60 years old. No significant difference was noted between the gamma-globulin concentration in sera of aged persons with or without autoantibody activity. The evaluation of the relationship between serum protein levels and alterations of the kappa/lambda ratio indicated that the alpha- and the beta-globulins were significantly raised in sera with altered kappa/lambda ratios, whereas, with the exception of M component containing sera the gamma-globulin levels seemed not significantly affected by changes in this ratio.
A marked imbalance of the two light chain types of immunoglobulins was observed in two young male adults suffering from primary hypogammaglobulinemia and intrinsic factor-deficient pernicious anemia. In one patient, the kappa/lambda light chain ratio of serum immunoglobulins was 0.01; in the other, it was approximately 6 (normal value, 1.8 +/- 0.3). This light chain imbalance was found within each of the three main immunoglobulin classes. The number of mature immunoglobulin-producing cells in the bone marrow and in the mucosa of the gastrointestinal tract was reduced. The relative frequency of kappa- and lambda-producing cells in these tissues corresponded to the kappa/lambda ratio of serum immunoglobulins. However, the number of peripheral lymphocytes with membrane-associated immunoglobulins as well as the percentage distribution of blood lymphocytes with kappa- or lambda-type immunoglobulins on the membrane were within normal limits in both cases. The results suggested a hitherto unknown defect in the maturation of B-cells leading to an abnormal ratio of kappa- and lambda-type immunoglobulin-secreting cells.
Immunoglobulin levels of individual classes and IgG subclasses and the occurrence of homogeneous immunoglobulins--paraproteins--were studied longitudinally in the sera of three patients with the Wiskott-Aldrich syndrome; Common findings in all three patients were great variations in the immunoglobulin levels, restricted heterogeneity of the immunoglobulins, the frequent appearance of transient homogeneous immunoglobulins and the presence of serum antibodies against bovine milk proteins. A partial and selective deficiency involving mainly the T immune system is postulated as an explanation for these findings.
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Plasmin-treated gamma-globulin of placental origin was tested in clinical and laboratory studies and found to be suitable for intravenous use both for prophylactic and therapeutic purposes. Plasmin treatment of gamma-globulin (IgG) results in proteolytic cleavage of 60-70% of the molecules into Fab and Fc fragments whereas 30-40% of the molecules are plasmin resistant. The antibody spectrum of plasmin-treated gamma-globulin is similar to that of standard gamma-globulin. Catabolic properties of the plasmin-resistant portion of this preparation and of standard gamma-globulin are identical. Plasmin-treated gamma-globulin has no anticomplementary activity and its intravenous administration is well tolerated even by highly sensitive immunodeficient patients.
Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man.
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Immunofluorescence studies were performed on bone marrow samples from 21 individuals with normal or slightly elevated serum IgG levels. On the average, 40.7 percent of the IgG-positive plasma cells contained molecules of the subclass IgG; 30.6 percent had intracellular IgG2; 21.7 percent, IgG3, and 7.0 percent, IgG4. These figures were compared to the relative serum IgG subclass concentrations. The principal finding was the discrepancy between the high relative number of IgG-3 producing bone marrow plasma cells and the low relative IgG3-producing bone marrow plasma cells and the low relative IgG3 serum concentration (5.5 percent of the total IgG). It was explained by the short biologic half-life of molecules of this subclass.
IgG-subclass levels were determined in the sera of 45 patients suffering from various types of immunodeficiency disease. Imbalances of IgG-subclass concentrations were found in 25 cases. IgG-4 levels were most frequently more depressed than the levels of the other subclasses. The percentage distribution of IgG-subclasses was normal in the remaining 20 sera. In a patient with autosomal recessive alymphocytic agammaglobulinemia, subclass concentrations drastically increased after bone marrow transplantion showing transient peaks of restricted heterogeneity. Normal IgG-subclass levels were reached at the end of the observation period.
The immunoperturbations in paraproteinemias are due predominantly to a disturbance of the B-cell system. The immunologic deficiency is characterized clinically by an increased susceptibility to infections and serologically by a reduction of the nonmyeloma immunoglobulins. In advances cases the capacity to produce specific antibodies is impaired. This may be attributed to a low rate of synthesis or an increased catabolism of normal immunoglobulins.
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