Henry G. Kunkel

Individual Antigenic Specificity of Isolated Antibodies

Antisera produced against certain isolated human antibodies showed clear antigenic differences between these antibodies. Individual antigenic specificity was demonstrated for two anti-A antibodies, one anti-dextran, and one anti-levan antibody. Failure to produce specific antisera in other instances appeared to be correlated with a greater heterogeneity of the antibody population used as antigen.

The problem of chronic liver disease in young women

Abstract 1.1. Attention has been drawn to a group of patients suffering from a severe form of hepatic cirrhosis, the majority of whom were young women. Certain features not usually observed in patients with Laennecs cirrhosis were commonly seen. These features included arthritis, obscure febrile episodes and, occasionally, hormonal disturbances. Striking improvement followed the use of cortisone in some cases. 2.2. Laboratory investigations in the acute stages of the disease usually revealed an extremely high serum gamma globulin and an increase in the plasma cells of the liver. 3.3. The possibility that specific endocrine influences, present in young women, modify the usual course of infectious hepatitis is discussed. In most of the patients the etiology of the disease process was uncertain.

Antigenic Specificities Related to the Cold Agglutinin Activt of Gamma M Globulins

Certain antiserums prepared against isolated cold agglutinins demonstrate specificity for gamma M globulins with this activity and not for similar gamma M globulins lacking such activity. The cold agglutinin specific antigens fall into several major and minor groups. Their exact relation to the presumed antibody-combining sites remains to be determined.

Zone electrophoresis in a starch supporting medium.

Summary 1. A procedure was described for the electrophoretic separation and isolation of materials employing various types of supporting media. 2. Starch proved particularly useful because of its low adsorption of proteins and peptides in aqueous buffers. 3. A comparison was made of the electroosmotic flow in various media under similar conditions. 4. The separation of 1-4 cc of serum with isolation of the components could be carried out employing the starch system. 5. The α and β-lipoproteins of serum could be determined quantitatively by phospholipid and cholesterol analyses of the serum fractions.

LIPOPROTEIN PATTERNS OF SERUM OBTAINED BY ZONE ELECTROPHORESIS

For a number of years the lipoproteins of serum have been classified as alpha and beta types according to their electrophoretic mobility. Despite this designation very few studies of their electrophoretic properties have been reported. This is chiefly due to the fact that it is very difficult to determine exactly where the lipoproteins migrate when patterns of whole serum are obtained by the classical Tiselius method. Isolation of the lipoproteins can be achieved by chemical (1, 2) and ultracentrifugal methods (3, 4). However, even if turbidity and solubility problems in the electrophoretic separation of the isolated lipoproteins are overcome, some question remains as to whether the mobilities of these delicate complexes are the same in the isolated state as they are in whole serum. To circumvent these difficulties and to supplement the information obtained from the ultracentrifuge by Gofman, Lindgren and Elliott (3), Green, Lewis and Page (4), and Turner and associates (5) and that obtained from chemical fractionation by Lever and associates (2) and Russ, Eder and Barr (6, 7), the new technique of zone electrophoresis was applied to this problem. This method has the advantage that the electrophoretic components can be isolated directly so that lipid analyses can be carried out. The results obtained in the present study indicate that lipoprotein patterns can be obtained on whole serum and can be correlated in terms of relative electrophoretic mobility with the other proteins of serum.

The Occurrence of Single-Stranded DNA in the Serum of Patients with Systemic Lupus Erythematosus and Other Diseases

Single-stranded DNA (SDNA) occurs in high incidence and in greatest concentration in the sera of patients with systemic lupus erythematosus (SLE), where levels as high as 250 mug/ml were observed. SDNA appears to be an imunogen for anti-SDNA antibodies and forms complexes in vivo of both anti-SDNA-SDNA and anti-NDNA-SDNA types, which apparently play a role in the pathogenesis of the glomerulonephritis found in patients with SLE, SDNA is also found in high incidence but at lower levels in the sera of patients with rheumatoid arthritis. Lesser amounts of SDNA are found in several other diseases in which a low incidence of anti-SDNA antibodies is observed.

AUTOANTIBODIES AND DISEASE.

Publisher Summary The chapter discusses the autoantibodies which have been discovered in autoimmune diseases and a comparison of the reactivity against the Gm groups on human y-globulin of rheumatoid factors on the one hand with the “serum normal agglutinators” on the other. The latter often arise as a result of iso-immunization of the fetus by maternal γ-globulinRheumatoid arthritis, systemic lupus erythematosus, thyroiditi, pernicious anemia, myasthenia cravis, scleroderma and dermatomyositis, pancreatic disease, addisons disease, and ulcerative colitis are specific diseases associated with autoantibodies. Widely prevalent autoantibodies such as antinuclear antibodies, anticytoplasmic antibodies and anti-γ-globulin antibodies are also presented in this chapter. Beneficial effects in the removal of bacteria have been demonstrated for immunoconglutinin in experimental animals.

Analyses of Lymphocytes from Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus OCCURRENCE OF INTERFERING COLD-REACTIVE ANTILYMPHOCYTE ANTIBODIES

Large percentages of the lymphocytes from some patients with rheumatoid arthritis and systemic lupus erythematosus were densely covered with Ig demonstrable by immunofluorescence, which was occasionally present in the form of caps. The amount and character of the Ig staining depended largely on the procedures used in the isolation and washing of the lymphocytes. Cold-reactive antilymphocyte antibodies present in many sera wre primarily responsible for these variations. Overnight culture of the lymphocytes proved to be an efficient procedure for the removal of adsorbed antibody. Some evidence was also obtained for the presence of circulating immune complexes and exogenous rheumatoid factor molecules on the lymphocyte surface. Thus on freshly isolated cells the demonstration of surface Ig proved to an unreliable marker of bone marrow-derived (B) cells in these disease: the actual percent of B cells with intrinsic surface Ig was often markedly decreased. In patients with systemic lupus erythematosus, this reduction was in agreement with the low numbers of cells that had a receptor for aggregated IgG. The mean percentage of thymus-derived (T) cells in both diseases was slightly greater than the normal level.The concentrations of lymphocytes in joint fluids from patients with rheumatoid arthritis were often greater than levels found in blood. T cells primarily accounted for this increase. The T cells typically formed unusually dense rosettes with sheep erythrocytes. B lymphocytes were proportionally much diminished. Evidence was obtained for the existence of a major joint fluid lymphocyte population that lacked all assayed surface markers.

Hairy Cell Leukemia: Proliferation of a Cell with Phagocytic and B‐Lymphocyte Properties

Four cases of hairy cell leukemia wire studied by immunofluorescence. All hairy cells bore surface immunoglobulin. In two cases, only IgD was detected on the cell surface, whereas both IgM and IgD were present in the other two cases. After adsorbed IgG was removed by overnight culture, only one class of light chains was detected. In addition, most of the hairy cells were capable of ingesting latex particles. These findings suggest that hairy cell leukemia is caused by a monoclonal proliferation of a type of Ig‐bearing B cell with phagocytic potential.

Estimation of Alterations of Serum Gamma Globulin by a Turbidimetric Technique

Summary 1. When serum with abnormally hiqh gamma globulin concentration 1s diluted with a solution containing a certain small amount of copper or zinc sulfate, a turbid precipitate forms and the optical density of the suspension is proportional to the concentration of gamma globulin. 2. Such an estimation of increase in gamma globulin really measures the total globulin elevation in pathological sera because hyperglobulinemia is almost always due to an alteration in the gamma globulin fraction of the serum. 3. The test has proved useful for determining alterations in gamma globulin during the course of an acute illness such as infectious hepatitis. 4. It was found to be of particular value in detecting persistent liver disease following infectious hepatitis. In a group of 41 patients with cirrhosis of the liver the reaction was positive in every case.