Biologic and clinical significance of cryoglobulins. A report of 86 cases.

Pathogenesis of lipoid nephrosis : a disorder of T-cell function

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

Glucocorticosteroid Therapy: Mechanisms of Action and Clinical Considerations

The γ1A present in saliva and colostrum exists largely in the form of higher polymers, the major component of which has a sedimentation coefficient of 11S. The 11S γ1A in these fluids differs from the polymers found in normal and myeloma sera both immunologically and by the fact that their sedimentation coefficients are unaffected by disulfide bond reduction in the absence of urea. However, like other γ-globulins the 11S γ1A molecules consist of multiple polypeptide chains linked by disulfide bonds. Local synthesis of γ1A in the salivary gland has been shown by fluorescent and autoradiographic studies, although the fraction of the total salivary γ1A which is derived from local production is uncertain. No evidence of transport of intravenously administered I131-labeled 7S γ1A from serum to saliva was obtained. Immunological specificity has been demonstrated in the salivary and colostral γ1A. Whether that portion of the γ1A which is immunologically specific is a piece incorporated during the local synthesis of γ1A in the gland or is added by the epithelial cell in the process of transport remains to be determined. Antibody activity (isohemagglutinins) have been demonstrated in saliva and colostrum and have been shown to be of the γ1A-type. In both of these fluids activity is associated primarily with γ1A-polymers of 11S and 18S sizes. There appears to be an immunological system which is characteristic of certain external secretions. Its properties including the local production of a distinctive type of antibody separate it from the "systemic" system responsible for the production of circulating antibody. This system may play a significant role in the body's defense mechanisms against allergens and microorganisms.

/pdf/characteristics-of-an-immune-system-common-to-certain-3skzszb2t2.pdf

Characteristics of an immune system common to certain external secretions

The microdroplet lymphocyte cytotoxicity test is universally accepted as the standard test for HLA antigen determination. An update of the technical details of the test is given, based on the authors’ testing 160,000 persons. Methods for quality control of the test as well as reproducibility data are provided. International standardization of the specificities has been accomplished by seven international workshops and a continuous cell exchange involving testing of 108 cells since 1974 by as many as 180 laboratories. The test has recently become applicable to the detection of HLA-D determinants, previously thought to be detectable only by lymphocyte-determined (LD) tests. Purified peripheral blood lymphocytes are reacted with antisera from which HLA-A, -B, and -C antibodies have been removed. B lymphocytes were found to be smaller than T lymphocytes by Coulter counter sizing. The purity of cell suspensions enriched for B lymphocytes can be individually monitored, as shown by the reactions produced by 126 test samples. HLA-D antigens have a linkage disequilibrium with certain HLA-A and -B specificities as demonstrated by population and family studies. Haplotypes found in 34 parents of 18 families demonstrate the new haplotypes, which now consist of four antigens per haplotype. Studies of HLA-D frequencies in Caucasians, Negroes, and Orientals show a distinctive distribution in the races. B lymphocytes also appear to have an autoantigen against which autoantibodies are readily produced. The autoantibodies are more active against B than T lymphocytes and act most effectively at 5 C. Although they appear in many diseases, most notably in systemic lupus erythematosus, they also occur in 10% of normal males and females. In patients awaiting kidney transplants, antibodies against B lymphocytes are often found. Patients with cold B-cell antibodies (autoantibodies) were shown to have higher transplant survival rates than those with warm B-cell antibodies (allogeneic). Thus, in performing crossmatch tests it is now necessary to distinguish antibodies against T and B lymphocytes and those that react in cold and in warm conditions.

Microdroplet testing for HLA-A, -B, -C, and -D antigens. The Phillip Levine Award Lecture.

Lymphocytotoxic antibodies were found in 56 of 64 serum specimens from patients with systemic lupus erythematosus and 30 of 53 patients with rheumatoid arthritis. These cytotoxic antibodies characteristically reacted with a temperature optimum of 15°C as was found earlier with serums from patients with infectious mononucleosis, rubella and rubeola. The lymphotoxin found in systemic lupus was cytotoxic to autologous lymphocytes in 24 of 32 specimens tested. No correlation was found to the antibodies detected by radioactive labeled deoxyribonucleic acid (DNA) immunoelectrophoresis, antibodies against single-strand DNA and DNA. However, a definite association with antinuclear-factor activity and a weak association with latex-fixation tests were found. Association of specificity was tested against 18 different HL-A specificities, and antibodies against HL-A11, Te54, Te56 and Te59 were frequently observed.

https://www.nejm.org/doi/pdf/10.1056/NEJM197010012831403?listPDF=true

Cytotoxins in disease. Autocytotoxins in lupus.

Normal subjects given 60 mg of prednisone orally at 8:00 a.m. developed a transient lymphopenia at 2:00 p.m. To define the populations of lymphocytes affected the number and type of lymphocytes in the peripheral blood were assayed. "Late" and "early" spontaneous sheep red blood cell rosettes were used as markers for thymus-derived (T) lymphocytes and one of its subpopulations, respectively. Receptors for aggregated gammaglobulin and complement identified bursal-equivalent or bone marrow-derived (B) lymphocytes and one of its subpopulations, respectively. 6 h after administration of 60 mg of prednisone, the blood samples showed a decrease in proportion of T cells from 69.2 +/- 2.1% to 55.9 +/- 2.8% (average +/- SE) and an increase in B-cell proportion from 21.3 +/- 2.0% to 44.8 +/- 4.1%. The changes of "early" rosettes and complement receptor lymphocytes also paralleled these. In all cases the absolute numbers of T cells and of B cells were decreased by prednisone. The density gradient distribution of the lymphocytes did not change after prednisone. These data indicate that both T and B lymphocytes are affected by the prednisone but that the T cell lymphopenia was more pronounced. The lymphopenia might reflect either sequestration in the marrow and/or transient arrest of recirculation.

/pdf/human-lymphocyte-subpopulations-effect-of-corticosteroids-2mt0qfoe03.pdf

Human lymphocyte subpopulations. Effect of corticosteroids.

A retrospective analysis of the course of systemic lupus erythematosus in pregnant patients hospitalized at UCLA during a 15-year period provided important prognostic information. Women wi...

Systemic Lupus Erythematosus in Pregnancy

Clinical and immunologic features in ten patients with cytomegalovirus-induced postperfusion syndrome were studied. Fever, hepatosplenomegaly, and lymphocytosis were the most frequent clin...

Immunologic Abnormalities Induced by Postperfusion Cytomegalovirus Infection

Serum globulins that precipitate on cooling and redissolve on warming may occur in a variety of clinically dissimilar disorders. In some cases their presence may be a manifestation of "imm...

Eugene V. Barnett

Papers

Cytotoxins in disease. Autocytotoxins in lupus.

Human lymphocyte subpopulations. Effect of corticosteroids.

Systemic Lupus Erythematosus in Pregnancy

Immunologic Abnormalities Induced by Postperfusion Cytomegalovirus Infection

Cryoglobulinemia and Disease