Immunosuppression and reconstitution with thymosin after radiation therapy.
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Biomedical subjects
Publications and source records attributed to A J Ammann.
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Precipitating antibody to cow milk's antigens (commonly bovine IgM) is found in 40-50% of selective IgA deficient patients. These precipitins may obscure the diagnosis of selective IgA deficiency by formation of anti-antiserum precipitin rings in radial immunodiffusion. Abnormal immunoregulatory function along with excess absorption of milk antigens in the absence of secretory IgA may be predisposing factors. Elimination of dietary cow's milk results in disappearance of these antibodies.
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A spontaneously occurring antibasement membrane antibody has been further characterised according to antigenic specificity, immunoglobulin class, and tissue localisation using immunofluorescent and immunoelectron microscopic techniques. The autoantibody reacted with the basement membrane of kidney tubules, Bowman's capsule, and the epithelial portion of ileum but not with the basement membrane of skin, cornea, glomerulus, or oesophagus. It also reacted with bile canaliculi, sarcolemmal sheath, and salivary duct. On electron microscopy the antibody was distributed along the basement membrane of Bowman's capsule and renal tubules. Some reactivity against collagen was observed. Antibody activity was found in both IgG and IgM fractions. In immunodeficiency disorders, the autoantibody was found only in patients with selective IgA deficiency.
Purine nucleoside phosphorylase (PNP) deficiency is associated with a severe defect in thymus-derived (T)-lymphocyte function combined with normal bone marrow-derived (B)-lymphocyte function. To investigate the role of this enzyme deficiency in the resulting immune dysfunction, we measured the levels of ribonucleoside and deoxyribonucleoside triphosphates in erythrocytes from two unrelated PNP-deficient, T-lymphocyte-deficient patients. Both PNP-deficient patients have abnormally high levels of deoxyguanosine triphosphate (deoxy-GTP) in their erythrocytes (5 and 8 nmol/ml packed erythrocytes). In contrast, normal controls and adenosine deaminase-deficient, immunodeficient patients do not have detectable amounts of deoxyGTP (<0.5 nmol/ml packed erythrocytes). We propose that deoxyguanosine, a substrate of PNP, is the potentially lymphotoxic metabolite in PNP deficiency. The mechanism of toxicity involves phosphorylation of deoxyguanosine to deoxyGTP, which acts as a potent inhibitor of mammalian ribonucleotide reductase.
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By using indirect hemagglutination, the antibody responses of normal infants and children to an octavalent pneumococcal vaccine that contained pneumococcal polysaccharide types 1, 3, 6, 7, 14, 18, 19, and 23 were evaluated. By 2 years of age, there was a significant rise in hemagglutination titers to all the polysaccharide types, except type 19. By 6 to 8 months of age, five of the eight types of pneumococcal polysaccharides tested resulted in up to 60% responders and, by 2 years, a significant number responded to all pneumococcal polysaccharide types in the vaccine. Pneumococcal polysaccharide type 3 resulted in a significant antibody response as early as 3 months of age, whereas type 19 never resulted in a significant antibody response. Except for type 3, it seemed that when the other pneumococcal polysaccharides tested produced an antibody response, the degree of resonse did not subsequently change significantly with increasing age. The relationship of antibody response to age for pneumococcal polysaccharides is similar to that found for other polysaccharide vaccines. Based on the results of our study, we would recommend immunization with pneumococcal vaccine at 6 months of age with repeat immunization at 2 years of age, especially in high-risk children.
Fifty-five patients with squamous cell carcinoma of the head and neck and esophagus were evaluated prior to irradiation and thymosin fraction 5 therapy. Immunity prior to treatment, as measured by total lymphocyte count, E and EAC rosettes, lymphocyte stimulation with phytohemagglutinin (PHA) and in mixed leukocyte culture (MLC) with allogeneic cells, delayed hypersensitivity skin tests, and quantitative serum immunoglobulins, was comparable and normal in the 40 control patients and in the 15 thymosin-treated patients. After irradiation, significant depression (P less than 0.01) was demonstrated in cellular immunity in both groups of patients with decreased T- and B-cell numbers and depressed phytohemagglutinin and MLC stimulation. Six months after irradiation, our preliminary results suggest that the thymosin-treated patients may be reversing their immunosuppression by a return of MLC function and positivity of delayed hypersensitivity skin tests. The ultimate effect of thymosin on disease control and survival remains uncertain.
To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls. Within two years after immunization we observed eight Str. pneumoniae infections in 106 age-matched unimmunized patients with sickle-cell disease, but none in the 77 immunized (P less than 0.025). We conclude that pneumococcal polysaccharides are immunogenic in hyposplenic patients and may protect against systemic Str. pneumoniae infection.
Cultured skin fibroblasts from a patient with T-cell immune deficiency and an absence of purine nucleoside phosphorylase activity in red cells were assayed for their capacity to metabolize inosine and guanosine. The cultured fibroblasts were lacking activity of nucleoside phosphorylase and, compared to normal fibroblasts, could incorporate only 2% and 4% of 14C-inosine and 3H-guanosine, respectively, into acid precipitable material. Autoradiography visually confirmed the failure of the NP deficient cell line to incorporate the nucleosides into nuclear material. The physiological mechanism by which the deficiency of purine nucleoside phosphorylase causes T-cell dysfunction remains unclear.
A method for quantitating peripheral blood B cells is described which utilizes anti-heavy chain specific antibody attached to polyacrylamide beads. The method has the advantages of ease of performance, of utilizing reagents which are commercially available and routine phase microscopy. In addition, the reagents are stable for prolonged periods of time and only small amounts are required. Utilizing this assay, the following percentages of B cells have been found in normals: IgG 6.3 +/- 0.6; IgM 4.3 +/- 0.5; IgA 4.0 +/- 0.5. The polyacrylamide beads may be phatocytized allowed recognition of certain phagocytic mononuclear cells.
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