Correlation of euglobulin immunoglobulin G levels with erythema nodosum leprosum in lepromatous leprosy.
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Biomedical subjects
Publications and source records attributed to M Reichlin.
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Skin nuclear speckled IgG deposition was noted in seven patients. The patients' clinical courses satisfied at least four of the preliminary criteria of the American Rheumatism Association for the diagnosis of systemic lupus erthematosus (SLE). Examination of approximately 700 additional biopsies from patiets with SLE, connective tissue and various skin diseases as well as normal individuals, failed to demonstrate similar nuclear immunoglobulin deposition. Sera from these seven patients had higher titre, complement fixing anti-nuclear antibodies (ANA) of IgG class which produced a speckled nuclear fluorescent pattern. In addition, the sera of all seven patients demonstrated by gel double diffusion precipitating antibodies against nuclear ribonucleoprotein (RNP) or Sm antigens.
The ferritin concentration of duodenum, liver, and spleen and the incorporation of L-leucine-3H into immunoprecipitated duodenal and liver ferritin was measured in genotypically normal (+/Y) mice and mice with sex-linked anemia (sla/Y), an X-linked recessive trait determined by a defect in intestinal iron absorption. Liver and splenic ferritin concentration was lower in sla/Y animals than in +/Y animals. Parenteral iron administration produced an increase in the duodenal, liver, and splenic ferritin concentration in both sla/Y and +/Y animals that was most striking in the case of the liver. Duodenal ferritin synthesis, both in vivo and in vitro, was increased in iron-deficient sla/Y animals and decreased in iron-deficient +/Y animals. In contrast, liver ferritin synthesis was decreased in both sla/Y and +/Y iron-deficient animals. In sla/Y animals fed an iron-deficient diet, duodenal ferritin synthesis decreased to near normal levels. These results indicating a high level of duodenal ferritin synthesis in standard-fed mice with sex-linked anemia suggest that the primary genetic defect is more likely a disorder of intramucosal iron transport than a primary disturbance of ferritin metabolism.
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Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immuno-reactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that crossreacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous.
The antigenic properties of the hemoglobins of two species of rainbow trout, Salmo irideus and Salmo gairdneri, have been compared. Each of these species possess two different classes of hemoglobins, the members of the first of which have no Bohr effect while those of the second exhibit a pronounced pH dependence of their ligand affinities. The hemoglobins from these two species are antigenically indistinguishable. However, between the two classes of hemoglobins there is almost no immunological cross-reactivity.
A specific binding test was used to detect immune complexes containing antigens of Mycobacterium lepraemurium in the serum and tissues of infected mice. Complexes were precipitated by antiserum against immunoglogulin, free antigen removed by washing and the presence of bound antigen demonstrated by measurement of uptake of radioactively labelled specific antibody by the precipitate. Tests were done both with 125I-labelled FAB prepared from an immune from rabbit antiserum against M. Lepraemurium and with 125I-labelled IgG precipitate. Out of seventy-nine serum samples taken monthly up to the 5th month after infection, only there were positive (one at 2 months and two at 3 months). Kidneys taken from infected mice were also examined for immune complexes. Although deposits of IgM and sometimes of IgG were observed by immunoflourescence in glomeruli of normal mice, deposits of IgG were more frequent later on in infected mice. Nevertheless, binding tests done on acid eluates were positive in only one out of fifty-three infected mice.
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Previously, we had reported the isolation of an antibody population (termed antiVal antibody) specific for the site of difference between human hemoglobin S(HbS)(beta-6Val) and hemoglobin A-1(BbA)(beta-6 glu). This population has a stoichiometry of reaction of unity in combining with HbS (alpha-beta-dimer) and shows no reaction with HbA. The combination of antiVal Fab fragments with HbS was found to be kinetically homogeneous and had a second order rate constant of 0.58 times 10-6M-1 sec-1 at 20 degrees C. In this report we have studied other properties of the antiVal population. These antibodies are restricted to only one of the two heavy chain subclasses of goat IgG. Electrophoresis experiments indicated that the antiVal population is much less polydisperse than the total antiHbS response. A method was developed to measure the dissociation kinetics of antiVal-HbS complexes. This dissociation was also found to be kinetically homogeneous and could be described by a single first order rate constant of 2.67 times 10-5 sec-1 at 20 degrees C. With homogeneous association and dissociation rate constants, an affinity constant of 2.1 times 10-10M-1 at 20 degrees C was calculated. It appears, then, that this population of antibodies, which are directed toward a single antigenic determinant on a globular protein, exhibit limited structural heterogeneity associated with great functional homogeneity.
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