Enhanced response of serum IgG class of anti-PGL-I antibodies in leprosy patients during onset and following clinical remission of type 1 and type 2 reactions.
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Adult↗
Biomedical subjects
A K Chakrabarty
Publications and source records attributed to A K Chakrabarty.
Modulation of Fc and C3b receptor activity of mouse peritoneal macrophages elicited by preformed immune complexes.
A study was undertaken to reveal the role of Fc and C3b receptor of mouse peritoneal macrophages (MPM) in the uptake of radiolabelled immune complexes. Large latticed preformed complexes consisting of human serum albumin (HSA)-anti HSA at equivalence (IC-Eq) and with antibody excess (IC-Ab) were observed to be avidly taken up by resident macrophages unlike small size complexes with antigen excess (IC-Ag). Macrophages elicited by thioglycollate (Tg) showed higher IC-binding capacity while IC-elicited MPM showed reduction in the same when compared to the resident cells. However, complement coated complexes were significantly taken up by these IC-elicited macrophages. Uptake studies were further extended to determine the expression of Fc and C3b receptor activity in MPM when elicited with preformed IC. Tg-elicited MPM were observed to bind greater number of IgG-coated erythrocytes (E-IgG) than resident MPM whereas IC-elicited MPM bound E-IgG poorly. When Fc receptors were blocked by in vitro IC treatment, poor binding of complement coated E-IgG [E(IgG)C] was recorded in resident MPM. The present complement medicated rosetting data tends to show enhanced expression of C3b receptors on IC-elicited macrophages.
Animals↗
Biochemical studies on stimulation of mouse peritoneal macrophages by interaction with preformed immune complexes.
Mouse peritoneal macrophages (MPM) were observed to be stimulated by both in vivo and in vitro interactions with preformed HSA-anti HSA immune complexes (IC) having different antigen-antibody ratios. This was indicated by cellular alterations in morphology, increase in cellular protein and lysosomal enzyme contents and a marked fall in 5' nucleotidase level. Analysis of cellular proteins of IC-elicited cells by SDS-polyacrylamide gel electrophoresis showed accumulation of 80, 47, 33, 28, 18 and 14 kDa proteins. Insoluble immune complexes at equivalence (IC-Eq) was found to be more effective in the stimulation process as compared to the soluble antigen excess complexes (IC-Ag). These IC-elicited cells secreted lesser amounts of lysosomal hydrolases when explanted in culture medium as compared to resting cells, whereas in vitro stimulation of resident MPM with IC resulted in enhanced lysosomal hydrolase release. IC-induced lysosomal secretion was time and dose dependent and varied with the nature of the complexes. Complement coated immune complexes (IC-CC) induced maximum enzyme secretion followed by IC-Eq and IC-Ag.
Animals↗
Delayed clearance of circulating immune complexes in mice following administration of antileprosy drugs.
In this report we describe an animal experiment which showed delayed clearance of preformed 125I-HSA-anti-HSA immune complexes (with five times excess HSA) from the circulation of mice treated with antileprosy drugs (dapsone, clofazimine, and rifampin--multidrug therapy for 7 days) in comparison with normal (untreated) mice. The results also showed delayed retention of the preformed immune complexes in the spleen and kidneys of the antileprosy-drug-treated animals. The exact mechanism of the delayed handling of preformed immune complexes in mice fed antileprosy drugs could not be ascertained. However, in light of the anticomplementary effects of clofazimine and dapsone, as reported earlier, and in light of the large accumulation of clofazimine and rifampin in macrophages, it has been postulated that in the drug-fed animals either the immune complexes could not be phagocytosed by macrophages, through the avenue of their C3b receptors, or the immune complexes could not be downgraded easily within the macrophages overloaded with clofazimine and rifampin. These results might have clinical significance and might throw some light on the prolonged persistence of circulating immune complexes in the vascular bed of lepromatous patients even after clinical remission of erythema nodosum leprosum.
Animals↗
Nutritional status of children of urban leprosy patients staying at preventoria based on biochemical parameters.
Measurements of nutritionally relevant biochemical and endocrine variables were made on 60 apparently healthy children (group A) whose parents suffered from leprosy and who had been separated at the age of 4 years and brought up in preventoria. Most of the measurements were also made on a comparison group of healthy children from the same poor socio-economic class (group B). In both groups the serum concentrations of cholesterol and triglycerides were well below those found in Western populations. Almost all the children in both groups were anaemic, but serum iron and ferritin levels were satisfactory. Folate and vitamin B12 levels were measured in group A only and were low in a significant proportion. Deficiency of these water-soluble vitamins may be a cause of the anaemia. Low albumin levels were found in 40% of group A children, compared with 2% in group B. The concentrations of calcium and magnesium were lower and that of phosphate higher in group A than in B. In both groups one-third of the children had low levels of serum zinc. Fifteen per cent of group A children had biochemical evidence of vitamin A deficiency, but none were deficient in vitamin E. Levels of total T3 and total T4 were below the lower limit of normal in a substantial proportion of children in both groups. Concentrations of parathyroid hormone were increased in parallel with the low values for serum calcium. Radiological studies of ossification centres in 57 group A children showed delayed maturation in 11 cases. The relevance of these findings to previous studies of the children of lepers in India is discussed.
Adolescent↗
Effects of preformed immune complexes on liver enzymes & their serum clearance in mice.
Two different performed HSA-anti-HSA immune aggregates, insoluble complex at equivalence (IC-E) and soluble complex with 5 times antigen excess (IC-S)-were administered iv in experimental mice to study their interaction with liver cells. Both complexes produced no appreciable change in the levels of liver enzymes like acid phosphatase, cathepsin D and gamma-glutamyl transferase. However, marked reduction in the level of liver pseduocholinesterase (as much as 93%) was recorded in the treated animals under identical conditions of administration of both the complexes. Hepatic uptake studies revealed that within 5 min, maximal sequestration of IC occurred within the liver (10 to 18%) and the blood (70 to 82%) when computed in terms of total injected radioactive IC. After 4 h, radioactivity dropped to 3 per cent in liver and 50-40 per cent in blood. The liver seemed to be incapable of scavenging all the serum complexes at a time. Significant consumption of serum complement occurred, when freshly prepared complexes were administered to the animals, but the reduced complement level showed a tendency to reach normalcy after 2 h. The soluble and equivalence zone IC failed to exhibit identifiable discrimination facets with respect to handling by liver. The complexes IC-E and IC-S also behaved in a similar manner.
Acid Phosphatase↗
Solubilization of preformed immune complexes in sera of patients with type 1 and type 2 lepra reactions.
Serum complement activity in leprosy patients has been studied using solubilization of preformed immune complexes as an index. The solubilization capacity of sera from lepromatous patients with or without erythema nodosum leprosum (ENL) as well as from type 1 reactional patients was found markedly reduced as compared to controls. Solubilization did not improve at all in the ENL patients after remission of the reaction phase. The addition of fresh normal sera failed to bring about any significant restoration of solubilizing capacity of the deficient sera. Mycobacterium leprae sonicate significantly reduced the solubilization capacity. Our results suggest that circulating mycobacterial breakdown products possibly interfered with the capacity of the ENL patients' sera to solubilize immune complexes.
Adolescent↗
Undernutrition and lepromatous leprosy. III. Micronutrients and their transport proteins.
The present report is a continuation of our earlier studies on the complex interaction between undernutrition and leprosy. Serum levels of vitamins A and E, zinc and iron were determined in healthy control subjects and lepromatous leprosy patients belonging to an eastern state of India. Results indicated a significant lowering in the two above-mentioned fat-soluble vitamins and also a remarkable hypozincaemia in the patient group. However, serum iron levels were found to be comparable in both the groups. Also concentrations of vitamin A transport proteins such as retinol binding protein and prealbumin in sera of the lepromatous patients were significantly decreased in comparison with the control subjects. Of the two zinc-binding proteins, ie, serum albumin and alpha-2 macroglobulin, only the former was significantly reduced in the patient group. Surprisingly, though serum iron, transferrin and ferritin levels were similar in both the patient and control groups, the haemoglobin levels were significantly reduced in the lepromatous patients. The implications of these findings have been discussed. This is the first report describing the serum ferritin levels in lepromatous patients.
Adolescent↗
Effects of chloroquine on the serum complement system.
Chloroquine, a well-known anti-malarial and anti-inflammatory agent, was studied with respect to its effect on the serum complement system. The drug exhibited significant in vitro anti-complementary activity only at a very high non-therapeutic dose of 48 mg/ml. Chloroquine-induced in vitro complement consumption was observed to take place even in the absence of Ca2+ and Mg2+ ions. The drug also haemolyses rabbit erythrocytes in the presence of Mg2+-EGTA and immunoelectrophoretic studies of fresh human serum and chloroquine incubation mixture against specific anti-C3 and anti-factor B antisera have demonstrated that it cleaves both C3 and factor B. In another experiment, chloroquine failed to exert inhibitory effects on complement utilisation by immune complexes. Studies of the serum complement profile of Plasmodium falciparum-infected malaria patients receiving chloroquine therapy indicated that, in contrast to the situation in vitro, the serum C3 level is invariably decreased. Marginal reductions in the levels of C4, factor B and properdin were also found in some of these patients, while administration of chloroquine to normal human individuals failed to produce any significant change in their serum complement profile. It is, therefore, probable that malarial parasites and not chloroquine are responsible for complement activation in patients suffering from malaria.
Adult↗
Enzyme immunoassay of serum beta-2-microglobulin levels in various histological forms of leprosy with special reference to its elevation in type I and type II lepra reactions.
The mean beta-2-microglobulin level in serum (3,362 +/- 2,494 micrograms/liter) for 76 leprosy patients, including 9 borderline-tuberculoid, 8 borderline-borderline, 9 borderline-lepromatous, and 16 lepromatous-lepromatous patients and 34 patients with type I or type II lepra reactions, was significantly higher (P less than 0.001) than that (2,122 +/- 1,844 micrograms/liter) for 35 normal subjects. It decreased significantly (P less than 0.001) as the disease glided down from borderline tuberculoid (3,173 +/- 899 micrograms/liter) to the lepromatous end (1,813 +/- 1,391 micrograms/liter). At the onset of type I or type II reaction, the mean beta-2-microglobulin level in serum increased (4,447 +/- 2,863 micrograms/liter), and it remained unchanged (4,433 +/- 2,623 micrograms/liter) after clinical remission. The beta-2-microglobulin level in serum decreased in 55.5% of the patients tested after subsidence of reaction. The level was significantly higher in patients with type II reactions (5,433 +/- 3,299 micrograms/liter) than in patients with type I reactions (3,558 +/- 2,171 micrograms/liter).
Adolescent↗
Radioimmunoassay of serum cortisol levels in leprosy patients with special reference to type I and type II reaction.
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Adolescent↗
Polyethylene glycol precipitates in serum during and after erythema nodosum leprosum--study of their composition and anticomplementary activity.
Polyethylene glycol (PEG) precipitates obtained from sera were characterized and quantitated in 20 borderline lepromatous (BL) and polar lepromatous (LL) patients with moderate to severe erythema nodosum leprosum (ENL) before and four weeks after treatment with anti-ENL drugs, e.g., cortisone, clofazimine, chloroquine, or aspirin. Although the clinical severity of ENL subsided, there was no significant clearance of material that precipitates with PEG from the circulation. These precipitates had variable anticomplementary properties.
Antigen-Antibody Complex↗
Breakdown product of factor B as an index of complement activation in lepromatous leprosy and its relation with bacillary load.
Serum complement profile studied in 50 lepromatous leprosy patients with various bacillary loads demonstrated significantly decreased C3 levels in patients with high bacteriological index (2+ to 4+) as compared with those with lesser bacterial load. In contrast, mean serum levels of C1q and C4 components remained unchanged. The concentration of factor B breakdown product (Ba) and its ratio to factor B increased with the bacterial density and more so in patients with erythema nodosum leprosum. A significant negative correlation was found between serum C3 and Ba levels in most lepromatous patients. Analysis of the data suggested the alternative pathway as the possible mechanism of complement activation in lepromatous leprosy.
Adult↗
Haemoglobin E-beta-thalassaemia; a study of eight cases in Northwest India.
Eight cases of haemoglobin E-beta.thalassaemia are described. Seven of them are natives of Punjab, a Northwest province of India, and one is a native of Rajasthan, a province adjacent to Punjab. Hb E is rarely encountered in Punjab, but beta-thalassaemia is relatively common. The interaction of Hb E with beta-thalassaemia resulted in a varying severity of phenotypic manifestations. An extraordinary feature in 3 out of 8 cases was the presence of a high percentage of Hb E (94 to 96%) and proportionately low Hb F (4 to 6%). The interacting thalassaemia in 5 patients was of beta0 type and in 3 patients of beta+ type.
Adolescent↗
Identification of components of IC purified from human sera. II. Demonstration of mycobacterial antigens in immune complexes isolated from sera of lepromatous patients.
Immune complexes have been purified from sera of patients with lepromatous leprosy, using solid phase conglutinin and analysed by SDS-PAGE. Some of their components have been immunologically identified after electrophoretic blotting on nitrocellulose. First, immunoglobulins, complement components (C1q, C1s, C3) and CRP were found in IC. Secondly, one mycobacterial antigen of 67 kD was directly identified in IC while two other components (20 kD and 14.4 kD) of possible M. leprae origin were also found in IC. This study suggests that lepromatous patients develop a good antibody response against some M. leprae antigens (33 kD and 12 kD), which are rapidly eliminated from circulation, while other M. leprae antigens (e.g. 67 kD) can persist in relative antigen excess, within circulating IC.
Antigen-Antibody Complex↗
SDS-PAGE analysis of M. leprae protein antigens reacting with antibodies from sera from lepromatous patients and infected armadillos.
Studies have been conducted to characterize M. leprae bacilli derived from infected armadillos. First, the proteins of the mycobacterial extracts were fractionated by SDS-PAGE. Subsequently, the proteins in the gel were electrophoretically transferred on a strip of nitrocellulose paper by the technique of 'electrophoretic blotting'. The separated bacterial protein bands, thus immobilized on the nitrocellulose paper were made to react immunologically with sera from the lepromatous patients, infected armadillo sera and other experimental mycobacterial antisera. It was observed that a majority of M. leprae proteins contained antigenic determinants also present on proteins of BCG. In addition, only two specific antigen bands of 33KD and 12KD were conspicuously detected by the patients' sera and the infected armadillo sera. These substances were further identified as polysaccharides or glycoproteins since they could only be stained by Schiff's reagent or alcian blue. Only 12KD glycoprotein band reacted with concanavalin A, whereas wheat germ agglutinin (WGA) did not show any reaction with them. These 33KD and 12KD glycoprotein antigens were found to lose their antigenicity after pepsin treatment and can be considered as glycoproteins. Further, radiolabelling experiments showed that 12KD antigen underwent radioiodination under usual conditions, but 33KD glycoprotein failed to be similarly radiolabelled. It is suggested that these protein antigens have M. leprae specific determinants on a cross-reacting component.
Animals↗
Hepatic involvement in ascitic type of tuberculous peritonitis.
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Ascites↗
Effects of antibacterial agents on the complement system.
The alteration of serum complement profile following therapy with various antibiotics was studied in 23 hospitalized patients and in 10 human volunteers. Tetracycline, chloromycetin, ampicillin, and streptomycin reduced serum CH50 and C3 levels in the inpatients. Tetracycline administration for three consecutive days in four normal subjects decreased serum CH50, C1q, C3, and C4 levels on day 4. However, these parameters returned to near-normal levels on day 7 following the withdrawal of the drugs. On the other hand, septran administered in six normal individuals for three consecutive days had no significant effect on the complement system. In vitro studies as well as in vitro studies in guinea pigs treated with various antibiotics showed almost parallel results.
Animals↗