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PubMed1987

Cellular and humoral immune response to a phenolic glycolipid antigen (PhenGL-I) in patients with leprosy.

The ability of phenolic glycolipid I (PhenGL-I) of Mycobacterium leprae to stimulate in vitro lymphocyte proliferation (LP) was tested in cultures of peripheral blood cells from 42 patients with leprosy in Chicago and Thailand, 9 individuals with household contact in Thailand, and 10 unexposed North American controls. Only 10 responders (24%) were found among the patients, and the degree of LP was small. Responders were found among patients with lepromatous (18%) or tuberculoid (30%) leprosy without relation to age, complications, duration of treatment, or lepromin responsiveness. The specificity of the response was supported by a lack of response to two other glycolipids, by responses by T cells but not B cells, and by the observation that three of four responders tested maintained their responses to PhenGL-I for at least 1 year. Serum immunoglobulin M (IgM) and IgG antibodies were measured in the same patients by using PhenGL-I or its terminal monosaccharide conjugated to a bovine serum albumin carrier in an enzyme-linked immunosorbent assay. The presence of IgM antibody correlated negatively with LP to lepromin and to PhenGL-I in patients with tuberculoid leprosy. We conclude that circulating T cells from some leprosy patients proliferate in the presence of PhenGL-I in vitro, but the response is weak, possibly due to concomitant suppression or inhibition. The predominance of IgM antibody to PhenGL-I may be related to a lack of a T-helper-cell-mediated switch to IgG antibody response.

Antibodies, Bacterial↗
PubMed1989

Leprosy in children: correlation of clinical, histopathological, bacteriological and immunological parameters.

The study of leprosy in children has indicated an incidence of 10% amongst leprosy patients attending the clinic. The duration of the disease was usually less than 2 years. The expression of leprosy in this group was either a macule and/or a plaque. Classification was, therefore, different and conforms to indeterminate (I), borderline tuberculoid (BT) and borderline (BB) leprosy. Only occasionally were other clinical variants seen. The bacteriology was largely unproductive by slit-skin smears. The lepromin (Mitsuda) responses were positive in BT and unpredictable in BB patients. Epicutaneous responses to sensitization with dinitrochlorobenzene (DNCB) paralleled responses to lepromin. Microscopic pathology was of very little help. The correlation of these parameters was only 50-60% indicating that the diagnosis of leprosy should primarily be based on clinical features.

Adolescent↗
PubMed1996

Borderline--tuberculoid leprosy: clinical and immunological heterogeneity.

The authors analysed some immunological criteria in leprosy patients diagnosed as borderline tuberculoid by the presentation of different grades of skin lesions as well as different grades of nerve involvement. Only 50% of the patients presented a single skin lesion and 58% had none or only one affected nerve. Nineteen patients (39.6%) showed a positive lepromin reaction (induration > or = 5 mm). Patients with a positive skin test had a greater number of skin lesions when compared with patients with a negative lepromin test. Fifty-seven percent of the patients were found to be positive using a lymphoproliferation test (LTT) in response to Mycobacterium leprae antigens. Positive LTT results did not correlate with the number of skin lesions, but patients unresponsive to LTT had a lesser extent of nerve involvement. Four out of 18 patients (22%) released high IFN gamma levels in PBMC culture stimulated by M. leprae. (mean U/ml +/- SD = 142 +/- 72). All of these 4 patients presented only one skin lesion, although three of them had more than one affected nerve. Nineteen out of 21 patients (90.5%) showed no anti-PGL-1 antibodies in their serum. The low levels of anti-PGL-1 antibodies among these patients confirmed their tuberculoid background even in those with multiple skin lesions. These findings seem to attribute an important role to IFN gamma in restraining the spreading of the infection in the skin, but IFN gamma may have an opposite effect on the nerves. The potential pathological effects of IFN gamma during the delayed type of hypersensitivity can be related to its ability to synergise with other inflammatory cytokines such as TNF alpha, IL-1 beta, and others.

Adolescent↗
PubMed1976

Delayed hypersensitivity tests with Mycobacterium leprae purified protein derivative.

Skin tests were conducted on 3 lepromatous, 3 dimorphous and 6 tuberculoid leprosy patients and 3 others not suffering from leprosy with lepromin, purified protein derivative from M. leprae of armadillo origin and tuberculin. Results show that a delayed hypersensitivity reaction could be produced with PPD in 72 hours on all Mitsuda positive cases, with one anomalous exception, without cross reaction to tuberculin. The results were promising from the point of view of substituting lepromin with PPD in usual tests.

Animals↗
PubMed2001

Impact of combined Mycobacterium w vaccine and 1 year of MDT on multibacillary leprosy patients.

A total of 20 bacteriologically positive multibacillary (MB) leprosy patients older than 18 years of age with a bacterial index (BI) of 2+ or greater were given standard World Health Organization multiple drug therapy (MDT-MB) for 12 consecutive months plus four intradermal doses of Mycobacterium w vaccine at 3 monthly intervals (Study group). Twenty age-matched MB patients were given WHO/MDT alone (Control group). The patients of both groups were followed up for 1 year. Improvements in the patients were periodically monitored by clinical (Ramu's score), bacteriological (SSS), histopathological (skin biopsy) and immunological (lepromin conversion) parameters. Study group patients showed more significant improvements in all parameters except for lepromin conversion compared to patients in the Control group. The incidence of type 1 reaction was more in the Study group (30% vs 10%), while the incidence of type 2 reaction was more in the Control group (25% vs 15%). Neuritis associated with reactions was seen more often in the Control group compared to the Study group (20% vs 10%). The addition of Mycobacterium w vaccine as an adjunct to the 1-year WHO/MDT regimen appears to be significantly more beneficial in MB leprosy patients with a high initial BI compared to WHO/MDT given alone. Studies on larger numbers of patients with extended follow up will be in order.

Adult↗
PubMed2005

Reversal reaction and Mitsuda conversion in polar lepromatous leprosy: a case report.

A 22-year-old male polar lepromatous leprosy patient who became Mitsuda positive after 36 months of multidrug therapy (MDT) is reported. Lepromatous leprosy (LL) is a state of specific immunosuppression and is invariably irreversible. The finding of Mitsuda positivity in histopathologically proven polar lepromatous leprosy is extremely uncommon, and conversion of lepromin status following MDT has not so far been reported. This case reports confirms the observations made by Waters et al. regarding lepromin conversion in lepromatous patients.

Adult↗
PubMedDate not supplied

Nine-banded armadillo (Dasypus novemcinctus) as an animal model for leprosy.

Dr. Dharmendra was one of the most distinguished leprologists of our time. He loved India so much that he offered his entire life to fight leprosy, a major health problem in India. He realized the great need in this much neglected field of medicine and willingly gave his utmost, whatever be the cost. He served in the field of leprosy with great distinction and he earned the respect of his fellow workers from all over the world. He made outstanding contributions to the study of leprosy, the identification and isolation of the active principle in the lepromin reagent, the use of lepromin test for identifying persons susceptible to leprosy, the use of an antileprosy drug as a means of chemoprophylaxis, the nurturing of the Indian Journal of Leprosy and developing it as one of the foremost leprosy journals, are a few of his major contributions. He received many well deserved national and international honours and awards. I first met Dr. Dharmendra in 1956 and feel privileged to have known him and to be associated with him all these years. I am honored to be asked to contribute this paper for a publication meant to pay tribute to his memory.

Animals↗
PubMed1990

Reflections on some aspects of leprosy among children in Brazil and in other countries.

The authors discuss the classification, clinical aspects, lepromin reactivity, and epidemiologic features of leprosy among children. The most frequent characteristics of each form of leprosy are described. Lepromatous leprosy is less frequent among children in countries of low endemicity and more frequent, even in the most advanced forms, in hyperendemic regions. Borderline forms are rare. In a large number of cases the initial manifestations are those of the indeterminate form and, in an even larger number of cases, of the tuberculoid pole. The evolution from indeterminate to the tuberculoid pole very frequently occurs in a few months or within less than one year. With respect to epidemiology, the authors consider the general frequency of leprosy among children and the frequency of each form of leprosy among children and adults. Data from surveys carried out in Brazil and other countries are presented. Children have a potential for the rapid development of immunoresistance and consequently of lepromin-positivity, and therefore only a few of them eventually develop lepromatous leprosy. This explains the low indices of lepromatous leprosy (approximately 5%) even in hyperendemic areas. Finally, they discuss the factors that may be responsible for the clinical manifestations of leprosy and their characteristics among children.

Adolescent↗
PubMed1986

In situ and in vitro characterization of the cellular immune response in erythema nodosum leprosum.

We sought to evaluate cell-mediated immune responses in erythema nodosum leprosum (ENL), a reactional state occurring in lepromatous leprosy. Skin biopsies from patients with leprosy were studied with monoclonal antibodies against T lymphocyte antigenic determinants, interleukin 2 (IL 2), and IL 2 receptors (Tac) by using immunoperoxidase staining of frozen sections. Peripheral blood lymphocytes from 18 ENL patients were tested in vitro for lepromin-induced suppression of Con A stimulation. Serial studies of seven lepromatous patients who developed ENL during the course of the study showed increases in both the Leu-3a:Leu-2a ratio and the number of IL 2-positive cells. IL 2-positive cells comprised 0.3% of the cells in all of the ENL lesions studied as compared with the 0.03% found in nonreactional lepromatous lesions (P less than 0.001). Lepromin-induced suppression of the Con A response, present in nonreactional lepromatous patients, significantly decreased in patients developing the ENL reaction, but returned after recovery from ENL. These changes in tissues and peripheral blood suggest that the pathogenesis of ENL is related to cell-mediated immune processes. Despite these immunologic changes, however, ENL patients do not recover antigen-specific skin tests or eliminate Mycobacterium leprae.

Antibodies, Monoclonal↗
PubMed1988

T and B cells in borderline (BB) leprosy.

The response to standard Dharmendra lepromin and the circulating T, B cell numbers in the peripheral blood were quantitated in 15 patients with Borderline (BB) Leprosy. On the basis of lepromin response, the patients fall into three groups (a) negative (b) +/- reaction (c) rarely positive. No significant difference in the numbers of E-rosette and EAC rosette forming cells was observed in the BB patients in comparison to controls.

B-Lymphocytes↗
PubMed1988

Soluble antigen of M. leprae coupled with liposomes elicits both "early" and "late" delayed hypersensitivity skin reactions.

The soluble antigen(s) of Mycobacterium leprae was(were) coupled to liposomes and used for skin testing of leprosy patients, hoping that this mode of antigen presentation would be identical to that of integral lepromin. The liposomized antigen(s) elicited both early (24-48 hr) and late (3-4 weeks) delayed-type hypersensitivity reactions, true to the nature of lepromin, unlike the soluble antigen(s) alone which elicit(s) only the early reaction.

Antigens, Bacterial↗
PubMed1987

Assessment of the immune deficit in leprosy patients and the effect of recombinant IL-2 in vitro.

Although the mechanism of immunologic unresponsiveness in lepromatous leprosy remains unknown, it has been shown that interleukin-2 (IL-2) production is defective in these patients. Peripheral blood mononuclear cells (PBMC) were isolated from treated (less than 16 months) and untreated leprosy patients as well as household contacts; age, sex, ethnically matched control subjects; and laboratory staff. PBMC were cultured for 6 days with sonicated Mycobacterium leprae (1-10 micrograms/ml), Dharmendra lepromin (1:10), or phenolic glycolipid-I (PGL-I) (0.05-5.0 micrograms/ml) in medium supplemented with various concentrations of recombinant IL-2 (rIL-2) or cultured for 3 days with one of the three mycobacterial antigens in the presence of concanavalin A (ConA). TT/BT patients and household control subjects had a robust response to M. leprae and lepromin, but were unresponsive to PGL-I delivered in liposomes. PBMC from LL patients did not respond to any of the three antigen preparations. rIL-2 induced proliferation of PBMC both in leprosy patients and control subjects regardless of the presence or absence of the three leprosy antigen preparations. This antigen nonspecific augmentation of proliferation by the wide range of doses of rIL-2 employed makes difficult the interpretation of the enhanced thymidine incorporation noted when rIL-2 is added in the presence of antigen to cultures of lymphocytes from LL patients. Our studies are at variance with reports that leprosy antigens, specifically PGL-I, induce immunological suppression, in that mycobacterial antigens did not cause significant suppression of the ConA-induced proliferations of PBMC from patients.

Adolescent↗
PubMedDate not supplied

Immunotherapy in leprosy: a new approach.

An immunotherapeutic agent prepared from patient's own affected skin was tried in 30 leprosy cases. 53.6% cases of lepromatous and borderline lepromatous group showed lepromin conversion from lepromin negativity to positivity after 12 weeks of immunotherapy. The clinical and bacteriological improvement was also good. 88.1% cases of borderline tuberculoid also showed fair to good clinical recovery following 12 weeks of immunotherapy.

Humans↗
PubMed1979

Immunological changes observed in indeterminate and lepromatous leprosy patients and Mitsuda-negative contacts after the inoculation of a mixture of Mycobacterium leprae and BCG.

This investigation was carried out to study the possibility of eliciting favourable immunological changes in small groups of Mitsuda-negative patients with indeterminate leprosy, lepromatous patients who were bacteriologically negative after prolonged treatment with sulphones, and in Mitsuda-negative contacts by means of stimulation with a mixture of autoclaved tissues from Mycobacterium leprae-infected armadillos and living BCG. A radical change was observed in the specific immunological activity of the indeterminate group, all of whom initially had occasional bacilli in cutaneous nerves in biopsies taken from hypopigmented spots, and in the persistently Mitsuda-negative contacts. The 48 hr and 30 day reactions to lepromin, the 48 hr reaction to supernatant antigen from lepromin, the test for bacillary clearence and in vitro lymphocyte transformation (LTT) to M. leprae from human and armadillo lesions all became positive. Of the lepromatous patients studied, only one became positive to all the criteria mentioned above. In the others, the 48 hr reaction to supernatant antigen, the LTT to antigen from a humn source, and the clearance test remained negative, while the Fernandez and Mitsuda reactions became positive. These results are discussed in terms of the possible use of this stimulation procedure in the prevention and immunotherapy of leprosy.

Adolescent↗
PubMed1985

HLA-linked control of predisposition to lepromatous leprosy.

In order to investigate if genes conferring susceptibility to leprosy and/or predisposition to a particular leprosy type are linked to HLA, we performed HLA-A and HLA-B typing on members of 29 families containing at least two siblings affected with leprosy from a leprosy endemic area in Jiangsu Province, People's Republic of China. Moreover, we performed a lepromin test in nearly all of the members of eight families containing at least two siblings affected with lepromatous leprosy. For 26 families the data permitted analyses of the segregation of parental HLA-haplotypes observed among children in relation to leprosy status. Siblings affected with lepromatous (LL or BL) leprosy shared parental HLA-haplotypes significantly more often than expected (p less than 0.05), and a highly significant deficit (p less than 0.0005) of shared HLA-haplotypes was observed among affected siblings discordant for leprosy type. These data confirm the HLA-linked control of leprosy type and, in particular, recently obtained evidence for linkage of predisposition to lepromatous leprosy with HLA. Healthy siblings did not share a haplotype more often than expected, and those haplotypes which were shared among all leprosy patients of a sibship did not occur less frequently than expected among the healthy siblings of the same sibship. The latter data confirm the absence of linkage of genes conferring susceptibility or resistance to leprosy with HLA. An analysis of the lepromin test results observed among healthy siblings showed no evidence for cosegregation of the results with HLA.

Child↗
PubMed1985

A study of the immunological effects of cimetidine in patients with lepromatous leprosy.

To test the capacity of cimetidine to enhance cellular immunity in patients with lepromatous leprosy (LL), cimetidine was given for one month to 29 inactive LL patients and 3 active LL patients. Immune function was monitored with skin tests (lepromin, PPD, candida, and trichopytin), lymphocyte transformation tests (phytohemagglutinin, BCG, and Dharmendra lepromin), and quantitation of peripheral blood lymphocyte subpopulations. A small but significant "booster" response to PPD was the only change observed in the study of patients with inactive disease, and leprosy-related reactions did not occur. In the few active LL patients studied, neither immune enhancement nor leprosy-related reactions were observed. The results of this investigation suggest that cimetidine can be used safely in patients with inactive lepromatous leprosy.

Adjuvants, Immunologic↗
PubMedDate not supplied

Leucocyte migration inhibition response of Mycobacterium habana with sensitized animals and cells from leprosy patients.

Response of Mycobacterium habana sensitized mouse cells against habanin (sonicated extract) lepromin (Dharmendra) and tuberculin has been studied in the leucocyte migration inhibition test. The homologous antigenic response has evoked maximum inhibition as compared to heterologous antigens but close antigenic association has also been observed with lepromin and tuberculin. With human cells from leprosy patients these antigens have evoked analogous response indicating cross immunogenicity of M. habana with leprosy sensitized cells.

Animals↗