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PubMed1989

Specific anti-M leprae PGL-I antibodies and Mitsuda reaction in the management of household contacts in New Caledonia.

Household contacts of leprosy patients have been tested for anti-phenolic glycolipid-I IgM antibodies (anti-PGL-I IgM) by an ELISA using the natural disaccharide (NDO) and natural trisaccharide (NTO) synthetic antigens. A group of healthy subjects without known exposure to Mycobacterium leprae served as controls. The percentages of positivity observed in multibacillary patients, paucibacillary patients, and household contacts were significantly higher than those of the negative controls. The absorbance values using NDO and NTO correlated well (range 0.59-0.91) when analysis of each subject group was performed. As reported here, NDO and NTO antigens seem to be equal in detecting leprosy cases; 100% of multibacillary and 21.43% of paucibacillary cases were detected as seropositive. For the screening of household contacts, NDO appears to be more sensitive and NTO more specific. There were more seropositive cases in the young age groups of household contacts, suggesting a higher rate of transmission of M. leprae infection in those age groups. Lepromin and anti-PGL-I IgG tests were also performed in contacts who were followed. The 2 paucibacillary subjects (1 borderline tuberculoid, 1 indeterminate) were Mitsuda negative. At diagnosis, their anti-PGL-I IgM levels were much higher than those of previous results; their anti-PGL-I IgG levels showed an increase in one and a decrease in the other. However, for the entire group anti-PGL-I IgM and anti-PGL-I IgG levels were positively correlated. The data reported here suggest that an increase in specific anti-M. leprae IgM levels in Mitsuda-negative household contacts could reveal the development of overt disease.

Adolescent↗

PubMed1989

Relapses in paucibacillary patients after treatment with three short-term regimens containing rifampin.

Three multidrug regimens all containing rifampin and dapsone have been tried for the treatment of 278 cases of paucibacillary leprosy. Regimen I was the one recommended by the WHO Study Group. Regimen II was the same as Regimen I with depsone alone continued for a further 6 months. Regimen III was the same as Regimen II but rifampin was given daily for the first 7 days. The patients were comparable with regard to disease classification, lepromin status, bacteriological status, and number of lesions. As reported earlier, the disease inactivity rates by 1 year of treatment were much greater with Regimens II and III than with Regimen I (94% and 97% vs 76%). Early reaction was seen in 6% of those in Regimen III and in none in Regimens I and II. Late reaction was observed in 9% of those in Regimen I and none in Regimens II and III. During 3 1/2 years of follow up, 13% of the cases in Regimen I, 1% in Regimen II, and 2% in Regimen III relapsed. Since the patients in the three regimens were otherwise comparable, it is concluded that the high inactivity rate, low relapse rate (1%-2%), and no early or late reaction as observed in Regimen II patients were because of adequate treatment.

Adult↗

PubMed1986

Suppressor T lymphocytes from lepromatous leprosy skin lesions.

The immune response in leprosy forms a spectrum with lepromatous leprosy patients exhibiting specific unresponsiveness to antigens of Mycobacterium leprae. This unresponsiveness is thought to be related to the prevalence of T8-positive lymphocyte in these lepromatous lesions. To analyze the immunoregulatory function of these T8 cells, we developed simple procedures to extract lymphocytes from skin biopsy specimens of patients with leprosy. These lymphocytes were sorted for T8 and T4 positive cells, and cell lines were established by expansion with interleukin 2 (IL 2) and irradiated feeder cells. All T8 positive lines tested were positive for IL 2 receptors and HLA-DR determinants. These lines were additionally assayed for lepromin-induced suppression of the normal peripheral blood lymphocyte Con A proliferative response. Thirteen of 32 lines from six lepromatous patients showed significant suppressor activity, whereas nine lines from six tuberculoid patients and one line from normal peripheral blood failed to show suppression (p less than 0.001). Taken together, the finding of M. leprae-triggered suppressor cells within lepromatous skin lesions may in part explain the M. leprae unresponsiveness of lepromatous leprosy patients.

Antigens↗

PubMed1988

Evidence of cell-mediated immune contrasuppression in lepromatous leprosy: modulation of a putative T contrasuppressor cell-subset.

Some lepromatous leprosy (LL) patients are characterized by the presence of activated suppressor T cells that specifically inhibit the immune response to Mycobacterium leprae antigens. Immune contrasuppressor (CS) cell activity antagonize suppressor function. Whereas the former function has been extensively studied in leprosy, the latter has not been explored. We studied the peripheral blood mononuclear cells (PBMNC) of 20 patients with leprosy (10 lepromatous and 10 tuberculoid) and six healthy contacts. We found CS-like activity in the PBMNC from some LL patients when assayed in vitro using lepromin as antigen. This CS-like function was found in CD8+, vicia villosa adherent (VV+) T cells. CS-like activity was not detected in PBMNC from either tuberculoid patients or healthy contacts. Pre-treatment of CD8+, VV+ cells with either recombinant IL-2 (5 u/ml) or recombinant interferon-gamma (1,000 u/ml) did not modify significantly their putative CS function. However, in 50% of lepromatous patients the pre-incubation of CD8+, VV+ cells with both lymphokines together increased significantly the CS-like activity. These data suggest that the in vitro immune response to M. leprae in some LL patients can be augmented by either modifying numerically the contrasuppressor T cells or activating them with lymphokines.

Antigens, Bacterial↗

PubMed1979

T and B lymphocytes and blastogenesis in leprosy.

T and B cell percentages and their blastogenic response to PPD and lepromin have been studied in 107 patients of various types of leprosy. T cell counts and their blastogenic response were found to be considerably lower in all types of leprosy as compared to the normal. The counts and stimulation were the lowest for lepromatous leprosy. B cell counts were unaltered in all types of leprosy.

Adult↗

PubMed1986

ICRC vaccine-induced changes in M. leprae-specific cell-mediated immunity in langur (Presbytis entellus) monkeys.

The effects of the administration of ICRC antileprosy vaccine on skin reactions and lymphocyte transformation tests (LTT) to antigens of Mycobacterium leprae have been investigated in Hanuman langur monkeys (Presbytis entellus) which live native to north India. In a majority of these monkeys, the vaccine brings about lepromin conversion associated with a change in tissue response consistent with "ugrading" of immunity. However, no concomitant changes were observed in the LTT. The significance of these observations is discussed. It is proposed that the langur monkey could be used as a laboratory model to screen "candidate" antileprosy vaccines.

Animals↗

PubMed1986

Adoptive transfer of tolerance induced by ICRC bacilli against Mycobacterium leprae in mice.

ICRC bacilli, the cultivable leprosy-derived mycobacteria, isolated from lepromatous nodules of leprosy patients were found to be immunogenic in BALB/c mice at a dose of 2 X 10(7) acid-fast bacilli when injected by the intradermal (i.d.) route. The sensitization to lepromin and ICRC antigens was measured by the foot pad enlargement (FPE) method. The same dose of bacilli when injected by intravenous (i.v.), intraperitoneal, and subcutaneous routes induced immune tolerance in mice as indicated by reduction in the FPE to the test antigens. The spleen cells obtained after i.v. injection of ICRC bacilli/Mycobacterium leprae after adoptive transfer brought about suppression of delayed-type hypersensitivity in sensitized as well as nonsensitized recipients, indicating production of suppressor cells after i.v. injection. Similarly, the tolerance induced by i.v. injection of M. leprae in mice could be partially converted to immunity by i.d. sensitization with live BCG and two strains of ICRC bacilli (C-44 and C-75).

Animals↗

PubMed1986

Lymphocyte transformation in lepromatous leprosy: a study of the influence of disease activity and symptom duration.

The lymphocyte hyporesponsiveness to M. leprae of patients with active lepromatous leprosy has been well described. This immune defect is less well understood in terms of its time of origin, possible reversibility and specificity. To further examine the persistence and specificity of this abnormality, lymphocyte transformation tests of 93 leprosy patients to lepromin, BCG and PHA were studied. Among lepromatous patients, a decreased response to M. leprae was seen, whether the disease was active or inactive. Decreased responses to BCG were found in lepromatous patients with active disease, but not in those with inactive disease. The duration of patient symptoms was not associated with differences in LTT responses among the active lepromatous patients.

Adolescent↗

PubMed1985

An in situ immunohistological study of Mitsuda reactions.

In an attempt to further define their immunopathogenesis, the cellular infiltrates of Mitsuda reactions were studied in situ using immunoperoxidase techniques and monoclonal antibodies. Lepromin A-elicited Mitsuda reactions from six patients with borderline tuberculoid leprosy (TT/BT or BT) and three healthy kindred and contacts of lepromatous patients were examined. In the dermis, cells bearing the Leu4 phenotype comprised a mean of 61% of the infiltrate; the Leu3a, 47%; the Leu2a, 17%; anti-IL-2, 0.2%; anti-Tac, 1.5%; and cells bearing the Ia phenotype were virtually universal; OKT6 positive cells were present. The Leu2 phenotype was sequestered to the periphery of epithelioid tubercules. In the epidermis, there were mild, focal lymphocytic infiltrates, hyperplasia of epidermal Langerhans' cells, and well-developed expression of Ia upon nucleated keratinocytes. These findings, when compared with those of a better-defined reaction, tuberculin, are further evidence that the Mitsuda response may be a delayed-type hypersensitivity phenomenon.

Humans↗

PubMed1973

Immunological problems in leprosy research. 1.

This Memorandum reviews the present status of knowledge of the immunology of leprosy, with particular attention to developments since the publication of a similar review in 1970. The different types of lepromin reaction and their significance in healthy contacts and in patients with tuberculoid and lepromatous leprosy are discussed. The immunological responsiveness of patients with leprosy is also considered, with special attention to in vitro methods for evaluating this response. Part 2 of the Memorandum will cover possible mechanisms of altered immune response in leprosy (including a tentative scheme to explain the possible genesis of the lepromatous lesion); genetic, nutritional, and hormonal factors; the possibility of vaccination; attempts at immunotherapy; and areas in which further research is needed. A detailed protocol for evaluating the effect of transfer factor in leprosy will be included as an annex.

Antibodies, Bacterial↗

PubMed1979

Immune deficit in patients with lepromatous leprosy: its nature and relation to genetic factors, spectrum, and duration of the illness.

Cell-mediated immunity or hypersensitivity to M. leprae and other unrelated antigens, such as tuberculin and dinitrochlorobenzene, was studied in 73 leprosy patients of different histopathologic types. It was found that specific as well as nonspecific anergy intensified as the disease spectrum shifted from the tuberculoid toward the lepromatous immunologic pole. Within the lepromatous group, the impairment of cellular immunity became more pronounced as the bacillary load increased. It was found that the impairment of the cell-mediated immunity towards antigens other than M. leprae became more severe as the duration of the illness increased. Late lepromin responsiveness, which is the hallmark of resistance of an individual to M. leprae, may be absent even before the onset of clinical illness. Its deficit seems to be primary and has a genetic predisposition.

Adult↗

PubMed1979

Immunologic shin titration in leprosy patients and contacts.

A method of studying delayed-type hypersensitivity was developed with specific antigen in leprosy patients and contacts, measuring the dose-response curve at different lepromin concentrations. This "immunologictitration" is highly efficient for discriminating the degree of hypersensitivity reactions among the groups tested. With respect to the Fernandez reaction, the results obtained showed that there was a similar behavior in all groups studied, except in the tuberculoid group which had a more intense response, four times higher than that yielded by contacts of lepromatous patients. In the Mitsuda reaction, a similar behavior was also found among the different groups, except with respect to the reactivity intensity of contacts of lepromatous patients. Here it was demonstrated that this group had a significant depression in response to M. leprae antigen when compared with that from the other groups, independent of the degree of consanguinity or closeness to bacilliferous cases. In order to explain this immunosuppression in contacts of lepromatous patients, a hypothesis is proposed. It is suggested that changes could occur in M. leprae derived from lepromatous patients, diminishing their capacity to produce an adequate immune response.

Adolescent↗

PubMedDate not supplied

Antigeneic cross-reactivity between ICRC-bacilli and M. leprae--"in vitro" evaluation.

Leucocyte migration inhibition, in presence of specific particulate antigen, is a good correlate of CMI. It can detect small differences in related antigens. In the present study, LMI was used to study the cross-reactivity between ICRC bacilli and M. leprae and also to examine the antigenic relationship amongst different ICRC isolates. The study showed a close antigenic cross-reactivity in lepromin and ICRC-in. LMI has brought out strain differences in two ICRC culture isolates, C-44 and C-75. The data appear to elucidate the possible strain specific antigenic relationship of M. leprae with its culture isolate e.g. ICRC strains. This may have important bearing on the development effective antileprosy vaccine for human use.

Animals↗

PubMedDate not supplied

DNCB contact sensitization in leprosy: its comparison with other CMI tests.

76 Lepromatous, 50 non-lepromatous cases of leprosy and 20 apparently healthy individuals were tested for Dinitrochlorobenzene contact sensitization. Only one lepromatous case and one apparently healthy individual showed negative result. E-rosette counts and leucocyte migration inhibition test were performed in 22 lepromatous, 10 non-lepromatous cases and 10 apparently healthy individuals who were all DNCB positive. Of these 2 lepromatous, 8 non-lepromatous cases and all the 10 apparently healthy individuals showed lepromin positivity. Average E-rosette counts (percentage) and mean leucocyte migratory index were significantly lower in lepromatous as compared to non-lepromatous cases.

Cell Migration Inhibition↗

PubMed1982

Immune status of subsided cases of tuberculoid (TT) and borderline tuberculoid (BT) leprosy.

A comparative study of lepromin reactions (early and late), M. leprae induced lymphocyte blastogenesis, per cent T Cell number in peripheral blood and immunoglobulin (IgG, IgA and IgM) levels have been made in TT-active, TT-subsided, BT-active and BT-subsided leprosy cases. No significant difference has been noted amongst these groups in the above mentioned investigations except in subsided BT cases where 9 out of 11 cases failed to evoke any late skin reaction to Dharmendra antigen. In addition, BT subsided cases also showed significantly raised levels of IgG. The significance of these findings with respect to their immunity and reinfection has been discussed.

Adolescent↗

PubMed1982

E--rosettes in leprosy patients.

Early and total E--rosettes counts were made in the leprosy patients of different clinical types classified histologically and compared with those of healthy controls. The T-cell population in LL cases were found to be significantly lower than in other types of leprosy cases and controls. The study of the E--rosette formation at different times of incubation indicated that any point of observation could be used for comparison. However, early (1 hour--2 hour) counts help to distinguish the LL cases from other types of leprosy. A good correlation was noticed between the percentage of rosettes and lepromin test.

Adolescent↗

PubMed1981

The in vivo and in vitro effects of levamisole in patients with lepromatous leprosy.

Levamisole, 150 mg daily, was administered on 2 consecutive days per week for 6 weeks to two groups of patients with lepromatous leprosy. Group I was composed of patients who were receiving specific anti-leprosy therapy for varying periods of time and Group II were untreated lepromatous patients. Whereas half the patients in Group I received levamisole and the other half a placebo, those in Group II all received levamisole. Patients in both groups showed a) no clinical improvement, b) no conversion of the lepromin reaction, c) no histological change in skin biopsies, d) conversion of SKSD skin reactions from negative to positive in 20% of patients from each group, and e) unaltered absolute neutrophil counts. Whereas the total lymphocyte counts were unchanged in patients from Group I, 13 patients from Group II showed an increased lymphocyte count of greater than 10%. Lymphocyte transformation and lymphokine production in the second group showed no significant change, although four patients showed some lymphokine production after levamisole therapy. E and EAC rosettes were significantly increased in cases where these were reduced prior to treatment with levamisole-Side effects due to levamisole were not experienced.

Adolescent↗

PubMed1980

Cutaneous responses to antigens and irritants in patients of leprosy.

Forty seven patients of various types of leprosy were skin tested with PPD, Dharmendra lepromin, DNCB, Coccidiodin, histamine and croton oil. Twenty five age matched normal controls were also included in the study. All types of leprosy patients reacted in smaller numbers and with decreased response to all antigens and irritants as compared to normal controls. Depression of response being minimum in tuberculoid and maximum in lepromatous group. None of the patients or controls reacted to coccidiodin. Details are given.

Adult↗