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PubMedDate not supplied

Immunomodulation with corticosteroids and levamisole in leprosy as gauged by in vivo lepromin and in vitro CMI responses.

Corticosteroids and Levamisole are known to be immuno suppressive and immuno stimulating agents respectively. Their effects on polar types of leprosy, tuberculoid and lepromatous have been studied using in vivo lepromin and in vitro lymphocyte count, rosette formation, L.T.T. and L.M.I.T. parameters. Immunosuppressive effect of corticosteroids on tuberculoid leprosy is marked with reduced and negative lepromin sensitivity but same does not hold true with other in vitro C.M.I. tests. Similar results are obtained with levamisole exhibiting its ineffectiveness in lepromin conversion in lepromatous cases although some improvement is observed in other in vitro C.M.I. tests. Evaluation of the results showed: lack of correlation between in vivo lepromin and in vitro other C.M.I. parameters with corticosteroids and levamisole lepromin sensitivity has some unknown influence other than thymic factors, prolonged corticosteroid therapy may produce permanent immunosuppression in tuberculoid cases making them more vulnerable towards lepromatous pole and lepromin sensitivity is more reliable, stable and easy to perform.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Studies on lepromin and soluble antigens of M.leprae: their classification standardization and use.

Before the discovery of armadillo as a susceptible animal the source of M.leprae was limited and hence the use of lepromin was not common in the field. In recent times, the soluble antigens of armadillo-derived M.leprae have been used extensively in the field. Although the results of the study show that these antigens do not differentiate always a susceptible form from the resistant form, they are able to segregate the polar forms of leprosy. In a given field situation the criteria for diagnosis is so stressed that leprosy is overdiagnosed and within one year of follow up nearly half the number of cases are noted as not leprosy. Hence, in such situations lepromin reaction would be definitely a poor correlate with the type of leprosy. However, in hospital based studies the lepromin reaction has always been and would remain useful in confirming the classification (Sengupta et al 1984). Lepromins and M.leprae soluble antigens have gone through extensive standardization procedures. As these antigens contain mostly common mycobacterial antigens along with the M.leprae-specific antigens, these antigens are unable to specifically diagnose M.leprae infection. After purification of M.leprae from infected armadillo tissue, it was expected that the soluble antigen of M.leprae would probably be as useful as tuberculin. However, this was not found to be true in case of lepromin. Specificity for M.leprae has been noted in the epitopes (antigenic sites) on cross reacting molecules (12 kd, 18 kd, 28 kd, 35 kd, 36 kd) of mycobacteria (Ivanyi et al 1983; Watson 1989). These specific epitopes, if synthesized, could be of use as skin test antigens for determining M.leprae infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Bacterial↗

PubMedDate not supplied

Immuno-epidemiological studies on subclinical infection in leprosy. III. Yearly observations and follow-up studies of schoolchildren by using FLA-ABS and lepromin tests.

The schoolchildren in three regions of Miyako Islands, Okinawa Prefecture, were surveyed annually, from 1978 to 1984, by using the fluorescent leprosy antibody absorption (FLA-ABS) test and the lepromin reaction with the Dharmendra's antigen, for detecting the individuals at high risk of leprosy and for evaluating predictive value of these immunological tests. Constant potency of these tests was confirmed by the percentage of positive reactions among the children in the first grade of elementary schools (5 or 6 years old) surveyed from 1980 to 1984. A temporal rise or drop of the percentages during this period seemed to associate with the yearly reported number of new leprosy cases in each region. Among 1,168 schoolchildren tested with FLA-ABS once or twice or more, the percentage of positive reactions was significantly higher in the children with the enlargement of peripheral nerve without sensory loss than in those without this signs and symptoms. The longer the duration of this signs and symptoms, the higher the percentage of positive FLA-ABS tests. Lepromin test did not show any significant correlation with this signs and symptoms. A concordant persistence or change between the FLA-ABS tests and neural signs or symptoms was observed in 133 out of 331 children examined twice or more. Discordant changes in the remaining were mainly attributed to a conversion to seronegativity before the disappearance of neural signs and symptoms. Changes of FLA-ABS and lepromin reactivities between the initial and final tests suggested a spontaneous cure of subclinical infection with Mycobacterium leprae among the children who were FLA-ABS positive but lepromin negative at the initial test and therefore considered to be a group at high risk of leprosy. Although neural signs and symptoms were found in the majority of these children, none of them so far developed overt symptom of the disease. Based on these findings, predictive value of FLA-ABS test together with lepromin was discussed.

Age Factors↗

PubMed1990

Lymphocyte blastogenesis and lepromin reactivity in leprosy patients and their parents.

To determine whether there is an inherited familiar trait linked to the lymphocyte blastogenesis test (LTT), under stimulation with PHA, lepromin and Mycobacterium leprae in culture medium containing autologous plasma, this test was carried out in patients with the polar forms of leprosy and their parents. The lepromin reaction was also studied in the patients and their parents because, since the test is negative in lepromatous (L) patients and a greater proportion of negativity is detected among their relatives, it might be assumed that the lymphocytes of these individuals could have a lower tendency towards blastogenesis than lymphocytes of tuberculoid (T) patients and their relatives. Thirty individuals were studied, ten of them being leprosy patients (4 L and 6 T) and the remaining their parents; 115 LTT, including control and stimulated cultures, were performed. In the limited number of patients and parents studied, the results showed that mothers of either L or T patients displayed a similarly low response to the stimulants M. leprae and lepromin. The lepromin reaction was negative in all L patients and positive in 3 out of 8 parents, as well in all the T cases and their fathers. Fathers and their T descendants were lepromin positive and there was a certain relationship between this reactivity and blastogenesis. This might suggest a possible inherited familiar trait related to a relative degree of resistance. However, further evidences from studies with larger number of subjects are required to support this hypothesis.

Female↗

PubMed1973

Late lepromin reaction in untreated patients with indeterminate leprosy under 21 years old in Burma.

Studies on lepromin reactivity in indeterminate (I) leprosy have usually been carried out among patients in whom the disease appeared 1 or more years before testing. This may result in misleading findings because a high proportion of patients, probably those showing moderate or strong lepromin reactions, seem to progress to the tuberculoid pole of leprosy in a relatively short time (<1 year), and in many the lesions heal spontaneously. The object of the present study was to determine the frequency and intensity of late lepromin reactions (macroscopic readings) in untreated I patients aged under 21 years who had had the disease for less than 1 year. Of 209 patients tested with lepromin containing 160 x 10(6) bacilli/ml only a small proportion ( not equal 7%) showed a negative or doubtful lepromin reaction, while 61.5% were 2+ and 3+ reactors. These findings indicate that a favourable outcome may be expected in most I cases in the trial area.

Adult↗

PubMed1993

Appearance of gamma delta T cell receptor-positive cells following alpha beta T cell receptor-positive cells in the lepromin reaction of human skin.

To elucidate the involvement of human gamma delta T cell receptor (TcR)+ cells in mycobacterial infection, we examined the kinetics of these cells in skin lesions of human lepromin reaction. The majority of CD3+ cells two days after induction of the lepromin reaction were alpha beta TcR+, while gamma delta TcR+ cells accounted for only 4.4 +/- 1.4% of the CD3+ cells. On day 21, the incidence of gamma delta TcR+ cells was greater (16.0 +/- 2.1%), although alpha beta TcR+ cells remained the predominant population. These kinetics of alpha beta TcR+ cells and gamma delta TcR+ cells contradict the 'early response, self-surveillance' hypothesis for gamma delta TcR+ cells in mice. Most of the gamma delta TcR+ cells in this study of the lepromin reaction were V delta 1- V delta 2+ V delta 9+, and some of them proliferated in the skin lesions, suggesting that gamma delta TcR+ cells in the lesions may respond to mycobacterial antigens and may play an active part in the lepromin reaction. However, these gamma delta TcR+ cells were not correlated with granuloma formation, the size of necrotic areas, mycobacterial content, or the incidence of CD4+ cells and CD8+ cells.

Fluorescent Antibody Technique↗

PubMed2000

Comparative study of Mitsuda reaction to nude mouse and armadillo lepromin preparations using nine-banded armadillos.

In 14 nine-banded armadillos the Mitsuda response to nude mouse-derived lepromin (lepromin-nu/nu) was compared to that of armadillo-derived lepromin (lepromin-A) by injecting the reagents intradermally into either side of the abdomen of the animal and examining the biopsies from the sites after 12 days. The histopathologic responses to both antigens were found to be similar, whether the animal was Mitsuda-negative (lepromatous) or Mitsuda-positive (tuberculoid). It is pointed out that armadillos are good experimental models for leprosy, and their use can replace humans in experimental studies.

Animals↗

PubMed1987

Lepromin-induced lymphoproliferative response of experimental leprosy monkeys: regulatory role of monocyte and lymphocyte subsets.

We investigated the immunological status of seven normal, control Mangabey monkeys and 23 Mangabey monkeys experimentally inoculated with Mangabey-origin Mycobacterium leprae. Clinically, these monkeys were divided into three broad groups: a recently inoculated group, a resistant group, and a susceptible group. The resistant group included 11 monkeys, seven of which showed no clinical sign of disease to date and four of which had shown local disease that partially regressed spontaneously. The susceptible group included eight monkeys, five of which have disseminated disease and three with local but stable disease. When peripheral blood mononuclear cells of these monkeys were cultured with Dharmendra-type human lepromin, one of seven normal monkeys, four of four of the recently inoculated group, seven of 10 resistant monkeys, and three of eight susceptible monkeys showed significant responses. In this experimental monkey model, we studied possible regulatory mechanisms by using OKT4- and OKT8-enriched lymphocytes, and Fc receptor-positive (FcR+) and FcR- monocyte (M phi) subsets. The OKT4+ subset was the main lepromin-responsive cell type. High percentages of OKT8+ cells showed a good negative correlation with the lymphoproliferative responses of T-enriched cells supplemented with unfractionated M phi. But the depletion of OKT8+ cells could not increase the response of nonresponding monkeys' lymphocytes. The resistant group and susceptible group did not differ in their percentages of OKT8+ cells. Because OKT8+ cells negatively regulate the response of lymphocytes and OKT4+ cells are the main responding cells, OKT8+ cells are phenotypically and functionally suppressor cells and OKT4+ cells are the helper/inducer cell population in this system. The FcR- M phi population mainly includes antigen-presenting activity, but high percentages of FcR- M phi showed a significant negative correlation with lymphoproliferative responses in the resistant group. A weak but significant lymphocyte response to Dharmendra lepromin was obtained by depleting FcR+ M phi from cultures of some susceptible monkeys, whereas lymphocytes of other susceptible monkeys remained unresponsive to lepromin. By these criteria, we could find an array of immunological defects in monkeys with experimental leprosy. The data suggest that some immunological defects may exist in the OKT4+ lymphocytes or FcR- M phi of leprosy monkeys.

Animals↗

PubMed1979

Recommended safety requirements for the preparation of lepromin: a WHO Memorandum.

The need for standardizing the preparation of lepromin and establishing safety requirements for it was recognized by the Scientific Working Group on the Immunology of Leprosy (IMMLEP) and its Steering Committee in 1978. It has now recommended the preparation of standard integral (Mitsuda-type) lepromin and, in collaboration with the WHO Biologicals unit, has drafted requirements for its preparation and testing. These direct that the source material should be Mycobacterium leprae from biopsy specimens of skin obtained from human (lepromatous) tissues or from the tissues of armadillos infected with M. leprae. The procedures to be followed for processing and testing the source material and for the preparation of lepromin from it are described. Requirements are laid down for the safety testing and labelling of the final product. In future, IMMLEP will consider supporting only those projects involving the use of lepromin prepared in accordance with these regulations.

Humans↗

PubMedDate not supplied

In situ characterization of cells in the dermal infiltrates of lepromin reaction using monoclonal antibodies.

A study was made on the in situ characteristics of dermal infiltrates in the early and late lepromin reaction with monoclonal antibodies defining T cell subsets, Langerhan cells and Ia like antigens. The early reaction (24 hrs) was elicited either with standard Dharmendra lepromin or leprosin-A and the late reaction (3-4 weeks) was elicited with standard Dharmendra lepromin. In all, 15 biopsies were studied. Most lymphocytes in the infiltrates of both the lepromin and leprosin reactions were positive for OKT 11, Leu 3a, OKT 8 and Ia like antigens indicating thereby the presence of activated T cells. A high proportion of OKT6 + cells were also noticed in the infiltrates of these reactions. In the late reaction, the lymphocytes in the granulomas were predominantly activated T lymphocytes expressing OKT 11, Leu 3a, OKT 8 and Ia like antigens. Leu 3a + cells were scattered diffusely amidst the epithelioid cells. In contrast, OKT 8 + cells were present mainly in the peripheral region of the granuloma. A small proportion of OKT6 + cells were also seen in these granulomas. Ia like antigens and T6 antigens were not discernible on the epithelioid cells. No difference in the number of OKT6 + epidermal langerhan cells was observed in the various types of reactions.

Antibodies, Monoclonal↗

PubMedDate not supplied

[Correlation between early (Fernandez) and late (Mitsuda) reactions in non-contact children and adolescents without manifestations of leprosy, tested with human lepromin and different concentrations of armadillo antigen in 3 double-blind trials].

The authors carried out 3 double blind trials to determine the correlation between the early and the late lepromin reactions and to verify the practical and control values of the 48 hours or Fernandez reaction. Children and adolescents non-contacts were tested with human lepromin (40 x 10(6) bacilli/ml) and different concentrations of armadillo lepromin (160, 40, 20, 10, 5, 2,5, and 1 x 10(6) bacilli/ml). The conclusions are as follows: 1. The coefficients of correlation (r values) point out that the correlation between the two reactions is poor or almost null. 2. The negative or doubtful reactions, the most often observed, have no practical value because they are almost always followed by a positive Mitsuda reaction. 3. The positive Fernandez reaction was always followed by a positive Mitsuda reaction. Thus it has practical importance. However as the frequency of early positivity is low with human and armadillo lepromin of lower concentrations, recommended in routine testing, the 48 hours reading is unnecessary and without control value. It would represent a loss of time and money.

Adolescent↗

PubMed1982

Double blind trial on the effect of certain soluble cytoplasmic mycobacterial antigens on the late reactivity to lepromin.

Two hundred forty-four children between six months and 59 months of age from nursery schools and playgrounds in Ribeirão Preto, São Paulo, Brazil, were randomly allocated into five groups. These received: 1) intradermal BCG; 2) placebo; 3) antigen F, containing soluble cytoplasmic components of the mycobacteria Mycobacterium tuberculosis, M. aquae, and M. lepraemurium; 4) antigen G, containing soluble cytoplasmic components of M. piscium, and M. balnei, and 5) antigen H, containing soluble cytoplasmic components of M. leprae. BCG preinjected children had the highest proportion of positive late lepromin reactions. The injection of antigens F, G, or H had no effect on the late lepromin reactions. These findings contrasted with those observed in our earlier trial in which the injection of antigens X (containing soluble cytoplasmic components of the mycobacteria M. avium and M. gallinarum), Y (M. simiae, M. gallinarum, and M. avium), and Z (M. leprae, M. simiae, and M. borstelense) had caused significantly lower positive late lepromin reactions. By comparing the data of the present investigation with the findings of the first trial, it appears that the antigens obtained from M. borstelense and from either M. avium or M. gallinarum could have been instrumental in the impairment of lepromin activity observed in the first trial.

Antigens, Bacterial↗

PubMed1981

Assessment of Dharmendra antigen. (IV) Antigenic analysis of lepromins.

In order to pinpoint the active portion of the skin antigens including Dharmendra and other lepromins, a study was carried out by subjecting the antigens to electrophoretic and immunoelectrophoretic analysis. These analyses identified two components, anionic and cationic, in lepromin sonicates. The anionic component was stainable with a protein strain, whereas cationic component formed precipitin arcs on immunoelectrophoresis with sera from lepromatous leprosy patients. BCG sonicate could also be resolved into two similar components. The cationic component of BCG apparently a glycoprotein, cross reacted with cationic component of lepromin and also showed a reaction of identity in gel diffusion. The specificity of anionic (proteinaceous) component of lepromin remains to be established.

Anions↗

PubMed1993

Lepromin skin testing in the classification of Hansen's disease in the United States.

Hansen's disease, or leprosy, although a relatively uncommon disease in the United States, continues to be important because of its implications--physical, psychological, and social--for the patient. Prognosis and treatment of the disease are based largely on clinical classification, which ranges from the multibacillary "lepromatous" to the paucibacillary "tuberculoid" forms, depending on the patient's specific immune capabilities. Traditionally, skin testing with lepromins--suspensions of the etiologic agent of Hansen's disease, Mycobacterium leprae--have been used as adjuncts to clinical parameters for classification in endemic areas. However, these have not been systematically studied in the United States. This report describes the results obtained from skin testing 38 volunteers (22 patients and 16 uninfected persons) with standard lepromin preparations. These results support the adjunctive value of lepromins for clinically classifying Hansen's disease in our "hypoendemic" population.

Animals↗

PubMed1975

Impairment of reactivity to lepromin by mycobacterial antigens related to, or identical with, Mycobacterium leprae.

Three hundred and twenty young children were injected with Bacillus Calmette-Guerin (BCG) saline, or with one of the mycobacterial cytoplasmic antigens related with Mycobacterium leprae. At an appropriate time thereafter they were tested for dermal hypersensitivity to the antigens and for reactions to lepromin. Whereas all the antigens induced cell-mediated immunity, the incidence and intensity of late response to lepromin were significantly reduced in children preinjected with the cytoplasmic mycobacterial antigens, as contrasted with increased lepromin reactivity in the BCG group and with the findings in saline-injected children.

Antigens, Bacterial↗

PubMed1990

Positive Mitsuda lepromin reactions in long-term treated lepromatous leprosy.

Twenty-four lepromatous (LL) patients, treated for 22 to 40 years with chemotherapy, including sulphones and with multidrug therapy, were tested with standard Wade-Mitsuda lepromin. Thirteen gave weak positive (3-4 mm) Mitsuda reactions, confirmed histologically in the ten whose reactions were biopsied. Six of the eleven negative reactors were partly accounted for by a history of relapse, and two others had probably taken dapsone irregularly. Eleven control LL patients, treated for less than 20 years, were uniformly lepromin negative. Spontaneous lepromin conversion appears to occur around 24 years after commencing successful chemotherapy. The late Mitsuda conversions are attributed to delayed clearance of the reservoir of bacterial antigen, but a poor correlation between Mitsuda and Fernandez positivity is not explained.

Humans↗

PubMed2000

Experience and lessons from the use of lepromin and Mycobacterium leprae-specific serology.

Skin testing with lepromin, which produces a delayed-type hypersensitivity reaction, has been used in the classification of leprosy, and a good correlation has been found between immunological status and the reaction to lepromin. In addition, the prognostic value of the lepromin test has been demonstrated. More recently, skin testing with two soluble antigens of Mycobacterium leprae showed no difference of the mean size of the reaction between household contacts and non-contacts, indicating that these antigens are not useful for the diagnosis of leprosy. This and other evidence points to the need for a better skin test antigen capable of detecting infection of individuals by M. leprae. Whereas serological assays for antibodies against both PGL-1 and the 35 kDa antigen of M. leprae have been found to yield positive results in 90-100% of patients with lepromatous (BL/LL) leprosy, these assays fail to identify 40-60% of patients with tuberculoid (BT/TT) leprosy, because of the presence of only an insignificant level of antibody against components of M. leprae in these patients' serum, although, in many BT patients, antibody signal could be detected in the local lesions. These data indicate that there remains a need for a specific diagnostic test for leprosy.

Humans↗

PubMed1979

Lepromin-induced suppressor cells in patients with leprosy.

The possibility of an active mechanism of immunologic suppression in leprosy was explored by assessing the in vitro lymphocyte responses of 61 leprosy patients and 30 normal individuals to the mitogen Con A in the presence or absence of Dharmendra lepromin. Lepromin-induced suppression of Con A stimulation was found in 32 of 35 lepromatous patients and 15 of 15 borderline patients, but only 2 of 15 tuberculoid patients and 2 of 30 normal controls. Cell fractionation studies indicated at least two cell populations involved in the in vitro lepromin-induced suppressor activity, adherent cells and T gamma-cells.

Cell Adhesion↗