Reduction of a subpopulation of T lymphocytes in lepromatous leprosy

A reduction in number of a subpopulation of T lymphocytes was noted in lepromatous leprosy cases with high bacillary load. Tuberculoid and treated lepromatous patients, who were bacillary negative had normal levels of these cells. B-cell numbers were high in lepromatous patients irrespective of treatment and bacillary load.     

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.     

Elimination of mycobacterium leprae subsequent to local in vivo activation of macrophages in lepromatous leprosy by other mycobacteria

This investigation studied the possibility of activating lepromatous macrophages by a local `in vivo' test.     

Isolation and analysis of circulating immune complexes in leprosy

Circulating immune complexes (CIC) were isolated by two antigen nonspecific methods from 60 leprosy patients belonging to borderline tuberculoid (BT) and lepromatous (LL) types with and without reactions. CIC were elevated in both BT and LL reactions. CIC from BT in reaction (BTR) were found to consist largely of IgG and C3, whereas, C-reactive protein could be found in CIC from LL reactions (LR). In addition, IgM and rheumatoid factor were demonstrated in the complexes of LR patients who had mainly arthritis. Antimycobacterial antibody was seen in the complexes of two-thirds of LR patients who had predominantly skin manifestations as part of their reaction. The relevance of these findings to the clinical manifestations of different types of reactions is discussed.     

Immune complex cryoglobulinaemia in lepromatous leprosy: a pathogenetic approach to some clinical features of leprosy

Cryoglobulins isolated from the sera of six patients with lepromatous leprosy were extensively studied by various immunochemical techniques.

Immunoelectrophoresis and analytical ultracentrifugation revealed in all cases the presence of two components only, which were identified as IgG and IgM respectively. The IgG component of all six cryoprecipitates and the IgM component of five of them were polyclonal, whereas the remaining IgM component was monoclonal as it produced a narrow-banded electrophoretic spike and contained kappa light chains only.

Anti-γ-globulin activity, detected in all sera and isolated cryoglobulins, was consistently found to be associated with the IgM fraction of the mixed cryoglobulins and was present at very high titres in the IgM monoclonal component. β_1A serum levels were decreased in all cases.

The cryoglobulins that appear to be immune complexes of the IgG/anti-IgG type may play a role in the pathogenesis of some clinical features of leprosy patients.

     

Nodular lepromatous leprosy: Report of a case diagnosed by FNA

Lepromatous leprosy can present with skin nodules which can be misdiagnosed as soft tissue tumors or infected cysts. FNA can be diagnostic of unstained, refractile, intracellular mycobacteria are recognized on Romanowsky stained smears. File stain for Mycobacterium leprae confirms the diagnosis. Awareness of the differential diagnosis of skin nodules yielding foamy histiocytes on FNA, briefly discussed, should help avoid error. Diagn Cytopathol 1994; 11:373–375. © 1994 Wiley-Liss, Inc.     

Evidence for the presence of M. leprae reactive T lymphocytes in patients with lepromatous leprosy.

Evidence for the presence of Mycobacterium leprae reactive T cells in many lepromatous leprosy (LL) patients was obtained using in vitro antigen-induced lymphoproliferative responses. (1) Co-cultures of T enriched cells from LL patients when combined with 2 h adherent cells (AC) from HLA-D compatible tuberculoid leprosy individuals showed significant levels of 3H-thymidine incorporation in the presence of soluble and integral M. leprae antigens. (2) More interestingly, autologous T cell + AC co-cultures also showed significant improvement in antigen-induced lymphoproliferation in nine of 16 lepromatous patients. Insignificant improvement was observed in similar co-cultures of tuberculoid leprosy patients. (3) Addition of exogenous, purified human interleukin-2 (IL-2) to antigen stimulated PBMC from some lepromatous patients showed the best improvement in terms of overall 3H-thymidine incorporation, indicating that lepromatous patients possess T cells which can differentiate to an IL-2 responsive state. Significantly, the level of proliferation varied within the group. A proportion of clinically similar lepromatous patients failed to show improvement by any of the above methods.     

Nongranulomatous involvement of the bone marrow in lepromatous leprosy

Bone marrow involvement in lepromatous leprosy has been characterized histologically by a proliferation of foamy histiocytes containing lepra bacilli, the so-called Virchow cells. The authors have studied three patients with biopsy-proven lepromatous leprosy in whom Fite stain, performed on histologic sections of bone marrow aspirates, demonstrated numerous bacilli lying free in the interstitium in the absence of Virchow cells or focal collections of foamy macrophages. Two of the patients had a recent diagnosis of lepromatous leprosy by skin biopsy; the third patient had a 33-year history of lepromatous leprosy that had been treated. Bone marrow aspirates were performed in all three patients for evaluation of anemia. The findings indicate that the bone marrow may act as a reservoir for viable organisms in the absence of a host response in treated and untreated patients with lepromatous leprosy. The persistence of viable organisms in the bone marrow in patients with lepromatous leprosy may account for the high rate of relapse and/or recrudescence of the disease following cessation of specific therapy. Bone marrow examination with the Fite modification of the acid-fast stain is therefore indicated in such patients to evaluate bone marrow involvement and the efficacy of treatment.     

Characterization of circulating immune complexes in heart disease

Circulating immune complexes (CIC) were characterized for the content in IgG, IgA, IgM, C3 and C4 in patients with heart disease. The levels of IgG, IgM and C4 in PEG-precipitates of patients' sera were significantly higher than those found in controls, and the precipitation profile was similar to that of rheumatoid arthritis patients. Differences were observed in the composition of CIC: IgM was highest in association with myocarditis, and C3 predominated in cases of valvular disease. Complex-bound C4 was significantly higher in patients with myocardial infarction which developed pericarditis either early or late in the evolution of the disorder. Antimyocardial antibodies could be detected in sera and in corresponding PEG-precipitates. The bulk of the data suggests that CIC might play a pathogenetic role in various heart diseases.     

Disseminated sporotrichosis in a patient with a past history of lepromatous leprosy: a case report

Disseminated sporotrichosis is uncommon and usually occurs in patients who are immunodeficient. Here we describe a male patient who was otherwise in good physical condition, who presented with disseminated sporotrichosis. The only significant event in his past medical history was lepromatous leprosy which had been treated 42 years earlier.     

Suppressor response in lepromatous leprosy patients: role of Leu 2a cells.

The contribution of non-specific suppressor mechanisms to the overall immunoregulatory defect observed in lepromatous leprosy was evaluated. Con A-induced suppression was assayed using the standard two-stage test in 27 lepromatous leprosy patients, 19 of them during the quiescent stage (LL) and eight during erythema nodosum lepromatosum (ENL). Lymphocytes from normal individuals react in this assay, yielding higher suppression as the numbers of Con A-induced suppressor cells (Leu 2a+ cells) increase. In contrast, two patterns of response were observed in both LL and ENL patients: those giving lower suppression as the number of suppressor cells increased (LL-A and ENL-A) and those responding with the normal pattern (LL-B and ENL-B). The abnormal dose-response profile was not related to the disease stage, as both ENL and LL patients were included in groups with normal or atypical response. Reaction of the potential suppressor cells with anti-Leu 2a antibody abolished suppression in LL-B and normals, whereas Con A-induced suppression was unchanged or higher in ENL-A, ENL-B and LL-A, indicating that in these patients Leu 2a+ cells interfered with the generation of Con A-induced suppression. The contribution of spontaneous suppression was examined and it was shown that suppressor activity in the absence of Con A stimulus was higher in ENL (both ENL-A and ENL-B) and LL-A. Thus, it appears that the occurrence of high spontaneous suppressor activity, probably related to in vivo activation, is associated with a relative inability to generate de novo suppression after Con A stimulation in these patients.     

Chemotherapy of lepromatous leprosy: Recent developments and prospects for the future

Leprosy is a major debilitating infectious disease, primarily of the developing world. In this paper the current status and future prospects of antimicrobial therapy of the severe anergic lepromatous form of the disease are reviewed. Until the last few years only dapsone, rifampicin, clofazimine and ethionamide have had practical application in its therapy, and only rifampicin was bactericidal. Recently, antibiotics from three different classes have been found to be bactericidal in lepromatous patients: a tetracycline (minocycline), a macrolide (clarithromycin), and several fluoroquinolones (including pefloxacin, ofloxacin and sparfloxacin). Against a background of drug resistance and bacterial persistence, recommendations for multidrug therapy and the means to devise rationally based therapy for the future are discussed.     

Defect in the generation of cytotoxic T cells in lepromatous leprosy.

Cytotoxic T cells are consistently produced in normal individuals after in vitro stimulation by a pool of mitomycin-treated normal lymphocytes. Patients suffering from lepromatous leprosy (LL), presenting with large amounts of Mycobacterium leprae and without a history of erythema nodosum leprosum (ENL) are unable to generate such cytotoxic T cells, while lepromatous patients with ENL which, in the present study were all deprived of M. leprae, react normally.     

Characterization of a factor in leprosy serum that inhibits the growth of mitogen-stimulated normal human lymphocytes.

A factor that inhibits the growth of mitogen-stimulated lymphocytes from normal donors has been detected in the sera of patients with chronic leprosy. The inhibitory activity was detected with similar frequency in patients with tuberculoid or lepromatous leprosy, although higher levels of activity were detected in the latter. The factor reduced the growth in volume of the lymphocytes in the first 24 hr after stimulation, the synthesis of RNA during the first 3 days of culture and the replication of DNA in 72-hr cultures. All the inhibitory activity co-purified with IgG on gel filtration, ammonium sulphate fractionation and ion exchange chromatography. The activity was stable to heating at 56 degrees but labile at 100 degrees and was absorbed from serum or from purified IgG preparations by staphylococcal protein A. On gel filtration of the sera on Sephadex G-200, none of the activity appeared in the void volume, indicating that it is not due to immune complexes. We conclude that the activity is due to an IgG antibody and suggest that it is an autoantibody since the sera inhibited the growth of all donor lymphocytes tested.