Specificity of lymphocytotoxic autoantibodies (LCAbs) found in the serum of leprosy patients: class I MHC antigens.

Lymphocytotoxic autoantibodies (LCAbs) of the IgM class have been identified in patients with borderline tuberculoid (BT) and borderline lepromatous (BL) leprosy with Type I reactions (I) as well as lepromatous leprosy (LL) patients with erythema nodosum leprosum reactions (ENL). The observation that lymphocytotoxic activity (LCA) was reduced in the presence of platelets led us to determine whether LCAbs had specificities for Class I Major Histocompatibility Complex (MHC) determinants. Absorption of LCA positive sera with platelets, classically used to deplete Class I specific lymphocytotoxic antibodies, reduced LCA towards autologous as well as allogeneic target cells. This was true for LCA positive sera from all patient classifications (group BT in the autologous system, p less than 0.01; in all other patient groups, p less than 0.001). Introducing B-2m to cytotoxicity assays only marginally reduced LCA when added at high concentrations (5 mg/ml). An anti-Class I MHC antiserum which blocked the lytic activity. The data indicate that LCAbs while absorbed by platelets, are not specific for the Class I MHC antigens. The autoantigen recognized by these autoantibodies therefore remains to be identified.

Changes in epidemiological indices following the introduction of WHO MDT into the Guyana leprosy control programme.

In December 1981 the multidrug regimen recommended by the WHO Study Group of October 1981, was introduced into the Guyana Hansen's Disease Programme. This paper examines the changes that occurred in epidemiological indices over the 6 years following the introduction of MDT and also evaluates changing work loads and staffing patterns.

Serum lymphocytotoxic activity in leprosy.

Sera from 167 patients across the spectrum of leprosy and 46 endemic controls were screened for lymphocytotoxic activity (LCA). The Terasaki microdroplet lymphocytotoxicity assay was performed at 37 degrees C and 15 degrees C to test sera for LCA against a panel of lymphocytes from 50 donors which represented most known HLA-ABC antigens. Raised complement-dependent LCA at 15 degrees C was seen in leprosy patients with histories of erythema nodosum leprosum (ENL) or reversal/Type I (I) reactions. Eighty-six per cent of lepromatous (LL) patients with a history of ENL (n = 21, P less than 0.001), 83% of borderline lepromatous (BL) and 88% of borderline tuberculoid patients (BT) with a history of Type I reactions (n = 12, P less than 0.01 and n = 24, P less than 0.001 respectively) had LCA compared to 39% of endemic controls (n = 46). LCA was attributed to IgM on the basis of reduced activity when serum was treated with both dithiothreitol or absorbed with antiserum for IgM. Removal of immune complexes and rheumatoid factor did not influence LCA. LCA-positive sera reacted similarly with allogeneic lymphocytes from either healthy donors or leprosy patients. Moreover LCA-positive sera reacted with autologous lymphocytes. Specificities for HLA-ABC antigens were not identified. The potential role of these autoantibodies, manifested in leprosy patients with hypersensitivity reactions remains speculative.

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.

Integrated leprosy control in Guyana.

Guyana instituted a "find and treat" leprosy program in 1971 that made use of existing out-patient facilities and staff. The program, based on an integrated domiciliary approach to diagnosis, treatment, and examination of contacts, has proved successful. This article describes development of the program and discusses the prospects for control and eventual eradication of leprosy in Guyana.