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.

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.