Lupus and leprosy: beyond the coincidence.

Systemic lupus erythematous (SLE) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. Disease flares have been mostly associated with parvovirus B19, cytomegalovirus, EBV and Mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ANA, anti nDNA and anti-ß2-GPI mainly in lepromatous leprosy. Mycobacterium leprae not only may determine symptoms that mimic lupus flares, including autoantibodies production, but could also act as a trigger for lupus reactivation; however, its association is still not fully explored. As demonstrated for tuberculosis, it is quite possible that molecular mimicry may also be involved in the interface of these two diseases. Some studies reported shared epitopes among idiotypes derived from 8E7 and TH9 lepromatous antibodies and those obtained from SLE patients, and it could partially explain the triggering phenomenon of SLE caused by M. leprae. We report and discuss three Brazilian patients whose disease was inactive and presented disease flares concurrently with the diagnosis of leprosy.

Autoantibodies in leprosy sera.

Our objective was to assess the prevalence of autoantibodies in patients with leprosy. Forty-one cases of lepromatous leprosy were studied. For the detection of autoantibodies we used the Elisa technique using the following purified antigens in an Elisa assay: dsDNA, ssDNA, histone, mitochondria, RNA, RNP, SS-A, SS-B, Sm, Scl-70, Anca C, Anca P and the cardiolipin complex. As a "cut off" point we used values shown on previous studies to differentiate normal from elevated values. Antibodies to SS-B, mitochondria and cardiolipin were the most prevalent in our study. Antimitochondrial antibodies distinct from those seen in primary biliary cirrhosis and antiphospholipid antibodies with variable ligand activity to B2GIP are frequent in the sera of leprosy patients.

Anticardiolipin antibodies in infections are heterogenous in their dependency on beta 2-glycoprotein I: analysis of anticardiolipin antibodies in leprosy.

We studied the effect of beta 2-GPI on binding of antibodies in sera from patients with leprosy and patients with the antiphospholipid syndrome (APS) to CL in enzyme-linked immunosorbent assays (ELISAs). Increased levels of IgG aCL were detected in 59 of 61 leprosy patients' sera by the standard aCL-ELISA in the presence of bovine beta 2-GPI and in 60 of the 61 leprosy patients' sera by the modified aCL-ELISA without beta 2-GPI. When tested by both aCL-ELISAs on the same plate, 10/31 leprosy sera and 9/10 APS sera bound better in the standard aCL-ELISA, 16/31 leprosy sera bound better in the modified aCL-ELISA and in five leprosy and one APS sera the difference was not significant. A dose-dependent enhancing effect of beta 2-GPI on the leprosy and APS sera binding to CL was confirmed using purified human beta 2-GPI. Enhanced binding was seen if beta 2-GPI was added either before or together with the test serum. In 11/61 leprosy sera increased levels of IgG antibodies against beta 2-GPI were found by ELISA. Leprosy anti-beta 2-GPI antibodies appear to be a separate antibody population recognizing only beta 2-GPI adsorbed on the ELISA plate. These results demonstrate heterogeneity of leprosy aCL with respect to their beta 2-GPI requirement for binding to CL.

Antimitochondrial (pyruvate dehydrogenase) antibodies in leprosy.

Sera from 69 patients with leprosy but without liver involvement were assayed for the presence of mitochondrial pyruvate dehydrogenase (PDH)-specific autoantibodies by enzyme-linked immunoabsorbent assay (ELISA), immunoblotting using PDH as an antigen and by enzymatic inhibition test. Twenty-seven of the leprosy serum samples (39.1%) were found to react with PDH by ELISA. However, unlike sera from primary biliary cirrhosis (PBC) patients, none of these were able to inhibit the PDH enzymatic activity. By immunoblotting, it was found that only 2 of the 27 positive sera recognized the 74-kD protein of the PDH complex, which is recognized by sera of most PBC patients. The antimitochondrial antibodies in lepra most probably recognize different epitopes than those in PBC. These findings may indicate that anti-PDH autoantibodies in patients with leprosy may arise by polyclonal B cell stimulation and may represent natural anti-PDH autoantibodies.