ANTIBODY TO MITOCHONDRIAL COMPLEX-I IN SOME PATIENTS WITH MULTIPLE SCLEROSIS

When pooled immunoglobulin G (IgG) from patients with multiple sclerosis (MS) was used to probe a human fetal spinal cord λgt 11 cDNA library, the IgG was found to bind to a predicted epitope of human mitochondrial ND4 sequence. To investigate the involvement of the ND4 as an autoantigen in MS, we determined the presence of specific antibody in the serum of MS patients and serum samples of some other autoimmune disease as controls. A peptide, which is part of the ND4 protein in human mitochondrial complex I, CysLeuAlaAsnSerAsnTyrGluArgThrHisSerArg, was conjugated with a maleimido-thiol bond to diphtheria toxoid and used as an autoantigen. To remove any IgG which bound to diphtheria toxoid and the bovine serum albumin (BSA) blocking agent in the ELISA, the sera were preadsorbed before being incubated with the conjugate. About 20% of patients with multiple sclerosis (MS) had antibody to the peptide and when present, the level was found to fluctuate. In preliminary experiments autoantibody to ND4 was found to be not specifically associated with MS. The prevalence and involvement of the autoantibody in multiple sclerosis remains to be determined.