myelin-basic-protein and Leprosy

Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs. Further, probable role of molecular mimicry in nerve damage of LPs was investigated. We observed significantly high level of anti-MBP antibodies in LPs across the spectrum and a positive significant correlation between the level of anti-MBP antibodies and the number of nerves involved in LPs. We report here that 4 B cell epitopes of myelin A1 and Mycobacterium leprae proteins, 50S ribosomal L2 and lysyl tRNA synthetase are cross-reactive. Further, M. leprae sonicated antigen hyperimmunization was responsible for induction of autoantibody response in mice which could be adoptively transferred to naive mice. For the first time our findings suggest the role of molecular mimicry in nerve damage in leprosy.

Topics: Animals; Demyelinating Diseases; Humans; Leprosy; Lysine-tRNA Ligase; Mice; Mice, Inbred BALB C; Molecular Mimicry; Mycobacterium leprae; Myelin Basic Protein; Rabbits; Ribosomal Proteins

The nerve biopsies of 11 patients with pure neuritic leprosy were submitted to routine diagnostic procedures and immunoperoxidase staining with antibodies against axonal (neurofilament, nerve growth factor receptor (NGFr), and protein gene product (PGP) 9.5) and Schwann cell (myelin basic protein, S-100 protein, and NGFr) markers. Two pairs of non-adjacent histological cross-sections of the peripheral nerve were removed for quantification. All the fascicles of the nerve were examined with a 10X-ocular and 40X-objective lens. The immunohistochemistry results were compared to the results of semithin section analysis and clinical and electroneuromyographic data. Neurofilament staining was reduced in 100% of the neuritic biopsies. NGFr positivity was also reduced in 81.8%, PGP staining in 100% of the affected nerves, S100 positivity in 90.9%, and myelin basic protein immunoreactivity in 90.9%. Hypoesthesia was associated with decreased NGFr (81.8%) and PGP staining (90.9%). Reduced potential amplitudes (electroneuromyographic data) were found to be associated with reduced PGP 9.5 (63.6%) and nerve fiber neurofilament staining (45.4%) by immunohistochemistry and with loss of myelinated fibers (100%) by semithin section analysis. On the other hand, the small fibers (immunoreactive dots) seen amid inflammatory cells continued to be present even after 40% of the larger myelinated fibers had disappeared. The present study shows an in-depth view of the destructive effects of leprosy upon the expression of neural markers and the integrity of nerve fiber. The association of these structural changes with the clinical and electroneuromyographic manifestations of leprosy peripheral neuropathy was also discussed.

Topics: Adult; Antigens, Bacterial; Biomarkers; Biopsy; DNA, Bacterial; Electromyography; Female; Glycolipids; Humans; Immunoenzyme Techniques; Immunohistochemistry; Leprosy; Male; Mycobacterium leprae; Myelin Basic Protein; Nerve Fibers, Myelinated; Nerve Tissue Proteins; Neuritis; Neurofilament Proteins; Polymerase Chain Reaction; Receptors, Nerve Growth Factor; S100 Proteins

Topics: Antibodies; Humans; Leprosy; Myelin Basic Protein; Peripheral Nervous System Diseases

Topics: Animals; Cattle; Dose-Response Relationship, Immunologic; Humans; Leprosy; Lymphocyte Activation; Myelin Basic Protein; Myelin P2 Protein; Myelin Proteins; Sciatic Nerve