αB-Crystallin immunolocalization yields new insights into inclusion body myositis

Objective: To study the expression of the small heat shock protein, αB-crystallin (αBC), in inclusion body myositis (IBM). Background: In humans, αBC is constitutively expressed in the eye lens, muscle, and heart, but not in lymphoid tissues. Induced expression of αBC occurs under metabolic stress, in virus-infected lymphocytes, and in degenerative brain lesions, including neurofibrillary tangles and senile plaques in AD. The previously reported pathologic similarities between AD and IBM prompted us to study αBC expression in IBM. Methods: Immunolocalization of αBC in muscle of 11 patients with IBM, 50 patients with other muscle diseases, and 4 controls; and quantitative analysis of the frequency of fibers with 1) increased αBC expression in IBM and polymyositis and 2) structural abnormality (vacuolated, non-necrotic and invaded by mononuclear cells, Congo red–positive, SMI-31 positive, and ubiquitin positive) in IBM. Results: We detected enhanced expression of αBC not only in all structurally abnormal IBM fibers, but also, and with severalfold higher frequency, in IBM fibers without significant structural abnormality (X fibers) (p values in paired t-tests < 0.001). We also found enhanced αBC in abnormal fibers in other diseases; X fibers, however, were extremely sparse or absent, except in two atypical cases of polymyositis refractory to immunotherapy. Conclusion: That the X fibers are much more frequent than the structurally abnormal fibers in IBM points to a pathogenic stressor acting upstream to the development of structural abnormalities. The identification of this stressor is now of paramount importance for deciphering the enigma of IBM.

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