Genetic and Immunologic etiology of chronic recurrent multifocal osteomylitis (CRMO)

University Of Iowa, Iowa City IA

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Abstract

? DESCRIPTION (provided by applicant): Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory disease that affects the bone, skin and joints, and can permanently deform the skeleton. Clinically, CRMO is difficult to recognize and cannot be detected via biomarkers, so diagnosis is often delayed. Although CRMO is rare, affected patients often have a personal or family history of inflammatory conditions (e.g., psoriasis, inflammatory bowel disease, or inflammatory arthritis), so these diseases likely arise from dysregulation of the same immunologic pathway. We recently identified mutations in FBLIM1 (Filamin binding protein-1) in individuals with non-syndromic CRMO and psoriasis, and discovered altered FBLIM1 expression in the Pstpip2 deficient mouse model of CRMO. Using protein immunoprecipitation mass spectroscopy (IP-MS) we identified novel binding partners of Pstpip2, the critical protein in the pathogenesis of CRMO in mice. We hypothesize that Pstpip2-interacting proteins are involved in bone homeostasis and that the genes that encode them are candidates for non-syndromic CRMO. Our goals for this proposal are to determine how mutations in FBLIM1 lead to CRMO and psoriasis; to determine the physiologic function of novel PSTPIP2 binding partners in inflammation of the bone and skin and to test if these proteins are associated with CRMO pathogenesis in our human cohort. The long term goal is to translate this newly acquired knowledge to the design of new therapeutic strategies so that it is translated into the care of individuals with CRMO and its associated disorders including psoriasis, inflammatory bowel disease and inflammatory arthritis.