UC San Diego

Multiple sclerosis (MS) is an inflammatory autoimmune disease leading to myelin loss and axon damage. Studies have shown the complement to be a major player in MS damage, however no research has evaluated the novel role of the lectin mediated complement activation pathway in post-mortem brain tissue with MS. These presented studies have provided insight on the role of the lectin complement activation proteins in MS brain. Our analyses show an increased expression of mannose binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) in both the white matter and gray matter of MS brain compared to healthy controls. Co-localization of MBL with markers of axonal damage, neuroinflammation, and immune complexes suggests MBL and associated proteins may play an important role in the development of neuropathological characteristics of MS. Genetic variants of MBL2 and MASP-2 that lead to altered protein expression and function were not associated with the risk of the MS, however the small sample size did now provide high statistical power. Finally, Autoantibodies detected against MBL in the MS vs. non-MS healthy brain tissue may also lead to further tissue damage through antibody-dependent complement activation. Altogether, this study suggests that the lectin complement activation pathway could promote and prime aggressive immune response leading to brain tissue damage in MS and might be developed as a biomarker for MS. MBL based therapeutics could also be developed against MS related neuroinflammation and neurodegeneration