Parkinson hastalığında ve Multiple System Atrophy'de otoimmün antikor düşüşü; immünoterapik stratejilere doğru bir adım.

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

BackgroundParkinson's' disease (PD) and Multiple System Atrophy (MSA) are progressive brain disorders characterized by intracellular accumulations of α-synuclein and nerve cell loss in specific brain areas. This loss causes problems with movement, balance and/or autonomic functions. Naturally occurring autoantibodies (NAbs) play potentially an important role in clearing or/and blocking circulating pathological proteins. Little is known about the functional properties of anti-α-synuclein NAbs in PD and MSA, and there have been opposing reports regarding their plasma concentrations in these disorders.MethodsWe have investigated the apparent affinity of anti-α-synuclein NAbs in plasma samples from 46 PD patients, 18 MSA patients and 41 controls using competitive enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) set-ups.ResultsWe found that the occurrence of high affinity anti-α-synuclein NAbs in plasma from PD patients is reduced compared to healthy controls, and nearly absent in plasma from MSA patients. Also, levels of α-synuclein/NAbs immunocomplexes is substantially reduced in plasma from both patient groups. Further, cross binding of anti-α-synuclein NAbs with β- and γ-synuclein monomers suggest, the high affinity anti-α-synuclein plasma component, seen in healthy individuals, is directed mainly against C-terminal epitopes. Furthermore, we also observed reduced occurrence of high affinity anti-phosphorylated-α-synuclein NAbs in plasma from PD and MSA patients.ConclusionsOne interpretation implies that these patients may have impaired ability to clear and/or block the effects of pathological α-synuclein due to insufficient/absent concentration of NAbs and as such provides a rationale for testing immune-based therapeutic strategies directed against pathological α-synuclein. Following this interpretation, we can hypothesize that high affinity autoantibodies efficiently bind and clear potentially pathological species of α-synuclein in healthy brain, and that this mechanism is impaired or absent in PD and MSA patients.

İlgili konular