Autoantibodies to post-translationally modified type I and II collagen in Charcot Neuroarthropathy in subjects with Type 2 Diabetes Mellitus

AIMS: Charcot Neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is unknown yet. In autoinflammatory diseases, as rheumatoid arthritis, characterized by inflammation and joints involvement, autoantibodies against post-translationally modified (ox-PTM) collagen type I (CI) and Type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in CN, investigating the presence of autoantibodies ox-PTM-CI and -CII, in subjects with CN. METHODS: In this case-control study, we enrolled 124 subjects with type 2 diabetes mellitus (47 with CN, 37 with diabetic peripheral neuropathy without CN, and 40 withuncomplicated diabetes), and 32 healthy controls. CI and CII were modified with ribose and other oxidant species and the modifications were evaluated with SDS-PAGE. Binding of sera from the subjects were analyzed with ELISA. RESULTS: Age, body mass index, waist and hip circumferences, and lipid profile were similar across the four groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidative-modified forms of CII was found in subjects with CN and DN. Conversely, for CI, an aspecific increased reactivity was noted. CONCLUSIONS: Our results detected the presence of autoantibodies against oxidative posttranslational modified collagen, particularly CII, in subjects with CN and DN, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of CN.