Type 1 Diabetes-Associated Autoantibodies, Sera and T-Cell Receptor Sequences Recognize Myelin Basic Protein: A Novel Peripheral Diabetic Neuropathy-Multiple Sclerosis Connection.

(1) Background: Neuropathies are common complications of type 1 diabetes (T1D) and previous research demonstrated concomitant demyelinization involving myelin basic protein (MBP). T1D patients have a significantly increased risk of multiple sclerosis (MS) and vice versa. The causes are unknown. (2) Methods: Proteonomic searches using BLAST were used to identify similarities between T-cell receptor (TCR) sequences from T1D and MS patients. LALIGN was used to explore whether T1D-related proteins mimic MBP. Enzyme-linked immunoadsorption assay (ELISA) was used to test for cross-reactivity between T1D-related antibodies or sera with MBP. Ultraviolet spectroscopy was used to test whether T1D-specific T-cell receptor (TCR) sequences recognized MBP. (3) Results: BLAST revealed that a subset of T1D and MS TCR are nearly identical. Sequence similarities were found by LALIGN between MBP and T1D-associated antigens. Antibodies against insulin, PTPRN(IA-2), and GAD1 recognized MBP. Most TCR sequences derived from T1D patients recognized MBP as an antigen. Most T1D-derived sera recognize MBP, but healthy sera do not. BLAST revealed that coxsackievirus proteins do not mimic MBP, but many Clostridia proteins do. (4) Conclusions: Cross-reactivity between TID-related antibodies and TCR with MBP may help to explain the pathogenesis of T1D neuropathies and the increased co-occurrence of these two diseases.