Abstract

Terminal complement complex deposition in endomysial capillaries detected by a C5b-9 immunostain is considered a diagnostic feature for dermatomyositis. However, we found widespread microvascular C5b-9 reactivity in a substantial subset of muscle biopsies with denervation changes, and in nerve biopsies of peripheral neuropathies, particularly in patients with diabetes. It is unclear whether the presence of C5b-9 deposition signifies active immune-mediated vascular injury that requires immune suppression therapy. We retrospectively identified 63 nerve biopsies in patients with a documented history of diabetes, 26 of which had concomitant muscle biopsies, as well as 54 control nerve biopsies in patients without a documented diabetes history, 18 of which had concomitant muscle biopsies. C5b-9 immunostain was performed on all cases. 87% of the nerve biopsies and 92% of the muscle biopsies from diabetic patients showed microvascular C5b-9 reactivity, compared to 34% and 50% in non-diabetic patients. The differences were statistically significant (p < 0.0001 for nerve and p = 0.002 for muscle). The C5b-9 reactivity was generally proportional to the extent of microvascular sclerosis in diabetic patients, but unrelated to inflammation or vasculitis. C5b-9 deposition in micro-vasculature in both muscle and nerve is therefore a common feature in patients with diabetic neuropathies and may have diagnostic utility. Precaution needs to be taken before using muscle capillary C5b-9 reactivity as evidence of myositis.

Highlights

  • C5b-9, known as the terminal complement complex (TCC) or membrane attack complex (MAC), is a multimer derived from five complement components that mediates the cell killing effects of the complement cascade

  • Diffuse and strong endoneurial microvascular C5b-9 reactivity is associated with microvascular sclerosis in diabetic patients, but not associated with inflammation We examined whether endoneurial microvascular C5b-9 deposition was associated with active vasculitis or Unknown Diabetic status (Total)

  • In this study we showed that widespread microvascular deposition of C5b-9 in both muscle and nerve was characteristic of diabetic patients with peripheral neuropathy, with a combined sensitivity of 88.4% and specificity of 83.3% for the diabetic status when using 1+ as cut off

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Summary

Introduction

C5b-9, known as the terminal complement complex (TCC) or membrane attack complex (MAC), is a multimer derived from five complement components that mediates the cell killing effects of the complement cascade. Yell et al Acta Neuropathologica Communications (2018) 6:11 diffuse C5b-9 deposition in both muscle endomysial capillaries and nerve endoneurial vessels. Microvascular C5b-9 deposition in both peripheral nerve and muscle has only been described in neuropathy with pipe-stem capillaries [13], dermatomyositis-associated sensory neuropathy [10], and neuropathy with serum anti-TS-HDS antibody [11]. These are rare, controversial entities only described in isolated case reports. Muscle endomysial capillary C5b-9 deposition has not been described in diabetic patients

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