Diffuse microvascular C5b-9 deposition is a common feature in muscle and nerve biopsies from diabetic patients

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.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0512-6) contains supplementary material, which is available to authorized users.

Edematous myositis: a clinical presentation first suggesting dermatomyositis diagnosis

“…Furthermore, there was no difference observed in comparison to DM without limb edema. Nevertheless, C5b-9 deposits are not a sufficient sign to make the diagnosis of DM (5,7,31,36) and three cases (3-4,6) did not respond to any specific DM characteristic. This suggests that limb edema can be seen as a symptom of IIM and that it will mainly concern patients suffering from a DM.…”

Distinct tissue injury patterns in juvenile dermatomyositis auto-antibody subgroups

“…Capillary C5b-9 expression is a characteristic finding in dermatomyositis [24]. Although it is not completely specific and have also been reported in muscles from diabetic patients with poor glycemic control [28] and myopathy with anti-SRP autoantibody [29]. The distribution of C5b-9 positive capillaries is more concentrated in the perifascicular region in dermatomyositis, but more diffuse/random in the latter two conditions.…”

“…Several lines of evidence, however, challenge this hypothesis. First, widespread C5b-9 deposition in capillaries is a very common finding in the muscle and nerve of patients with poorly controlled diabetes [28,32]. However, with the exception of localized diabetic muscle infarction, myofiber necrosis in these patients is rare and they nearly never develop perifascicular atrophy or other morphological features of inflammatory myopathy.…”

Treatable, motor‐sensory, axonal neuropathies with C5b‐9 complement on endoneurial microvessels

“…Although there are many descriptions of neuropathies associated with epineurial vessel damage, there is less information about clinical syndromes associated with immune disorders of endoneurial microvessels 9‐11 . In this study we report a series of patients with clinical motor‐sensory neuropathy syndromes with progressive, asymmetric, and predominantly distal involvement and electrodiagnostic testing showing axon loss 12 without demyelination 13 .…”