Loss of Schwann cell plasticity in chronic inflammatory demyelinating polyneuropathy (CIDP)

Abstract

BackgroundChronic inflammatory demyelinating polyneuropathy (CIDP) is often associated with chronic disability, which can be accounted to incomplete regeneration of injured axons. We hypothesized that Schwann cell support for regenerating axons may be altered in CIDP, which may account for the poor clinical recovery seen in many patients.MethodsWe exposed human and rodent Schwann cells to sera from CIDP patients and controls. In a model of chronic nerve denervation, we transplanted these conditioned Schwann cells intraneurally and assessed their capacity to support axonal regeneration by electrophysiology and morphometry.ResultsCIDP-conditioned Schwann cells were less growth supportive for regenerating axons as compared to Schwann cells exposed to control sera. The loss of Schwann cell support was associated with lower levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in CIDP sera and correlated with altered expression of c-Jun and p57kip2 in Schwann cells. The inactivation of these regulatory factors resulted in an altered expression of neurotrophins including BDNF, GDNF, and NGF in CIDP-conditioned Schwann cells in vitro.ConclusionsOur study provides evidence that pro-regenerative functions of Schwann cells are affected in CIDP. It thereby offers a possible explanation for the clinical observation that in many CIDP patients recovery is incomplete despite sufficient immunosuppressive treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0711-7) contains supplementary material, which is available to authorized users.

Pathological spontaneous activity as a prognostic marker in chronic inflammatory demyelinating polyneuropathy

“…Therefore, neuroprotection and regeneration should be a further goal in the development of new treatment options in CIDP. Recently, it has been demonstrated that Schwann cells cultured with sera from CIDP patients support regenerating axons less effectively than Schwann cells conditioned with control sera due to a lower expression of granulocyte‐macrophage colony‐stimulating factor and other neurotrophins [16]. Furthermore, intrathecally applied steroids seem to have a protective role against oxidative stress in Schwann cells [17].…”

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP

“…Recently, it has been demonstrated that CIDP patients show a diminished pro-regenerative function of Schwann cells leading to the axonal loss and therefore incomplete clinical recovery after treatment which is probably caused by inflammatory mediators [ 25 ]. Thus, differences in immune responses between typical and atypical CIDP we have demonstrated might also influence Schwann cell function resulting in different treatment responses and long-term outcome.…”

Schwann Cell Plasticity in Peripheral Nerve Regeneration after Injury

“…The rate of nerve regeneration is approximately 1 mm/day, depending on the site of the lesion and on the patient age. SC plasticity diminishes with age, showing an altered expression of c-Jun [111] and a weak regenerative capacity [112,113].…”