Chronic Inflammatory Demyelinating Polyneuropathy Due to the Administration of Pegylated Interferon .ALPHA.-2b: A Neuropathology Case Report

Abstract

We report a 35-year-old man who developed weakness in his extremities five months after pegylated interferon α (IFNα)-2b was administered. The serum tumor necrosis factor-α (TNFα) was elevated and nerve conduction studies revealed demyelination both in the distal and intermediate segments. The sural nerve pathology showed mild demyelinating process. The cessation of IFNα and administration of intravenous immunoglobulin improved both his clinical symptoms and the temporal dispersion in motor nerve conduction study. IFNα-induced CIDP is presumably a transient immunological condition that requires immunomodulatory therapy. The elevated serum TNFα may implicate the degree of downstream autoimmunitiy induced by IFNα.

Chronic inflammatory demyelinating polyneuropathy triggered by interferon‐α for chronic hepatitis B virus infection

“…However, this is not always the case, because some patients with IFN-induced CIDP were caused by pegylated form of interferon. 6,7 The present case provides evidence that IFN-a indeed triggers CIDP in association with HBV infection. Further investigation into the relationship between CIDP and IFN-a would be useful for a better understanding of the pathophysiology of CIDP.…”

“…We speculate that IFN‐α might trigger a pathological autoimmune reaction, such as molecular mimicry, in some immunologically‐predisposed patients, while suppressing pathological autoimmune activation . In the previous reports, CIDP associated with IFN‐α occurred in patients with HCV infection, except in a few cases with malignant melanoma . HCV infection is often associated with abnormal immunological responses, including peripheral neuropathy.…”

“…Therefore, that might be explained by that the pegylated IFN‐α2b stabilizing the plasma concentrations of interferon, preventing the occurrence of CIDP. However, this is not always the case, because some patients with IFN‐induced CIDP were caused by pegylated form of interferon …”

Deregulated Fcγ receptor expression in patients with CIDP

“… 21 A role for IFN-α in the pathogenesis of CIDP is less well established, although some studies report increased levels of type I IFN signaling in patients with CIDP 22 or development of CIDP associated with IFN-α therapy. 23 – 29 Activation of FcγRI on monocytes triggers differentiation into immature dendritic cells that induce autoreactive T cell responses and has therefore been implicated in mediating tissue injury in antibody-mediated autoimmune diseases. 30 FcγRI-mediated activation and differentiation of myeloid cells might also contribute to peripheral nerve damage in CIDP, where myeloid cells are believed to be the main local effector cells.…”

Toxic and drug-induced peripheral neuropathies

“…In animal models, overexpression of matrix metalloproteinases mediating myelin turnover and phenotypic remodeling of glial and neuronal cells, as well as secondary activation of inflammatory cascades, have been recently reviewed [21 & ]. TNFa blocking molecules and other immunomodulatory, immunosuppressive, or antineoplastic agents, widely used to treat several forms of inflammatory diseases, have been associated with dysimmune conditions, including various forms of demyelinating neuropathies [11,46,63,76]. dependent on accumulative dose or serum level) plays no identified role.…”