1. Figure 3 Current model of immunopathogenesis in CIDP
Figure 3 | Current model of immunopathogenesis in CIDP. The immune response in chronic inflammatory demyelinating polyneuropathy (CIDP) involves cellular and humoral immune responses. Antigen-presenting cells (APCs), such as dendritic cells or macrophages, activate autoreactive T cells. These T cells can cross the blood–nerve barrier (BNB) to enter the peripheral nerve, a process mediated in part by chemokines, cellular adhesion molecules and metalloproteinases (orange circles). In addition, T cells can activate B lymphocytes via secretion of cytokines, such as IL-4 and IL-6. Within the PNS, T cells are re-exposed to the target antigen by local APCs (a macrophage is depicted), thereby reactivating these cells and driving clonal expansion within the peripheral nerve. CD4+ T cells can differentiated into T-helper 1 (TH1) cells, which, once activated by APCs, release pro-inflammatory cytokines and drive the inflammatory process, or TH2 cells, which control and mitigate inflammation by secreting anti-inflammatory mediators. Macrophages are predominantly activated by TH1 cells, and exhibit increased phagocytic activity, produce cytokines and release toxic mediators, such as nitric oxide, that can directly damage Schwann cells and contribute to axonal damage. In addition, pro-inflammatory cytokines, such as tumour necrosis factor (TNF) or IFNγ, are locally produced by B cells, and contribute to demyelination and axonal damage. Antibodies can mediate demyelination by antibody-dependent cellular cytotoxicity, can block epitopes that are functionally relevant to nerve conduction, and can activate the complement system via the classical pathway, yielding pro-inflammatory mediators and the lytic C5b–9 terminal complex. Termination of the inflammatory response is mediated, in part, by macrophages through induction of T-cell apoptosis and release of anti-inflammatory cytokines, such as IL-10 and transforming growth factor (TGF)-β. Myelin proteins, such as P0, P2, myelin basic protein (MBP), myelin-associated glycoprotein (MAG), connexin 32 (Cx32) and glucagon-like peptide (GLP), are putative target antigens in CIDP.
Rajabally, Y. A. et al. (2017) CIDP and other inflammatory neuropathies in diabetes — diagnosis and management
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