The mechanism of disease of CIDP is complex and not fully understood1,2
The disease mechanisms of chronic inflammatory demyelinating polyneuropathy (CIDP) are complex and likely vary between patient groups. At its core, the autoimmune attack in CIDP involves the targeting and stripping away of the protective myelin sheath of the peripheral nerve axon, resulting in the disruption of its ability to transmit signals properly. The result is slowed nerve conduction and signal blockages that manifest as muscle weakness and sensory changes.1,3,4
Research suggests 3 interconnected immune components work together to cause demyelination and nerve damage2
Cellular immunity2,5,6
- Activated T-cells and macrophages infiltrate peripheral nerves
- Macrophages strip and phagocytose compact myelin, while pro-inflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-2) increase blood-nerve barrier permeability, driving further immune cell recruitment
Humoral immunity2,3,5
- Immunoglobulin G and immunoglobulin M autoantibodies deposit on Schwann cells and myelin
- These antibodies may drive demyelination by triggering macrophage phagocytosis via fragment crystallizable receptors and activating the complement cascade
Complement immunity7,8
It's thought that...
- Autoantibodies bound to the myelin trigger the complement pathway
- Complement overactivation generates opsonins, anaphylatoxins that amplify inflammation, and membrane attack complex assembly that damages myelin
References: 1. Allen JA. Neurol Ther. 2020;9(1):43-54. doi:10.1007/s40120-020-00184-6 2. Di Stefano V, Barbone F, Ferrante C, et al. Eur J Inflamm. 2020;18:1-17. doi:10.1177/2058739220942340 3. Quast I, Keller CW, Hiepe F, Tackenberg B, Lünemann JD. Ann Clin Transl Neurol. 2016;3(9):730-735. doi:10.1002/acn3.331 4. Bus SRM, Broers MC, Lucke IM, et al. J Neurol. 2022;269:945-955. doi:10.1007/s00415-021-10677-5 5. Wolbert J, Cheng MI, Meyer zu Horste G, Su MA. JCI Insight. 2020;5(3):e132411. doi:10.1172/jci.insight.132411 6. Mathey EK, Pollard JD, Armati PJ. J Neurol Sci. 1999;163:47-52. doi:10.1016/S0022-510X(99)00009-X 7. Rumsey JW, Lorance C, Jackson M, et al. Adv Therap. 2022;5:2200030. doi:10.1002/adtp.202200030 8. Querol LA, Hartung HP, Lewis RA, et al. Neurotherapeutics. 2022;19(3):864-873. doi:10.1007/s13311-022-01221-y