Humoral Immune Response

Marinos C. Dalakas, M.D., Principal Author

For more than 20 years, it has been acknowledged that autoantibodies contribute to the pathogenesis of CIDP, due to the discovery of immunoglobulin and complement deposition on myelinated nerve fibers and the presence of IgG bands in cerebrospinal fluid. (Dalakas, 1980)

Passive transfer experiments have demonstrated that serum or purified IgG from a small number of patients with CIDP induces conduction block and demyelination in rat nerves with the 28-kD myelin protein zero being identified as one of the putative target antigens. (Yan, 2000). Passive transfer of CIDP IgG prolongs NCV in marmoset monkeys (Heininger, 1984).

Other target antigens may be gangliosides and/or related glycolipids. In a few patients with CIDP, serologic evidence shows recent infection with Campylobacter jejuni. Given the shared expression of carbohydrate epitopes in nerve glycolipids and microbial lipopolysaccharides, this finding may hint at molecular mimicry as the underlying cause of CIDP in rare cases. (Melendez-Vasquez, 1997) The best example of molecular mimicry in CIDP is when the disease is rarely associated with melanoma because several carbohydrate epitopes are shared by the myelin sheath and the melanoma. (Weiss,1998)

In a small study of 46 patients with CIDP, 12 patients had serum reactivity against presumably nonmyelin antigens on Schwann cells. (Kwa, 2003)

A role for complement, autoantibodies or and immune complexes in CIDP is also supported by the presence of complement activation products in peripheral nerve or plasma and deposition of IgM, IgG and C3 of some patients (Dalakas 1980, 1982; Nyland, 1981; Koski,1985, 1990)

Demyelination and conduction block may also result from serum constituents such as cytokines, complement, or other inflammatory mediators (e.g., nitric oxide). The low frequency of specific antibodies seen in patients with CIDP may imply that various antibodies and separate mechanisms are involved in individual patients.