Characterisation of Autoantibodies to Peripheral Myelin Protein 22 in Patients With Hereditary and Acquired Neuropathies

Abstract

To investigate the possibility that an autoimmune mechanism may play a role in the hereditary neuropathy Charcot‐Marie‐Tooth type 1A (CMT1A), sera were analysed by Western blot for anti‐peripheral myelin protein 22 (PMP22) autoantibodies. These sera were compared with sera from patients with CMT type 2 (CMT2), acquired peripheral neuropathies such as chronic inflammatory demyelinating neuropathy (CIDP), anti‐MAG IgM neuropathy, Miller‐Fisher syndrome (MFS), diabetic neuropathy and with control blood donors. Anti‐PMP22 positive sera were detected in 70% of patients with CMT1 and unexpectedly in 60% of patients with CMT2. Interestingly, 44% of the patients with other peripheral neuropathies and 23% of the apparently healthy controls showed also anti‐PMP22 antibody reactivity. Immunohistochemical analysis of the human anti‐PMP22 antisera on healthy sural nerve sections and on PMP22‐expressing COS cells revealed that these sera did not recognize endogenous PMP22. Our results indicate that anti‐PMP22 autoantibodies are found in sera of patients with different types of peripheral neuropathies, but their role in the pathogenesis of these diseases remains to be determined.

Immunological study of hereditary motor and sensory neuropathy type 1a (HMSN1a)

“…36 37 Antibodies against PMP22 were more common in patients with HMSN1a than in normal subjects, but not more than in those with other neuropathies. These results are similar to those of Ritz et al 13 As no clinical differences were detected between those with anti-PMP22 antibodies and those without, it seems unlikely that clinical phenotypic differences can be ascribed to a humoral response directed towards PMP22. It is possible that the finding of anti-PMP22 antibodies in HMSN1a is usually a non-specific reaction to nerve damage rather than of primary pathological importance.…”

“…12 Recently, using different techniques, a high proportion of patients with different types of peripheral neuropathy including HMSN were found to have anti-PMP22 antibodies. 13 Ten patients had antibodies against PMP22 detected by both ELISA and western blot. Of these, six also had antibodies against a 30 kDa protein, likely to represent antibodies against P0, which have been described in other peripheral neuropathies.…”

“…12 Using a different assay others have detected anti-PMP22 antibodies in 70% of patients with HMSN1a and 60% with HMSN2 as well as in those with other neuropathies. 13 We have now studied 55 patients with HMSN1a to establish whether immunological mechanisms might contribute to the phenotypic heterogeneity of this group.…”

Chronic inflammatory demyelinating polyneuropathy as an autoimmune disease

“…The presence of autoantibodies against myelin antigens supports the hypothesis that CIDP is an AD (Table 5) [27,[119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135]. The presence of complement and immunoglobulin on the surface of Schwann cells in the sural nerve has been described in CIDP [136,137].…”

Advances in understanding and treatment of immune‐mediated disorders of the peripheral nervous system

“…280 Antibodies to various myelin antigens have been studied extensively. 65,148,222 Nevertheless, evidence for a pathogenetic role of antibodies in CIDP is strong for anti-P0 antibodies only in certain subgroups.…”