Querol L, Nogales-Gadea G, Rojas-Garcia R, et al.
Submitted by Andrew Tarulli, MD
About the Study
Immunocytochemical methods were used to identify antibodies to the paranodal protein neurofascin 155 (NF155) in 4 of 61 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). All of the patients had disabling (modified Rankin Scale scores of 4), predominantly distal weakness that was refractory to treatment with intravenous immunoglobulin (IVIg). Two of the patients were identified from a local sample of 53 patients with CIDP. The other 2 patients were from a national pool of 8 patients with previously-identified CIDP refractory to IVIg. Disabling tremor and ataxia was present in 3 of the 4 patients.
CIDP is readily diagnosed by finding a combination of proximal and distal weakness, nerve conduction studies showing acquired demyelination, and albuminocytological dissociation. There are, however, no biomarkers that predict response to therapy reliably: while most patients improve with intravenous immunoglobulin, a small subset remain refractory and need other immunosuppressive treatments. Identification of antibodies to components of peripheral nerve associated with specific phenotypes would be an important aid in optimizing treatment.
Querol and colleagues identified antibodies associated with NF155, a paranodal protein necessary for the formation of septate-like axo-glial junctions. Knockout of NF155 in mice produces a severe demyelinating polyneuropathy with prominent tremor and ataxia, similar to that seen in the patients in this study. The investigators noted that the NF155 antibodies were of the IgG4 isotype, which do not activate complement or bind to Ig Fc domain receptors, both of which are likely mechanisms of IVIg and thus, potential explanations for the lack of responsiveness to IVIg in this subset. Verification of the results of this study in other patients with CIDP, especially IVIg-refractory CIDP with tremor and ataxia is necessary.