Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune mediated radiculo-neuropathies (IMRN) has not been previously described.

METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for IgG antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein, Caspr1) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury.

RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with CIDP, 4 with ventral root radiculopathies (VRR) and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination. Three patients (12.7 %) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis respectively.

CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype. This article is protected by copyright. All rights reserved.