Immunological study of hereditary motor and sensory neuropathy type 1a (HMSN1a)
- 1Department of Neuroimmunology, Guy's King's and St Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, London SE1 9RT, UK
- 2Institute of Neurology, University College, London, UK
- Correspondence to: Professor R A C Hughes, Department of Neuroimmunology, Guy's King's and St Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, London SE1 1UL, UK;
- Received 20 March 2001
- Accepted 23 October 2001
- Revised 3 September 2001
Objectives: Fifty three patients were studied to investigate whether autoimmune or inflammatory mechanisms could explain the phenotypic heterogeneity of patients with hereditary motor and sensory neuropathy type 1a (HMSN1a). Methods: Serum samples were examined for antibodies to peripheral nerve myelin protein 22 (PMP22), ganglioside GM1 and cauda equina homogenate, and interleukin-6 (IL-6) and soluble tumour necrosis factor receptor 1 (sTNF R1) concentrations. Serological results were compared with those from patients with other neuropathies (ONPs, n=30) and with normal subjects (n=51).
Results: In the group as a whole, no relation emerged between clinical severity and any immune parameters. Immunohistochemical examination of four sural nerve biopsies did not show significant inflammatory infiltration. In a subset of 12 patients who experienced stepwise progression of disease, there was a trend towards a higher proportion having anti-PMP22 antibodies (33% v 15% of those with gradual disease progression, 3% ONPs, and no normal controls) and complement fixing antibodies to human cauda equina (25% v 5% with gradual progression, 8.6% ONPs, 3.9% normal controls, p=0.07).
Conclusions: Patients with HMSN1a and a stepwise disease progression may have an inflammatory, autoimmune component superimposed on the genetic condition.
- HMSN1a, hereditary motor and sensory neuropathy type 1a; PMP22, peripheral nerve myelin protein 22; IL-6, interleukin-6; sTNF R1, soluble tumour necrosis factor receptor 1; ONPs, other neuropathies; EAN, experimental autoimmune neuritis; GBS, Guillain-Barré syndrome; CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; NDS, neurological disability score; GNDS, Guy's neurological disability score; CMAP, compound motor action potentials; SNAPs, sensory nerve action potentials; NCVs, nerve conduction velocities; ECD1 and ECD2, first and second extracellular domain peptides; AIDP, acute inflammatory demyelinating polyradiculoneuropathy; IDP, inflammatory demyelinating polyradiculoneuropathy; DAB, 3,3'