Abstract & Commentary
Source: Mahad DJ, et al. Expression of chemokines in cerebrospinal fluid and serum of patients with chronic inflammatory demyelinating polyneuropathy. J Neurol Neurosurg Psychiatry. 2002;73:320-323.
No single antigen has yet been identified as the target in all patients with chronic inflammatory demyelinating polyneuropathy (CIDP), a presumed autoimmune disorder similar to chronic experimental allergic neuritis, where both humoral and cell-mediated immune responses have been documented. Evidence suggests that specific chemokines play a role in pathogenesis.
Chemokines, cytokines that attract mononuclear cells to sites of inflammation, are divided into 4 families of which the majority are designated a and b chemokines, the former recruiting predominantly T lymphocytes, the latter T lymphocytes and monocytes. Serum and cerebrospinal fluid (CSF) levels were quantified in 9 CIDP patients, and compared to 10 benign headache and 10 nondemyelinating neuropathy (NDN) controls, to determine the presence of an association, if any, between CIDP and chemokines. a chemokines CXCL9 and CXCL10 and b chemokines CCL2, CCL3, and CCL5 were assayed using the ELISA method. Kruskal-Wallis and Mann-Whitney tests were used for statistical analysis.
CSF concentrations of CXCL9 and CXCL10 (a chemokines) were significantly elevated in CIDP patients (P < 0.001) compared to headache and NDN controls. CXCL9 was higher in serum than in CSF in 7 of 8 CIDP patients, and CXCL10 was higher in CSF than in serum in 6 of 9 CIDP patients. b chemokine CCL3, but not CCL2 or CCL5, was significantly elevated (P = 0.043) in the CIDP group compared to controls. CIDP patients with or without relapse or previous treatment did not demonstrate differential patterns of chemokine expression in the serum or CSF. Also, no correlation was found between chemokine levels and CSF protein. a chemokines CXCL9 and CXCL10 and b chemokine CCL3 may be involved in the pathogenesis of CIDP and may prove to be future targets in its treatment.
Commentary
Sural nerve biopsies from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (n = 10 each), and noninflammatory neuropathy controls (n = 8) were examined to determine the chemokine receptor expression pattern of their inflammatory infiltrates (Brain. 2002;125:823-834). Endoneurial macrophages expressed CCR-1 and CCR-5, while invading T lymphocytes expressed CCR-2, CCR-4 and CXCR-3. CXCR-3 was the receptor expressed in the highest numbers by invading T cells compared to other receptors. This suggeted that it might have a specific role in chemokine-mediated lymphocyte ingress into inflamed nerve. Using the Kruskal-Wallis and Mann-Whitney U-tests, interferon-g-inducible protein (IP-10), a CXCR-3 ligand, was significantly increased (p < 0.05) in GBS and CIDP cerebrospinal fluid. In situ hybridization revealed that IP-10 mRNA was abundantly expressed in GBS inflamed perineurial vessels, probably in association with endothelial cells. Monokine induced by interferon-g (Mig) did not differ among the patients and controls. Specific chemokine receptors and IP-10 appear to play a pathogenic role in inflammatory demyelinating neuropathy. —Michael Rubin
Dr. Rubin, Professor of Clinical Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.
No single antigen has yet been identified as the target in all patients with chronic inflammatory demyelinating polyneuropathy, a presumed autoimmune disorder similar to chronic experimental allergic neuritis, where both humoral and cell-mediated immune responses have been documented. Evidence suggests that specific chemokines play a role in pathogenesis.
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