Pathogenesis Of Chronic Inflammatory Demyelinating Polyneuropathy Research Articles

Mechanism and spectrum of anti‐glycolipid antibody‐mediated chronic inflammatory demyelinating polyneuropathy

AbstractThe pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP) is composed of cellular and humoral immunities. Macrophages might play a crucial role in cellular immunity. In addition, autoantibodies participate in the pathogenesis of CIDP. To date, various autoantibodies have been reported to affect peripheral nerve myelin. Although antibodies to glycolipids are frequently identified in Guillain‐Barré syndrome and closely related to the development of neuropathies, these are detected in only a small percentage of CIDP instances. Among glycolipids, sialosylneolactotetraosylceramide (LM1) is predominantly localized in human peripheral nerve myelin. LM1‐related antibodies (e.g. anti‐LM1, GM1/LM1 and GD1b/LM1 antibodies) are detected in some patients with CIDP and Guillain‐Barré syndrome. CIDP patients with those antibodies frequently present ataxia, but rarely have cranial nerve deficits; these features are associated with the localization of LM1, which is more abundant in the dorsal root than the cranial nerves. In immunoglobulin M paraproteinemic neuropathies, except for the anti‐myelin‐associated glycoprotein neuropathies, antibodies to glycolipids with disialosyl residues, such as GD1b and GQ1b, are also detected on occasion. Notably, this feature is clinically characterized by chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M paraprotein, cold agglutinins and disialosyl antibodies. Such clinical features are related to the localization of GD1b or GQ1b in human peripheral nerves. Overall, these correlations suggest a direct involvement of the antibodies in the pathogenesis of those aforementioned neuropathies.

IVIG regulates BAFF expression in patients with chronic inflammatory demyelinating polyneuropathy (CIDP)

Recent studies indicate that the cytokine B-cell activating factor (BAFF) is involved in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Intravenous immunoglobulin (IVIg) is standard treatment for CIDP and is known to rapidly modulate increased serum levels of pro-inflammatory cytokines. We evaluated the expression profile of BAFF and its corresponding BAFF-receptor in samples from CIDP patients, focusing on rapid changes before and after IVIg treatment. In CIDP patients BAFF serum concentrations were elevated compared to controls. Treatment with high-dose IVIg restored those elevated BAFF serum levels. Whereas treatment with IVIg did not affect BAFF production in monocytes, antibodies against BAFF could be detected in IVIg preparations, which may explain the short-term decrease of BAFF levels after IVIg treatment. Our data suggest that BAFF plays an important role in the pathogenesis of CIDP and may serve as marker for IVIg treatment response.

Prevalence and incidence rates of chronic inflammatory demyelinating polyneuropathy in the Japanese population

Objective and methods: To characterise the epidemiological features of chronic inflammatory demyelinating polyneuropathy (CIDP) in the Japanese population, this study performed a nationwide assessment of the prevalence and incidence rates...

Chronic inflammatory demyelinating polyneuropathy – update on pathogenesis, diagnostic criteria and therapy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable but possibly underdiagnosed disorder of the peripheral nerve. This review covers the growing literature of the past years that deals with the pathogenesis, diagnostic criteria and treatment of CIDP. The recent development of a biphasic animal model of experimental autoimmune neuritis may provide further insights into the pathogenesis of inflammatory demyelination of the peripheral nerve, such as in CIDP, and may allow the development of further innovative therapeutic strategies. In patients, the contribution of immune processes to the dysfunction in hereditary polyneuropathies and the association of hereditary neuropathy and CIDP has been described. Commonly used therapies remain corticosteroids, intravenous immunoglobulin and plasmapheresis; however, newer immunosuppressant approaches using mycophenolate mofetil or cyclosporin A, or immunomodulating therapies using monoclonal antibodies or interferons are presently under investigation. The growing body of knowledge on the pathogenesis of CIDP and further diagnostic differentiation of subforms may help to develop more-effective therapies for CIDP in the next few years.

Sural nerve T-cell receptor Vbeta gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy.

To investigate the utilization of T-cell receptor (TCR) variable (V) regions in infiltrates of sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy. The presence of infiltrating T lymphocytes in sural nerve biopsies may suggest a T cell-mediated immune mechanism in the pathogenesis of CIDP and vasculitic neuropathy. The utilization of TCR Vbeta regions in sural nerves of 13 patients with CIDP and five patients with vasculitic neuropathy was determined by immunohistochemistry, reverse-transcription PCR, and nucleotide sequence analysis. These techniques were also applied in four patients with chronic idiopathic axonal polyneuropathy (CIAP) who acted as noninflammatory controls, and in five autopsy controls. The TCR Vbeta utilization of infiltrating T cells in sural nerves of patients with CIDP, vasculitic neuropathy, and noninflammatory controls is heterogeneous. A dominant TCR Vbeta utilization was not found in any of the patients or controls. There is no evidence for the presence of clonally expanded T cells in sural nerves of patients with CIDP and vasculitic neuropathy.

Passive transfer of demyelination by serum or IgG from chronic inflammatory demyelinating polyneuropathy patients

Chronic inflammatory demyelinating polyneuropathy (CIDP) is regarded as an autoimmune disorder, but no clearly defined autoimmune mechanism has been described. Although most patients respond to plasma exchange, no convincing role for autoantibodies has yet been demonstrated. In this study, we have successfully passively transferred disease using sera and purified IgG from 4 of 12 patients responsive to plasma exchange by bypassing the blood-nerve barrier by intraneural injection or opening it by activated T cells. The sera from CIDP patients or purified IgG produced marked conduction block and demyelination, but normal sera or IgG or that from patients with multiple sclerosis or other neuropathies did not. These observations strongly support an important role for anti-myelin/Schwann cell autoantibodies in the pathogenesis of CIDP at least in some patients.