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    • In this issue of describe their work

    2018-10-30

    In this issue of , describe their work on 51 patients with CIDP from 2 centres, investigated for the pro-inflammatory protein MSRV-Env (Multiple Sclerosis Associated Retroviral element), encoded by the Human Endogenous Retrovirus HERV-W. MSRV-Env had been previously detected in a small number of patients with CIDP used as neurological controls in a study of patients with multiple sclerosis (MS). A heterogeneous group of patients with other neurological diseases as well as healthy blood donors was used as controls. Detailed clinical description was not available although the majority (24 subjects) had symmetrical sensory and motor deficits, 9 had Lewis–Sumner syndrome (LSS) and one pure sensory CIDP, of unspecified subtype. Nearly half received immunoglobulins, one in six was on immunosuppressants and over a quarter, were untreated, although their disease activity status was not specified. Mean disease duration was 7years with however, a very wide range of 9weeks up to 42years. MSRV-Env expressions were found significantly higher in CIDP patients than in healthy blood donors and, of note, inversely correlating with disease duration. The expression was not high in neurological controls. IL6 and CXCL10 chemokine levels were both significantly higher in CIDP than in all controls, this being for the former, a contradictory finding in comparison to previous studies. MSRV-Env expression was raised in 5/7 sural nerve biopsies from CIDP patients but in neither of 2 control biopsies. In a further experiment, the authors found that the pro-inflammatory effects of MSRV-Env on human Schwann buy PF-01367338 as measured by IL6 and CXCL10 concentrations, were inhibited by the humanized IgG4 subclass monoclonal antibody, GNbAC1. They concluded that the autoimmune reaction in CIDP may result from TLR4-driven activation of innate immunity by MSRV-Env protein, making it a possible therapeutic target and raising the possibility that GNbAC1 may represent a potential innovative treatment for CIDP. This is already the focus of phase II trials in MS (). These findings are interesting with conceivable implications for future CIDP research. One of the main issues with the study, partly acknowledged, is that of small numbers. Furthermore, the breakdown per CIDP subtype is imprecise, and leaves still lesser numbers which prevents any meaningful analysis per subgroup. This is however of paramount importance as different CIDP subtypes may have varying underlying pathophysiology, the disorder representing a spectrum of related conditions rather than an entity (). Although thought to be both implicated, relative contributions of T-cell and antibody-mediated mechanisms are uncertain. It has been suggested that Lewis–Sumner syndrome for instance may involve cellular immunity as opposed to typical CIDP which may instead relate to antibody-mediated mechanisms (). As a result, it is possible that Lewis–Sumner syndrome may be less responsive to main CIDP therapies (). In recent years, studies on antibody specificity in CIDP have focused on the node of Ranvier (). A minority of CIDP patients, some with specific phenotypes and lack of response to usual therapies, have been identified as demonstrating antibodies to a number of nodal proteins. As an illustrative example, anti-neurofascin-155 IgG4 antibody-positive cases, with a characteristic phenotype of early-onset ataxia, tremor and central nervous system involvement, are few in number (<10%), unresponsive to steroids or immunoglobulins (), although may show some response to the anti-CD20 monoclonal antibody, rituximab ().
    Migraine is a neuro-vascular disease characterized by recurrent attacks of moderate to severe headache, lasting 4–72h and associated with nausea/vomiting and sensitivity to light and noise. Its remarkable prevalence together with the high likelihood of overtreatment carries significant clinical and economic implications. Although plenty of studies have investigated the possible association of migraine and cardiovascular diseases, especially stroke, the nature of this complex, bidirectional link is still obscure ().