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Mechanistic effects of IVIg in neuroinflammatory diseases: conclusions based on clinicopathologic correlations.

[inclusion body myositis]

The mechanisms of action of IVIg on immunoregulatory and neuroinflammatory network have been predominantly based on in vitro experiments and animal studies, rather than direct effects on human tissues. Based on clinicopathologic correlations and tissues obtained before and after IVIg therapy, the better documented and clinically-relevant in-vivo actions of IVIg include effects on: a) Antibodies. An extracted antigen-specific anti-immunoglobulin (idiotypic) fraction appears partially responsible for its effect in myasthenia gravis and GBS; b) Complement. Sera from Dermatomyositis (DM) patients responding to IVIg, inhibit complement consumption and intercept MAC formation leading to disappearance of MAC deposits in the repeated muscle biopsies and normalization of muscle tissue; c) Genes. In repeated muscle biopsies from DM patients who improved after IVIg, but not from Inclusion-Body-Myositis (IBM) who did not improve, there is a 2-fold alteration of 2206 tissue genes associated with inflammation, fibrosis, tissue remodeling and regeneration; and d) degenerative-proinflammatory molecules and β-amyloid, implicated in neurodegenerative CNS diseases and IBM. In repeated muscle biopsies of IBM patients who did not respond to IVIg, the mRNA or protein expression for chemokines, IFN-γ, TGF-ß, IL-10, Ubiquitin and aB-crystallin is reduced, but not for the key molecules ICOS, ICOSL, IL-6, IL1-β, perforin, APP, nitric oxide synthase and nitrotyrosine, in spite of good IVIg penetration in muscles. Collectively, the selective effectiveness of IVIg in human diseases seems to correlate in vivo with inhibition of causative inflammatory mediators. Study of accessible tissues before and after therapy and clinicopathologic correlations, may help explain the differential effect of IVIg in autoimmune or neuroinflammatory diseases.

Diseases presenting "repeated muscle biopsies and normalization of muscle tissue" symptom

  • inclusion body myositis

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