Abstract
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker.
Highlights
Inflammatory polyneuropathies constitute disabling autoimmune mediated disorders of the peripheral nervous system (PNS)
We had previously established intercellular adhesion molecule (ICAM)-1-/-non-obese diabetic (NOD) mice as a novel animal model of human Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) [16]. We asked whether this model could help to improve our understanding of CIDP treatments and we tested whether Intravenous immunoglobulins (IVIg) are effective in ICAM-1-/-NOD mice
Cumulative neuritis incidence in the placebo group increased to 91% in contrast to 69% in the IVIg 3x group indicating a reduction by IVIg 3x treatment the survival analysis did not reach significance (Fig 1C)
Summary
Inflammatory polyneuropathies constitute disabling autoimmune mediated disorders of the peripheral nervous system (PNS). Acute and chronic variants have been described. The acute Guillain-Barré syndrome (GBS) features rapid onset monophasic inflammation of the PNS [1, 2] and experimental autoimmune neuritis (EAN) serves as an animal model of its demyelinating variant [3]. Response to IVIg in Chronic Neuritis in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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