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Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Short report

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy

Authors: Mohan S. Maddur, Emmanuel Stephen-Victor, Mrinmoy Das, Praveen Prakhar, Varun K. Sharma, Vikas Singh, Magalie Rabin, Jamma Trinath, Kithiganahalli N. Balaji, Francis Bolgert, Jean-Michel Vallat, Laurent Magy, Srini V. Kaveri, Jagadeesh Bayry

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking.

Methods

Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4–5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA.

Results

The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with Treg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and Treg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. Treg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α.

Conclusion

Treg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. Treg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.
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Metadata
Title
Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy
Authors
Mohan S. Maddur
Emmanuel Stephen-Victor
Mrinmoy Das
Praveen Prakhar
Varun K. Sharma
Vikas Singh
Magalie Rabin
Jamma Trinath
Kithiganahalli N. Balaji
Francis Bolgert
Jean-Michel Vallat
Laurent Magy
Srini V. Kaveri
Jagadeesh Bayry
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0818-5

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