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

Article scientifique 2017 Anglais

Résumé

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 (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. 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. 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 T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

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Maddur, M., Stephen‐Victor, E., Das, M., Prakhar, P., Sharma, V., Singh, V., Rabin, M., Trinath, J., Balaji, K., Bolgert, F., Vallat, J., Magy, L., Kaveri, S., Bayry, J. (2017). Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy. https://doi.org/10.1186/s12974-017-0818-5

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Auteur(s)

Mohan S. Maddur Emmanuel Stephen‐Victor Mrinmoy Das Praveen Prakhar Varun Kumar Sharma Vikas Singh Magalie Rabin Jamma Trinath Kithiganahalli Narayanaswamy Balaji Françis Bolgert Jean‐Michel Vallat Laurent Magy Srini V. Kaveri Jagadeesh Bayry

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