PMID- 28320438 OWN - NLM STAT- MEDLINE DCOM- 20171013 LR - 20191210 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 14 IP - 1 DP - 2017 Mar 20 TI - Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy. PG - 58 LID - 10.1186/s12974-017-0818-5 [doi] LID - 58 AB - 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 (T(reg)) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. METHODS: Ten newly diagnosed Guillain-Barre 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-gamma, and tumor necrosis factor alpha (TNF-alpha) 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 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-alpha. CONCLUSION: 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. FAU - Maddur, Mohan S AU - Maddur MS AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. AD - Universite Paris Descartes, UMR S 1138, Paris, 75006, France. AD - Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, 30329, USA. FAU - Stephen-Victor, Emmanuel AU - Stephen-Victor E AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. FAU - Das, Mrinmoy AU - Das M AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. FAU - Prakhar, Praveen AU - Prakhar P AD - Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. FAU - Sharma, Varun K AU - Sharma VK AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. AD - Universite Paris Descartes, UMR S 1138, Paris, 75006, France. FAU - Singh, Vikas AU - Singh V AD - Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. FAU - Rabin, Magalie AU - Rabin M AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. FAU - Trinath, Jamma AU - Trinath J AD - Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. FAU - Balaji, Kithiganahalli N AU - Balaji KN AD - Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India. FAU - Bolgert, Francis AU - Bolgert F AD - Reanimation Neurologique, Neurologie 1, Hopital de la Pitie-Salpetriere, Paris, 75651, France. FAU - Vallat, Jean-Michel AU - Vallat JM AD - Centre de Reference 'Neuropathies Peripheriques Rares' et Service de Neurologie, Hopital Universitaire Limoges, Limoges, 87042, France. FAU - Magy, Laurent AU - Magy L AD - Centre de Reference 'Neuropathies Peripheriques Rares' et Service de Neurologie, Hopital Universitaire Limoges, Limoges, 87042, France. FAU - Kaveri, Srini V AU - Kaveri SV AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. srini.kaveri@crc.jussieu.fr. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. srini.kaveri@crc.jussieu.fr. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. srini.kaveri@crc.jussieu.fr. AD - Universite Paris Descartes, UMR S 1138, Paris, 75006, France. srini.kaveri@crc.jussieu.fr. FAU - Bayry, Jagadeesh AU - Bayry J AD - Institut National de la Sante et de la Recherche Medicale, Unite 1138, Paris, 75006, France. jagadeesh.bayry@crc.jussieu.fr. AD - Centre de Recherche des Cordeliers, Equipe- Immunopathologie et immuno-intervention therapeutique, Paris, 75006, France. jagadeesh.bayry@crc.jussieu.fr. AD - Sorbonne Universites, UPMC Univ Paris 06, UMR S 1138, Paris, 75006, France. jagadeesh.bayry@crc.jussieu.fr. AD - Universite Paris Descartes, UMR S 1138, Paris, 75006, France. jagadeesh.bayry@crc.jussieu.fr. LA - eng PT - Journal Article DEP - 20170320 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Immunologic Factors) RN - 0 (Interleukin-33) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Aged MH - Aged, 80 and over MH - Dinoprostone/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - Follow-Up Studies MH - *Guillain-Barre Syndrome/blood/drug therapy/pathology MH - Humans MH - Immunoglobulins, Intravenous/*therapeutic use MH - Immunologic Factors/*therapeutic use MH - Interleukin-33/*blood MH - Male MH - Middle Aged MH - Outcome Assessment, Health Care MH - Predictive Value of Tests MH - Severity of Illness Index MH - Statistics, Nonparametric MH - T-Lymphocytes, Regulatory/*pathology PMC - PMC5360043 OTO - NOTNLM OT - Clinical response OT - Guillain-Barre syndrome OT - IL-33 OT - IVIG OT - Regulatory T cells OT - TNF-alpha OT - Treg cells EDAT- 2017/03/23 06:00 MHDA- 2017/10/14 06:00 PMCR- 2017/03/20 CRDT- 2017/03/22 06:00 PHST- 2016/10/27 00:00 [received] PHST- 2017/02/18 00:00 [accepted] PHST- 2017/03/22 06:00 [entrez] PHST- 2017/03/23 06:00 [pubmed] PHST- 2017/10/14 06:00 [medline] PHST- 2017/03/20 00:00 [pmc-release] AID - 10.1186/s12974-017-0818-5 [pii] AID - 818 [pii] AID - 10.1186/s12974-017-0818-5 [doi] PST - epublish SO - J Neuroinflammation. 2017 Mar 20;14(1):58. doi: 10.1186/s12974-017-0818-5.