Antineutrophil Cytoplasmic Antibody-Associated Renal Vasculitis Treated With Autologous Mesenchymal Stromal Cells: Evaluation of the Contribution of Immune- Mediated Mechanisms  Marilena Gregorini, MD, PhD, Rita Maccario, PhD, Maria Antonietta Avanzini, PhD, Valeria Corradetti, MD, Antonia Moretta, PhD, Carmelo Libetta, MD, PhD, Pasquale Esposito, MD, PhD, Francesca Bosio, MD, Antonio Dal Canton, MD, PhD, Teresa Rampino, MD  Mayo Clinic Proceedings  Volume 88, Issue 10, Pages 1174-1179 (October 2013) DOI: 10.1016/j.mayocp.2013.06.021 Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Representative sections of renal biopsies performed before the first (A) and second (B) mesenchymal stromal cell infusions (periodic acid–Schiff, original magnification ×200). Mayo Clinic Proceedings 2013 88, 1174-1179DOI: (10.1016/j.mayocp.2013.06.021) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 A, Phytohemagglutin (PHA)-induced in vitro proliferation of patient's peripheral blood mononuclear cells (PBMCs) before and at different time points after mesenchymal stromal cell (MSC) infusions (PBMCs alone). In vitro inhibition of PHA-induced PBMC proliferation by MSCs is reported in the same panel; MSCs were added to in vitro cultures at different MSC:PBMC ratios. ∗Results are expressed as stimulation index = count per minute stimulated/count per minute unstimulated. Orange bar = before first MSC infusion (I MSC); blue bar = 1 month after I MSC infusion; brown bar = before second MSC infusion (II MSC); yellow bar = 1 month after II MSC infusion. B, CD3-redirected cytotoxic T-lymphocyte activity of patient's PBMCs alone (orange bar) or co-cultured for 24 hours with MSCs (blue bar), measured at different time points. ∗Results are expressed as percentage of specific lysis of target cells at an effector to target ratio of 10:1. C, Immunoglobulin serum levels at different time points. To convert IgA and IgM to mg/L, multiply by 10; to convert IgG to g/L, multiply by 0.01. rr = reference range; RTX = rituximab. D, Percentage of activated T lymphocytes (CD4+CD25+, orange line) and regulatory T cells (CD4+CD25+Foxp3+, blue line) at different time points. ∗CD4+CD25+ cells are expressed as a percentage of gated CD4+ T lymphocytes. †CD4+CD25+Foxp3+ cells are expressed as a percentage of gated CD4+CD25+ cells. E, Serum interferon-γ (orange line), interleukin 6 (blue line), and tumor necrosis factor (brown line) levels at different time points. Mayo Clinic Proceedings 2013 88, 1174-1179DOI: (10.1016/j.mayocp.2013.06.021) Copyright © 2013 Mayo Foundation for Medical Education and Research Terms and Conditions