Antineutrophil cytoplasmic antibody-associated renal vasculitis treated with autologous mesenchymal stromal cells: evaluation of the contribution of immune-mediated mechanisms.
We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10(6) cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.
Unità Complessa di Nefrologia Dialisi e Trapianto, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo e Università di Pavia, Pavia, Italy.
Marilena
M
Gregorini
Rita
R
Maccario
Maria Antonietta
MA
Avanzini
Valeria
V
Corradetti
Antonia
A
Moretta
Carmelo
C
Libetta
Pasquale
P
Esposito
Francesca
F
Bosio
Antonio
A
Dal Canton
Teresa
T
Rampino
D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000601:surgery*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
AAV; ANCA; ANCA with a perinuclear staining pattern; ANCA-associated vasculitis; BVAS; Birmingham Vasculitis Activity Score; CTL; CYC; IL; MSC; NK; PBMC; PHA; RTX; TNF; Treg; antineutrophil cytoplasmic antibody; cyclophosphamide; cytotoxic T lymphocyte; interleukin; mesenchymal stromal cell; natural killer; pANCA; peripheral blood mononuclear cell; phytohemagglutin; regulatory T cell; rituximab; tumor necrosis factor