BACKGROUND: B-cell depletion is a common treatment of antibody-mediated rejection (ABMR). We sought to determine the specific immunopathologic effects of this therapeutic approach in kidney transplantation. METHODS: This was a prospective observational study of kidney transplant recipients diagnosed with late ABMR (>3 months after transplant). Patients received treatment with pulse steroids, IVIG, and rituximab. Donor specific HLA antibodies (DSA), kidney allograft pathology, renal function, immune cell phenotypes, and 47 circulating cytokines were assessed at baseline and at three months. RESULTS: We enrolled 23 patients in this study between April 2015 and March 2019. The majority of patients were male (74%) and Caucasian (78%) with an average age of 45.6±13.8 years. ABMR was diagnosed at 6.8±5.9 years (4 months-25 years) post-transplant. Treatment was associated with a significant decline in circulating HLA class I DSA (P=0.003) and class II DSA (P=0.002) and peritubular capillaritis (ptc, P=0.04) compared to baseline. Serum creatinine, BUN, eGFR, and proteinuria (UPC) remained stable. Circulating B-cells were depleted to barely detectable levels (P≤0.001), whereas BAFF (P=0.001), APRIL (P<0.001), and IL-10 (P=0.02), levels increased significantly post-treatment. Notably, there was a significant rise in circulating CD4+ (P=0.02) and CD8+ T-cells (P=0.003). We also noted a significant correlation between circulating cytotoxic CD8+ T-cells and BAFF (P=0.05), regulatory T-cells and IL10 (P=0.002), and HLA class I DSA (P=0.005). CONCLUSIONS: Short-term pulse steroids/IVIG/rituximab therapy was associated with inhibition of ABMR (DSA and ptc), stabilization of kidney function, and increased regulatory B-cell and T-cell survival cytokines. Additional studies are needed to understand the implications of B cell-depletion on the crosstalk between T-cells, B-cells, and humoral components that regulate ABMR.
BACKGROUND: B-cell depletion is a common treatment of antibody-mediated rejection (ABMR). We sought to determine the specific immunopathologic effects of this therapeutic approach in kidney transplantation. METHODS: This was a prospective observational study of kidney transplant recipients diagnosed with late ABMR (>3 months after transplant). Patients received treatment with pulse steroids, IVIG, and rituximab. Donor specific HLA antibodies (DSA), kidney allograft pathology, renal function, immune cell phenotypes, and 47 circulating cytokines were assessed at baseline and at three months. RESULTS: We enrolled 23 patients in this study between April 2015 and March 2019. The majority of patients were male (74%) and Caucasian (78%) with an average age of 45.6±13.8 years. ABMR was diagnosed at 6.8±5.9 years (4 months-25 years) post-transplant. Treatment was associated with a significant decline in circulating HLA class I DSA (P=0.003) and class II DSA (P=0.002) and peritubular capillaritis (ptc, P=0.04) compared to baseline. Serum creatinine, BUN, eGFR, and proteinuria (UPC) remained stable. Circulating B-cells were depleted to barely detectable levels (P≤0.001), whereas BAFF (P=0.001), APRIL (P<0.001), and IL-10 (P=0.02), levels increased significantly post-treatment. Notably, there was a significant rise in circulating CD4+ (P=0.02) and CD8+ T-cells (P=0.003). We also noted a significant correlation between circulating cytotoxic CD8+ T-cells and BAFF (P=0.05), regulatory T-cells and IL10 (P=0.002), and HLA class I DSA (P=0.005). CONCLUSIONS: Short-term pulse steroids/IVIG/rituximab therapy was associated with inhibition of ABMR (DSA and ptc), stabilization of kidney function, and increased regulatory B-cell and T-cell survival cytokines. Additional studies are needed to understand the implications of B cell-depletion on the crosstalk between T-cells, B-cells, and humoral components that regulate ABMR.
Authors: Rodney P E Pollard; Wayel H Abdulahad; Arjan Vissink; Nishath Hamza; Johannes G M Burgerhof; Jiska M Meijer; Annie Visser; Minke G Huitema; Fred K L Spijkervet; Cees G M Kallenberg; Hendrika Bootsma; Frans G M Kroese Journal: Ann Rheum Dis Date: 2012-07-31 Impact factor: 19.103
Authors: Stephan Immenschuh; Eva Zilian; Max E Dämmrich; Anke Schwarz; Wilfried Gwinner; Jan Ulrich Becker; Cornelia A Blume Journal: Transplantation Date: 2015-01 Impact factor: 4.939
Authors: Jens V Stein; Marta López-Fraga; Fernando A Elustondo; Carla E Carvalho-Pinto; Dolores Rodríguez; Ruth Gómez-Caro; Joan De Jong; Carlos Martínez-A; Jan Paul Medema; Michael Hahne Journal: J Clin Invest Date: 2002-06 Impact factor: 14.808
Authors: C Lefaucheur; D Nochy; J Andrade; J Verine; C Gautreau; D Charron; G S Hill; D Glotz; C Suberbielle-Boissel Journal: Am J Transplant Date: 2009-05 Impact factor: 8.086
Authors: M Haas; A Loupy; C Lefaucheur; C Roufosse; D Glotz; D Seron; B J Nankivell; P F Halloran; R B Colvin; Enver Akalin; N Alachkar; S Bagnasco; Y Bouatou; J U Becker; L D Cornell; J P Duong van Huyen; I W Gibson; Edward S Kraus; R B Mannon; M Naesens; V Nickeleit; P Nickerson; D L Segev; H K Singh; M Stegall; P Randhawa; L Racusen; K Solez; M Mengel Journal: Am J Transplant Date: 2018-01-21 Impact factor: 8.086