BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.
BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.
Authors: Hong Xu; Paula M Chilton; Michael K Tanner; Yiming Huang; Carrie L Schanie; Mariano Dy-Liacco; Jun Yan; Suzanne T Ildstad Journal: Blood Date: 2006-08-03 Impact factor: 22.113
Authors: Munekazu Yamakuchi; Nancy C Kirkiles-Smith; Marcella Ferlito; Scott J Cameron; Clare Bao; Karen Fox-Talbot; Barbara A Wasowska; William M Baldwin; Jordan S Pober; Charles J Lowenstein Journal: Proc Natl Acad Sci U S A Date: 2007-01-17 Impact factor: 11.205
Authors: Jean Kwun; Marie Matignon; Miriam Manook; Soulef Guendouz; Vincent Audard; David Kheav; Elsa Poullot; Chantal Gautreau; Brian Ezekian; Diane Bodez; Thibault Damy; Laureline Faivre; Dehbia Menouch; Janghoon Yoon; Jaeberm Park; Karim Belhadj; Dongfeng Chen; Alyssa M Bilewski; John S Yi; Bradley Collins; Mark Stegall; Alton B Farris; Stuart Knechtle; Philippe Grimbert Journal: J Am Soc Nephrol Date: 2019-06-21 Impact factor: 10.121
Authors: Jeremy Ryan A Peña; Susan L Saidman; Timothy C Girouard; Erin Meister; Walter H Dzik; Robert S Makar Journal: Am J Hematol Date: 2014-06-19 Impact factor: 10.047