Guoqiang Zhang1, Hidetaka Hara2, Takayuki Yamamoto2, Qi Li2, Abhijit Jagdale2, Yong Li3, David K C Cooper2, Hayato Iwase4. 1. Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. 2. Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. 3. Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China. Electronic address: yfylyong@163.com. 4. Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: hiwase@uabmc.edu.
Abstract
BACKGROUND: There is well-documented systemic inflammatory response in xenograft recipients to the presence of a pig graft. Serum amyloid A (SAA) is an inflammatory marker that is elevated in various pathological states. The assay used to measure it is (i) simple, (ii) relatively inexpensive, and (iii) provides an answer within minutes. METHOD: The levels of SAA (n = 11) and C-reactive protein (C-RP) (n = 8) were measured retrospectively in the serum of baboons with pig kidney transplants, who received therapy with an IL-6R inhibitor and a TNF-α antagonist. Immunohistochemistry (IHC) was used to identify amyloid A and C-RP expression in the native livers and deposition in the pig kidney grafts. RESULTS: One kidney graft underwent hyperacute rejection, 6 (55%) underwent acute antibody-mediated rejection, 3 baboons (27%) were euthanized for serious systemic infections, and one was euthanized for acute gastric dilatation. The SAA increased temporarily after kidney transplantation, and increased again by the day of euthanasia, indicating moderate (n = 3) or significant (severe) (n = 8) inflammation. In contrast, as the baboons were receiving tocilizumab, C-RP did not increase. There was greater expression of amyloid A in baboon livers (by IHC) than of C-RP (mean OD 53 vs 1, p < 0.01), and greater deposition of amyloid A than C-RP in the pig kidney grafts (mean OD 24 vs 2, p < 0.001). Plasma fibrinogen negatively correlated with the expression of amyloid A in the liver (r = -0.72, p < 0.05). The results of the SAA assay correlated with amyloid A expression in the liver and deposition in the kidney grafts. CONCLUSIONS: SAA is a sensitive, but non-specific, marker for inflammation in baboons with pig kidney grafts, and is not affected by therapy that suppresses the response of C-RP. The SAA assay is a rapid, reliable, and relatively inexpensive method of following the inflammatory state of baboons with pig xenografts.
BACKGROUND: There is well-documented systemic inflammatory response in xenograft recipients to the presence of a pig graft. Serum amyloid A (SAA) is an inflammatory marker that is elevated in various pathological states. The assay used to measure it is (i) simple, (ii) relatively inexpensive, and (iii) provides an answer within minutes. METHOD: The levels of SAA (n = 11) and C-reactive protein (C-RP) (n = 8) were measured retrospectively in the serum of baboons with pig kidney transplants, who received therapy with an IL-6R inhibitor and a TNF-α antagonist. Immunohistochemistry (IHC) was used to identify amyloid A and C-RP expression in the native livers and deposition in the pig kidney grafts. RESULTS: One kidney graft underwent hyperacute rejection, 6 (55%) underwent acute antibody-mediated rejection, 3 baboons (27%) were euthanized for serious systemic infections, and one was euthanized for acute gastric dilatation. The SAA increased temporarily after kidney transplantation, and increased again by the day of euthanasia, indicating moderate (n = 3) or significant (severe) (n = 8) inflammation. In contrast, as the baboons were receiving tocilizumab, C-RP did not increase. There was greater expression of amyloid A in baboon livers (by IHC) than of C-RP (mean OD 53 vs 1, p < 0.01), and greater deposition of amyloid A than C-RP in the pig kidney grafts (mean OD 24 vs 2, p < 0.001). Plasma fibrinogen negatively correlated with the expression of amyloid A in the liver (r = -0.72, p < 0.05). The results of the SAA assay correlated with amyloid A expression in the liver and deposition in the kidney grafts. CONCLUSIONS:SAA is a sensitive, but non-specific, marker for inflammation in baboons with pig kidney grafts, and is not affected by therapy that suppresses the response of C-RP. The SAA assay is a rapid, reliable, and relatively inexpensive method of following the inflammatory state of baboons with pig xenografts.
Authors: Juan Li; Hidetaka Hara; Yi Wang; Charles Esmon; David K C Cooper; Hayato Iwase Journal: J Inflamm (Lond) Date: 2019-05-28 Impact factor: 4.981
Authors: Guoqiang Zhang; Hayato Iwase; Qi Li; Takayuki Yamamoto; Abhijit Jagdale; Mohamed B Ezzelarab; David Ayares; David K C Cooper; Hidetaka Hara; Gangcheng Wang Journal: Front Immunol Date: 2021-12-08 Impact factor: 7.561