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Liver Transplant: antibody-mediated rejection monitored by C4d
Liver transplantation has become a routine treatment for children with end stage liver failure. Antibody-mediated rejection of the transplant can be monitored by C4d. This recent study utilized the Biomedica “anti-C4d antibody”:
Liver Histopathology in Late Protocol Biopsies after Pediatric Liver Transplantation.
Markiewicz-Kijewska M, Szymańska S, Pyzlak M, Kaliciński P, Teisseyre J, Kowalski A, Jankowska I, Czubkowski P, Ismail H. Children (Basel). 2021 Aug 1;8(8):671. doi: 10.3390/children8080671. PMID: 34438562; PMCID: PMC8392008.
Liver Transplant: antibody-mediated rejection monitored by C4d
√ CE-marked – for IVD use in the EU
√ Widely cited for ICH
√ For kidney, heart, liver and other transplants
Check out the Biomedica anti-C4d antibodies for ICH and FITC.
Abstract
Liver transplantation has become a routine treatment for children with end stage liver failure. Recently, the long term survival of pediatric patients after liver transplantation has improved, with a life expectancy much longer than that of adult recipients, but also with longer exposition of the graft to various injuries, including immunological, inflammatory and others. Biochemical tests, although important, do not always reflect graft injury. The aim of our study was to analyze the histopathology of the graft in late protocol biopsies and correlate it with the clinical and biochemical status of these patients. We analyzed 61 protocol liver biopsies taken from 61 patients. Biopsies were taken 9.03-17.09 years (mean 12.68, median 11.74 years) after transplantation. Liver specimens were examined particularly for the presence and stage of liver fibrosis, inflammation, steatosis, and acute or chronic cellular and humoral rejection. We did not find any abnormalities in 26 (42.6%) liver specimens. None of the patients had signs of cellular or antibody mediated rejection or chronic rejection. In 23 liver biopsies (37.7%), we found non-specific lymphoid infiltrates. Another problem was fibrosis (equal to or more than three on the Ishak scale)-we found it in 17 patients, including seven liver specimens (11.5%) with severe fibrosis (Ishak 5-6). Conclusions: Various pathomorphological abnormalities were found in more than half of patients with a median 11.74 years post-transplant follow-up. Most of them presented normal laboratory liver tests at the same time, suggesting a slow subclinical process leading to pathomorphological abnormalities. No single factor for the development of these abnormalities was found, but our study supports the need for protocol liver biopsies even in patients with normal/almost normal biochemical liver tests.
Liver Transplant: antibody-mediated rejection monitored by C4d
Related publications
Immunostaining Patterns of Posttransplant Liver Biopsies Using 2 Anti-C4d Antibodies
Chen L, Himmelfarb EA, Sun M, Choi EK, Fan L, Lai J, Kim CJ, Xu H, Wang HL. Appl Immunohistochem Mol Morphol. 2020 Feb;28(2):146-153. doi: 10.1097/PAI.0000000000000723. PMID: 32044883.
Citation Biomedica C4d antibody (purchased through Alpco, US, cat. no. BI-RC4D)
Abstract
Histopathologic diagnosis of antibody-mediated rejection in posttransplant liver biopsies is challenging. The recently proposed diagnostic criteria by the Banff Working Group on Liver Allograft Pathology require positive C4d immunohistochemical staining to establish the diagnosis. However, the reported C4d staining patterns vary widely in different studies. One potential explanation may be due to different antibody preparations used by different investigators. In this study, posttransplant liver biopsies from 69 patients histopathologically diagnosed with acute cellular rejection, chronic rejection, or recurrent hepatitis C were immunohistochemically stained using 2 polyclonal anti-C4d antibodies. On the basis of the distribution of C4d immunoreactivity, 5 different staining patterns were observed: portal vein and capillary, hepatic artery, portal stroma, central vein, and sinusoids. The frequency, extent, and intensity of positive C4d staining with the 2 antibody preparations differed significantly for portal veins/capillaries and central veins, but not for hepatic arteries and portal stroma. Positive sinusoidal staining was seen in only 1 case. There were no significant differences in the frequency, extent, and intensity of positive C4d staining among the acute cellular rejection, chronic rejection, and recurrent hepatitis C groups with the 2 anti-C4d antibodies. These data show that different anti-C4d antibodies can show different staining patterns, which may lead to different interpretation. Caution is thus needed when selecting C4d antibodies for clinical use to aid in the diagnosis of antibody-mediated rejection.
Antibody-Mediated Rejection After Liver Transplant
Lee M. Gastroenterol Clin North Am. 2017 Jun;46(2):297-309. doi: 10.1016/j.gtc.2017.01.005. PMID: 28506366.
Abstract
Antibody-mediated rejection (AMR) in liver transplants is a field in its infancy compared with its allograft cohorts of the kidney and lung. Acute AMR is diagnosed based on specific clinical and histopathologic criteria: serum donor specific antibodies, C4d staining, histopathologic findings on liver biopsy, and exclusion of other entities. In contrast, the histologic features of chronic AMR are not as specific and it is a more challenging diagnosis to make. Treatments of acute and chronic AMR include some combination of steroids, immune-modulating agents, intravenous immunoglobulin, plasmapheresis, and proteasome inhibitors.
Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes
Husain AN, Mirza KM, Fedson SE. J Heart Lung Transplant. 2017 Dec;36(12):1329-1335. doi: 10.1016/j.healun.2017.09.004. Epub 2017 Sep 14. PMID: 28988608.
Luk A, Alba AC, Butany J, Tinckam K, Delgado D, Ross HJ. Transpl Int. 2015 Jul;28(7):857-63. doi: 10.1111/tri.12560. Epub 2015 Mar 27. PMID: 25778989.