Removal of Donor Human Leukocyte Antigen Class I Proteins With Papain. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Mera, Toshiyuki; Faustman, Denise L.
• Is Part Of: Transplantation. Volume 99:Issue 4(2015)
• Publication Date: 2015-04
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000436
• Languages: English
• ISSNs: 0041-1337

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>Papain is a protease with potential use in transplantation because of its targeted capacity to selectively remove human leukocyte antigen (HLA) class I proteins from donor human cells. However, its proteolytic activity has not been studied under conditions suitable for use in perfusing donor organs, namely, under a temperature of 4°C and dissolution in Belzer-UW solution.</p> </sec> <sec> <title>Methods</title> <p>We test papain's HLA class I removing activity under recognized whole organ transplant conditions of lowered temperature. The activity of papain's substrate selectivity was tested using both a test substrate (casein) and fresh peripheral blood lymphocytes (PBLs). The activity of papain was also tested at 4°C, the temperature of whole organ storage.</p> </sec> <sec> <title>Results</title> <p>We found that papain at a range of concentrations is nearly as active in cleaving the test substrate in Belzer-UW solution as in distilled water. In distilled water, papain is as active in cleaving a test substrate at a temperature of 4°C as compared to its optimal temperature of 37°C, if the incubation time is extended from 10 min to 3 hr. This finding also holds true if papain is dissolved in Belzer-UW solution. In peripheral blood lymphocytes, papain cleaved off HLA class I proteins as effectively at 4°C as at 37°C, provided the incubation time was also extended to 3 hr.</p> </sec> <sec> <title>Conclusion</title> <p>These findings suggest that papain's targeted enzymatic cleavage of donor HLA class I has potential use in the whole organ transplant setting with retained activity at lower temperatures and when activated and dissolved in Belzer-UW solution.</p> </sec> </abstract>