Analysis of immune cells and vaccine antibody response in humans after thymectomy

Abstract

Introduction and aim: The immunological effects of thymectomy in adults are largely unknown. Several studies following thymectomised children have concluded that immunological ageing may be precipitated by thymectomy, which has serious long-term implications. We set out to investigate the immunological impact of thymectomy in adults and to determine if immunological ageing is expedited, or vaccine poor responses are influenced by, thymectomy in adults. Methods: We performed a retrospective case-controlled study on 22 subjects including eight thymectomised individuals who had their operation between 1990 and 2012, as well as a pilot case-controlled prospective cohort study of 12 subjects including three thymectomised individuals. Consecutive consenting subjects who underwent thymectomy, parathyroid, thyroid or thoracic surgery at The Canberra Hospital, Australia during 2013-2014 were followed prospectively over 12 months with serial blood tests and a single dose of Hepatitis A and B vaccine at 1-month post operation. Comprehensive T cell subset analysis was performed. Results: We have demonstrated that the removal of the adult thymus results in some alterations in immune profile. The most consistent findings amongst the two studies include a reduced proportion of CD4+CD31- cells undergoing recent proliferation (p<0.05) with a concomitant higher proportion of dividing cells displaying a naive phenotype within the thymectomised group (p<0.05). In contrast to children undergoing thymectomy, we found that proportions of recent thymic emigrant cells remained stable post thymectomy. In relation to immunological ageing post thymectomy, we found increases in the proportion of CD8+ cells (p<0.05) as well as trends towards increased proportions of senescent cells such as CD8+CCR7-CD45RA+CD57+ in the cohort study, yet contrasting results were found in the retrospective study. Significant responses to the Hepatitis A vaccine was seen in three of the eight controls, whereas none of the thymectomised group demonstrated an appreciable response. Discussion: To our knowledge, our study is the world's first case-controlled prospective cohort study investigating the effects of thymectomy in adults. It raises some questions as to the long-held belief that the adult thymus is essentially non-functional and its removal is achieved without immune sequelae. We have demonstrated several changes in T cell subsets as well as some suggestion of reduced responses to vaccines in the thymectomised group compared with controls who underwent a similar operation without thymectomy. Conclusion: The full immunological impact of adult thymectomy remains to be fully elucidated. Our study provides some minor evidence that thymectomy may contribute to alterations in replicating T cell subsets, and possibly reduce vaccine responsiveness. Larger studies are recommended to validate these findings.