The impact of penetrating abdominal trauma on gut-associated lymphoid tissue and the influence of HIV-infection
Date
2021
Authors
Mauser, Martin Ernst
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Abstract
Background:
The gut associated lymphoid tissue (GALT) of the bowel with different lymphocyte
subpopulations as an important pillar of the human immune system has never been
investigated in the context of trauma; neither the short-term histological trauma induced changes in the GALT, nor its impact on the outcome after trauma surgery.
Furthermore, it has never been investigated whether the preexisting altered GALT
of HIV-seropositive trauma patients compromises their postoperative course.
Methods:
This prospective, longitudinal proof-of-concept study included patients who required
damage control surgery after abdominal gunshot wounds with small bowel
involvement. Bowel specimens were obtained during the index and relook
operations, and the T-lymphocytic quantity therein analysed via
immunohistochemistry. We investigated how the lymphocyte structure and numbers
of the GALT altered, and whether the extent and nature of these changes had an
impact on the postoperative outcome with regard to septic and surgical
complications.
Results:
In total, 62 patients were included in the study of which 38 patients were HIV seronegative and 24 were HIV-seropositive. HIV-seropositive patients had a
significantly lower quantity of CD4+ T cells in the GALT compared to the HIV seronegative patients (p = 0,0001), which was also associated with a significantly
higher rate of septic complications in the postoperative course. The main
histological changes between the index and relook specimen was a shift of CD8+ T
cells from the lamina propria (LP) into the epithelium and a decrease of T-
VI
lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells
was associated with a more extensive enterocyte apoptosis, and correlated
significantly, positively with the number of postoperative septic complications.
Conclusions:
The compromised GALT in HIV-seropositive patients may predispose these patients
to postoperative septic complications. Antiretroviral therapy does not result in an
adequate immune reconstitution in this tissue. Hence, safe surgery and vigilant
postoperative care with early, aggressive diagnostic investigations and a low
threshold for relook operations if the postoperative course does not progress as
expected, is of paramount importance for these patients.
Trauma induces an immune cell-driven impairment of the intestinal epithelium, as
well as an increased apoptosis of lymphocytes in the LP which is associated with a
worse clinical outcome. The underlying mechanism suggests that a therapeutic
approach to minimize apoptosis in the intestine may impact the outcome of severely
injured trauma patients
Description
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, 2021