Transplantation outcomes are believed to be influenced by a generalized inflammatory state caused by brain death itself or events in the peri-transplant period. Studies on the immunological effects of brain death in humans typically examine serum markers of inflammation and biopsies of a single organ. These studies less frequently contain cellular data and none examine multiple cell lineages and tissue sites, where most immune cells[mdash]innate and adaptive[mdash]reside.

Through a collaboration and research protocol with LiveOnNY, the organ procurement organization for metropolitan New York, our lab obtained blood, bone marrow, lymphoid (spleen, iliac/lung/mesenteric lymph nodes), and mucosal (lung and intestine) tissue (10 sites) from diverse, research-consented organ donors (aged 0-77; n=216) at the time of organ procurement. Inflammatory cytokines in donor blood were analyzed using bead arrays, and tissue myeloid/lymphoid immune cell composition was determined using flow cytometry. This data was then correlated to various clinical parameters (e.g., cause of death, length of brain death, use of steroids, presence of infection, etc.).

In our donors, the overall distribution of myeloid and lymphoid cells in multiple blood, lymphoid, and mucosal sites was not greatly affected by clinical variation surrounding brain death. Monocytes and neutrophils were the prevalent immune cells in circulation and blood-rich sites, where their frequency varied most. In contrast, T and B cell ratios varied more in the lung, lymph nodes, and intestines. However, this variation in immune cells did not correlate with variations in clinical parameters. Cause of death, especially anoxia, was the clinical factor with the greatest impact on both myeloid and lymphoid lineages. Certain inflammatory cytokines, especially IL-6 (p=0.0013), were upregulated in the serum of most brain dead donors.

Myeloid and lymphoid cell populations are stably maintained in tissues despite the wide clinical variation seen, suggesting no overt inflammatory response within tissues secondary to brain death. Serum IL-6, IL-8, and IL-10 levels are upregulated in many donors, particularly those with infections and lung injuries.

CITATION INFORMATION: Carpenter D, Matsuoka N, Thome J, Granot T, Gordon C, Kumar B, Senda T, Miron M, Weiner J, Griesemer A, Farber D. The Immunologic Profile of Brain Death in Humans: A Whole-Body Analysis. Am J Transplant. 2016;16 (suppl 3).

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