The role of changes in adaptive immunity as a factor of unfavorable outcome in abdominal sepsis

Altered immune response in abdominal sepsis (AS) leads to dysregulation of innate and adaptive immunity, followed by immunosuppression. Mortality rates in AS are quite high, thus requiring continued indepth study of the role of adaptive immunity in this condition. The aim of our study was to evaluate the role of changes in adaptive immunity as a factor of an unfavorable AS outcomes. The control groups consisted of 63 conditionally healthy individuals (33 women and 30 men, group 1). 64 patients with AS aged 32-82 years were also observed. According to their clinical outcomes, we discerned group 2 (n = 46) with a favorable outcome and group 3 (n = 18) with a fatal outcome. The studies were conducted on days 1, 3, and 7. The total number of leukocytes and lymphocytes was determined by the Sysmex XT-1800i/XT-2000i hematology analyzer (Japan). The subpopulation composition of lymphocytes was studied in peripheral blood by flow cytofluorometry using Navios 2/6 flow cytometer (Beckman Coulter, USA) with monoclonal antibody conjugates (Beckman Coulter, USA). The concentrations of IgA, IgM, and IgG were determined by solid-phase enzyme immunoassay (JSC "Vector-Best", Russia). The contents of circulating immune complexes were determined with a microplate reader (Labsystems Multiskan Plus, Finland) using the CIK-HEMA test systems (Hema-Medica, Russia). Statistical processing of the results was performed using the statistical package SPSS 17.0. Analysis of adaptive immunity cells in patients with AS revealed lymphocytopenia: deficiency of CD45⁺CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, immunoregulatory index, CD3^-CD19⁺, marker of early activation of T lymphocytes (CD3⁺CD25⁺). A significant relationship was found between the severity of leukocytosis, lymphocytopenia and the outcome of the disease. In cases of favorable outcome, lymphocytopenia was less pronounced than among patients with unfavorable one, along with significantly higher values of the lymphocyte subpopulations: CD45⁺CD3⁺, CD3⁺CD4⁺, immunoregulatory index, CD3^-CD19⁺, CD3⁺CD25⁺, CD3⁺56⁺. Meanwhile, the number of CD3⁺CD8⁺, CD3⁺HLA-DR⁺ lymphocytes in the surviving patients was decreased over 7 days, as compared with the unfavorable outcome group. More pronounced leukocytosis was associated with unfavorable outcome of AS, thus emphasizing severity of the systemic inflammatory response, which is closely associated with severity of clinical course and prognosis of AS. There was a more pronounced lymphocytopenia, a progressive decrease in the following lymphocyte subpopulations compared to the survivors: CD45⁺CD3⁺, CD3⁺CD4⁺, immunoregulatory index, CD3^-CD19⁺, CD3⁺CD25⁺, CD3⁺56⁺. The values of CD3⁺CD8⁺, CD3⁺HLA-DR⁺ lymphocytes in fatal cases were higher than in favorable cases. The results of our study emphasize the need to take into account the state of adaptive immunity in order to more accurately stratify the risk of death and personalize therapeutic strategies.

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