Relationship between endotoxin core, staphylococcal and varicella antibody levels and outcome following aortic valve replacement surgery: a prospective observational study

Andrew Smith, Sarka Moravcova, Thomas A Treibel, Patricia Colque-Navarro, Roland Mollby, James C Moon, Colin Hamilton-Davies, Andrew Smith, Sarka Moravcova, Thomas A Treibel, Patricia Colque-Navarro, Roland Mollby, James C Moon, Colin Hamilton-Davies

Abstract

Background: Morbidity and mortality following cardiac valve surgery is high. Immunity is an important contributor to outcome. This study examines the relationship of staphylococcal and endotoxin antibody levels to outcome following cardiac surgery.

Methods: Using enzyme-linked immunosorbent assays (ELISA), we measured pre-operative levels of antibodies to endotoxin core (EndoCAb); 3 common staphylococcal epitopes and varicella on saved serum of 60 adult patients scheduled to undergo elective primary surgical aortic valve replacement (AVR). Primary outcome measure was post-operative length of stay (LOS) in hospital with secondary outcomes being development of infective complications, length of stay on the intensive care unit (ICU) and 30-day mortality. Patients were quartiled according to antibody levels and outcomes compared between the quartile groups using Mann-Whitney tests for length of stay and Fisher's test for development of infection.

Results: Sixty patients (34 M, 26 F) were recruited with mean age 73 years (IQR 66-78), mean body mass index (BMI) 27.7 (IQR 25-31) and EuroSCORE II 1.44 (0.95-1.99). Those patients in the lower quartile for pre-operative antibody level had a longer post-operative stay than the upper quartile. EndoCAb (median IgG level Q1 42.2 MU/ml vs Q4 256 MU/ml) 9 vs 6 days, p = 0.025; alpha-toxin (median IgG level Q1 63 U vs Q4 558 U) 10 vs 7 days, p = 0.034; teichoic acid (median IgG level Q1 14 U vs Q4 419 U) 10 vs 8 days, p = 0.441; staphylococcal enterotoxin A (median IgG level Q1 55 U vs Q4 427 U) 9 vs 7 days, p = 0.865; varicella zoster (median IgG level Q1 1.325 U vs Q4 2.54 U) 8 vs 7 days, p = 1.0; and combined antibody levels 10 vs 6 days, p = 0.017. There were no differences in the number developing post-operative infections for each antibody type. The combined antibody analysis suggested a reduction in proportion of individuals developing infection from the upper vs lower quartile: 0 vs 0.33, p = 0.042.

Conclusions: This study again suggests the inverse relationship between endotoxin core antibody levels and outcome following aortic valve surgery as well as suggesting a similar relationship with antibodies to staphylococcus. There is no such relationship for antibody levels against an organism not providing a peri-operative threat. Understanding this relationship may enable therapeutic manipulation of immune status, re-evaluation of risk and further investigation of the low immune state.

Trial registration: The patients in this study are a sub-group of the RELIEF AS study.ClinicalTrials.gov identifier NCT02174471.

Keywords: Cardiac surgical procedures; Core endotoxin; Immunity; Sepsis; Staphylococcus.

Conflict of interest statement

All patients provided written consent to participate.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Patient cohort divided into quartiles for each measured antibody level. The median antibody level for each quartile is given. Median length of post-operative stay for each quartile (bars) and trend-line (blue line) and the median EuroSCORE II (number, yellow dot) is displayed for each group. (Q1––quartile 1, etc.)
Fig. 2
Fig. 2
Patient cohort divided into quartiles for measured antibody level to varicella-zoster virus (VZV). The median antibody level for each quartile is given. Median length of post-operative stay for each quartile (bars) and trend-line (blue line) and the median EuroSCORE II (number, yellow dot) is displayed for each group. (Q1––quartile 1, etc.)
Fig. 3
Fig. 3
Patient cohort divided into quartiles for combined, ranked antibody levels for the four antibodies. Median length of post-operative stay for each quartile (bars) and trend-line (blue line) and the median EuroSCORE II (number, yellow dot) is displayed for each group. (Q1––quartile 1, etc.)

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