Complement Terminal Pathway Activation is Associated with Organ Failure in Sepsis Patients

Abstract

Background: Complement plays a pivotal role in the immune response to infection. Several studies demonstrated complement activation in sepsis, yet little is known of the relationship of complement terminal pathway activation and the clinical characteristics of sepsis patients. Therefore, we investigated serum C5, soluble C5b-9 (sC5b-9), and soluble CD59 (sCD59) and their relation to organ failure in sepsis patients in the intensive care unit (ICU). Methods: In this prospective cohort study, all available patients admitted to the adult ICUs between June 2020 and January 2021 were included. Patients were divided into sepsis and nonsepsis groups according to the Sepsis-3 criteria, serum samples from both groups were investigated for the levels of C5, sC5b-9, and sCD59 using commercial sandwich ELISA kits. Results: We analyzed 79 serum samples, 36 were from sepsis patients. We found that sepsis patients had significantly lower C5 (83.6± 28.4 vs 104.4± 32.0 µg/mL, p = 0.004) and higher sCD59 (380.7± 170.5 vs 288.9± 92.5 ng/mL, p = 0.016). sC5b-9, although higher in sepsis patients, did not reach statistical significance (1.5± 0.8 µg/mL vs 1.3± 0.7 µg/mL, p = 0.293). Sepsis patients who died during their ICU stay had significantly higher sCD59 compared to those who survived (437.0 ± 176.7 vs 267.8 ± 79.7 ng/mL, p = 0.003, respectively). Additionally, C5 and sCD59 both correlated to SOFA score in the sepsis group (r s = −0.44, P = 0.007 and = 0.43, P = 0.009, respectively), and a similar correlation was not found in the non-sepsis group. Discussion: In sepsis patients, levels of C5 and sCD59, but not sC5b-9, correlated to the severity of organ damage measured by SOFA. A similar correlation was not found in nonsepsis patients. This indicated that organ damage associated with sepsis led to a more pronounced terminal pathway activation than in non-sepsis patients, it also indicated the potential of using C5 and sCD59 to reflect sepsis severity.

Predictive value of soluble CD59 for poor 28-day neurological prognosis and all-cause mortality in patients after cardiopulmonary resuscitation: a prospective observatory study

“…Serum sCD59, inhibiting the formation of C5b-9 through preventing the incorporation and polymerization of C9 on cell membranes, was elevated in patients with sepsis, severe acute pancreatitis, acute myocardial infarction, and lung transplantation [ 19 , 27 , 30 , 31 ]. The exact mechanisms how CD59 sheds from the cell membrane and is released into the circulation in a soluble form (sCD59) are complex.…”

“…Therefore, the elevated serum complement activation products, including C3a, C5a, and sC5b-9, have been reported to be associated with post-cardiac arrest immunoinflammatory response and poor prognosis [7,11,29], which is consistent with our result that the non-survivors had higher concentrations of serum C3a, C5a and sC5b-9 than the survivors. Serum sCD59, inhibiting the formation of C5b-9 through preventing the incorporation and polymerization of C9 on cell membranes, was elevated in patients with sepsis, severe acute pancreatitis, acute myocardial infarction, and lung transplantation [19,27,30,31]. The exact mechanisms how CD59 sheds from the cell membrane and is released into the circulation in a soluble form (sCD59) are complex.…”

“…Circulating sC5b-9 has been observed to be elevated in many clinical settings, including sepsis, burn injury, transplantation, and trauma, which leads to the secretion of pro-inflammatory mediators and thus correlates with prognosis and neurological disability [12][13][14][15][16][17]. Thus, the complement inhibitor CD59 that blocks the assembly of C5b-9 through prohibiting the coupling of C9 to C5b-8, may be involved in inflammatory response and neurological dysfunction [18,19].…”

Generalized peakgroup scoring boosts identification rates and accuracy in mass spectrometry based discovery proteomics

“…The high accuracy and separating power of this panel of 20 proteins indicates that they would provide a good starting point for investigation as potential clinical markers. In fact, many of these proteins have already been identified and studied as potential clinical sepsis markers or markers for infection and inflammation [21, 44, 60, 16, 45, 36, 37, 67, 64, 10, 62, 23, 9, 55, 1, 25]. The majority of the top 20 proteins were up-regulated in the more severe subphenotype 2.…”

Markers of Bronchiolitis Obliterans Syndrome after Lung Transplant: Between Old Knowledge and Future Perspective

“…CD59 has been investigated in different diseases as a predictive biomarker of outcome and disease progression [ 105 ]. In sepsis, serum concentrations of soluble CD59 (sCD59) were correlated with the severity of organ damage [ 106 ]. Budding et al were the first to investigate the role of CD59 in lung transplant, showing that in chronic lung allograft dysfunction, BOS patients had higher serum concentrations of sCD59 than non-BOS patients [ 56 ].…”