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Shedding of membrane complement inhibitors CD59 and CD46 into the circulation is associated with poor prognosis in acute coronary syndrome patients : a cohort study

Zhong, Baojun LU ; King, Ben LU orcid ; Waziri, Homa LU ; Yndigegn, Troels LU ; Engelbertsen, Daniel LU ; Björkbacka, Harry LU orcid ; Nilsson, Jan LU ; Goncalves, Isabel LU orcid ; Blom, Anna M. LU orcid and Schiopu, Alexandru LU orcid (2024) In Journal of Translational Medicine 22(1).
Abstract

Introduction: The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications. Methods: We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup. Results: Elevated... (More)

Introduction: The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications. Methods: We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup. Results: Elevated sCD46 and sCD59 were correlated with increased levels of inflammatory mediators and metalloproteinases in plasma, and were associated with increased risk for MACE in Cox proportional hazard models adjusted for cardiovascular risk factors and revascularization [HR 95% CI 1.24 (1.02–1.52), p = 0.034 for sCD46 and 1.18 (1.00–1.38), p = 0.049 for sCD59]. Elevated sCD59 was also associated with higher incidence of HF [HR 95% CI 1.41 (1.15–1.74), p = 0.001], and with lower left ventricular ejection fraction at 1-year post-ACS (Spearman r = − 0.234, p = 0.020). We found no associations between plasma levels of the proteins at 6 weeks and outcomes. Conclusions: Shedding of the complement regulators CD46 and CD59 in plasma in the acute phase of ACS is associated with a negative prognosis. Plasma sCD46 and sCD59 could reflect the degree of local immune activation and serve as prognostic biomarkers in ACS patients.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Acute coronary syndrome (ACS), CD46, CD59, Complement, Heart failure (HF), Inflammation, Major adverse cardiovascular events (MACE), Matrix metalloproteinases
in
Journal of Translational Medicine
volume
22
issue
1
article number
1011
publisher
BioMed Central (BMC)
external identifiers
  • pmid:39523332
  • scopus:85209704722
ISSN
1479-5876
DOI
10.1186/s12967-024-05781-9
language
English
LU publication?
yes
id
9a8edb7f-18d2-488f-ab4b-844237fad374
date added to LUP
2025-01-09 09:12:25
date last changed
2025-07-11 00:37:53
@article{9a8edb7f-18d2-488f-ab4b-844237fad374,
  abstract     = {{<p>Introduction: The role of the complement inhibitory proteins CD46 and CD59 in the immune response to an acute coronary syndrome (ACS) is unknown. We investigated the relationships between the shedding of CD46 and CD59 into the circulation, reflected by plasma levels of soluble CD46 and CD59, and the risk for post-ACS complications. Methods: We measured plasma sCD46 and sCD59 in a cohort of 546 ACS patients within 24 h after hospital admission, and after 6-weeks in a subgroup of 114 patients. Study outcomes were incident heart failure (HF), major adverse cardiovascular events (MACE) and mortality during a median follow-up period of up to 3.3 years. Echocardiography at 1-year was performed in the follow-up subgroup. Results: Elevated sCD46 and sCD59 were correlated with increased levels of inflammatory mediators and metalloproteinases in plasma, and were associated with increased risk for MACE in Cox proportional hazard models adjusted for cardiovascular risk factors and revascularization [HR 95% CI 1.24 (1.02–1.52), p = 0.034 for sCD46 and 1.18 (1.00–1.38), p = 0.049 for sCD59]. Elevated sCD59 was also associated with higher incidence of HF [HR 95% CI 1.41 (1.15–1.74), p = 0.001], and with lower left ventricular ejection fraction at 1-year post-ACS (Spearman r = − 0.234, p = 0.020). We found no associations between plasma levels of the proteins at 6 weeks and outcomes. Conclusions: Shedding of the complement regulators CD46 and CD59 in plasma in the acute phase of ACS is associated with a negative prognosis. Plasma sCD46 and sCD59 could reflect the degree of local immune activation and serve as prognostic biomarkers in ACS patients.</p>}},
  author       = {{Zhong, Baojun and King, Ben and Waziri, Homa and Yndigegn, Troels and Engelbertsen, Daniel and Björkbacka, Harry and Nilsson, Jan and Goncalves, Isabel and Blom, Anna M. and Schiopu, Alexandru}},
  issn         = {{1479-5876}},
  keywords     = {{Acute coronary syndrome (ACS); CD46; CD59; Complement; Heart failure (HF); Inflammation; Major adverse cardiovascular events (MACE); Matrix metalloproteinases}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Translational Medicine}},
  title        = {{Shedding of membrane complement inhibitors CD59 and CD46 into the circulation is associated with poor prognosis in acute coronary syndrome patients : a cohort study}},
  url          = {{http://dx.doi.org/10.1186/s12967-024-05781-9}},
  doi          = {{10.1186/s12967-024-05781-9}},
  volume       = {{22}},
  year         = {{2024}},
}