tetano
Editor, Senior Moderator
J Clin Immunol
. 2021 Jul 7.
doi: 10.1007/s10875-021-01061-z. Online ahead of print.
Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality
Maaweya E Hamed[SUP] 1 [/SUP], Asif Naeem[SUP] 2 [/SUP], Haitham Alkadi[SUP] 2 [/SUP], Aref A Alamri[SUP] 3 [/SUP], Ahmad S AlYami[SUP] 4 [/SUP], Abdullah AlJuryyan[SUP] 4 [/SUP], Wael Alturaiki[SUP] 5 [/SUP], Mushira Enani[SUP] 6 [/SUP], Samia T Al-Shouli[SUP] 7 [/SUP], Abdullah M Assiri[SUP] 8 [/SUP], Bandar Alosaimi[SUP] 9 [/SUP]
Affiliations
Abstract
The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.
Keywords: Chemokine; Complement system; Cytokine; Immunopathology; Lung; MERS-CoV infection.
. 2021 Jul 7.
doi: 10.1007/s10875-021-01061-z. Online ahead of print.
Elevated Expression Levels of Lung Complement Anaphylatoxin, Neutrophil Chemoattractant Chemokine IL-8, and RANTES in MERS-CoV-Infected Patients: Predictive Biomarkers for Disease Severity and Mortality
Maaweya E Hamed[SUP] 1 [/SUP], Asif Naeem[SUP] 2 [/SUP], Haitham Alkadi[SUP] 2 [/SUP], Aref A Alamri[SUP] 3 [/SUP], Ahmad S AlYami[SUP] 4 [/SUP], Abdullah AlJuryyan[SUP] 4 [/SUP], Wael Alturaiki[SUP] 5 [/SUP], Mushira Enani[SUP] 6 [/SUP], Samia T Al-Shouli[SUP] 7 [/SUP], Abdullah M Assiri[SUP] 8 [/SUP], Bandar Alosaimi[SUP] 9 [/SUP]
Affiliations
- PMID: 34232441
- DOI: 10.1007/s10875-021-01061-z
Abstract
The complement system, a network of highly-regulated proteins, represents a vital part of the innate immune response. Over-activation of the complement system plays an important role in inflammation, tissue damage, and infectious disease severity. The prevalence of MERS-CoV in Saudi Arabia remains significant and cases are still being reported. The role of complement in Middle East Respiratory Syndrome coronavirus (MERS-CoV) pathogenesis and complement-modulating treatment strategies has received limited attention, and studies involving MERS-CoV-infected patients have not been reported. This study offers the first insight into the pulmonary expression profile including seven complement proteins, complement regulatory factors, IL-8, and RANTES in MERS-CoV infected patients without underlying chronic medical conditions. Our results significantly indicate high expression levels of complement anaphylatoxins (C3a and C5a), IL-8, and RANTES in the lungs of MERS-CoV-infected patients. The upregulation of lung complement anaphylatoxins, C5a, and C3a was positively correlated with IL-8, RANTES, and the fatality rate. Our results also showed upregulation of the positive regulatory complement factor P, suggesting positive regulation of the complement during MERS-CoV infection. High levels of lung C5a, C3a, factor P, IL-8, and RANTES may contribute to the immunopathology, disease severity, ARDS development, and a higher fatality rate in MERS-CoV-infected patients. These findings highlight the potential prognostic utility of C5a, C3a, IL-8, and RANTES as biomarkers for MERS-CoV disease severity and mortality. To further explore the prediction of functional partners (proteins) of highly expressed proteins (C5a, C3a, factor P, IL-8, and RANTES), the computational protein-protein interaction (PPI) network was constructed, and six proteins (hub nodes) were identified.
Keywords: Chemokine; Complement system; Cytokine; Immunopathology; Lung; MERS-CoV infection.