CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome
Por:
Choreno-Parra, Jose Alberto, Jimenez-Alvarez, Luis Armando, Ramirez-Martinez, Gustavo, Sandoval-Vega, Montserrat, Salinas-Lara, Citlaltepetl, Sanchez-Garibay, Carlos, Luna-Rivero, Cesar, Hernandez-Montiel, Erika Mariana, Fernandez-Lopez, Luis Alejandro, Cabrera-Cornejo, Maria Fernanda, Choreno-Parra, Eduardo Misael, Cruz-Lagunas, Alfredo, Dominguez, Andrea, Marquez-Garcia, Eduardo, Cabello-Gutierrez, Carlos, Bolanos-Morales, Francina Valezka, Mena-Hernandez, Lourdes, Delgado-Zaldivar, Diego, Rebolledo-Garcia, Daniel, Guadarrama-Ortiz, Parmenides, Regino-Zamarripa, Nora E., Mendoza-Milla, Criselda, Garcia-Latorre, Ethel A., Rodiguez-Reyna, Tatiana Sofia, Cervantes-Rosete, Diana, Hernandez-Cardenas, Carmen M., Khader, Shabaana A., Zlotnik, Albert, Zuniga, Joaquin
Publicada:
26 feb 2021
Resumen:
The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid
cells, exhibits bactericidal activity, and exerts anti-viral functions.
This chemokine is constitutively expressed in the respiratory tract,
suggesting a role in lung defenses. However, little is known about the
participation of CXCL17 against relevant respiratory pathogens in
humans. Here, we evaluated the serum levels and lung tissue expression
pattern of CXCL17 in a cohort of patients with severe pandemic influenza
A(H1N1) from Mexico City. Peripheral blood samples obtained on admission
and seven days after hospitalization were processed for determinations
of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The
expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung
autopsy specimens from patients that succumbed to the disease. Serum
CXCL17 levels were also analyzed in two additional comparative cohorts
of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB)
patients. Additionally, the expression of CXCL17 was tested in lung
autopsy specimens from COVID-19 patients. A total of 122 patients were
enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24
had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung
specimens from patients that died of pandemic influenza A(H1N1) and
COVID-19. Interestingly, serum levels of CXCL17 were increased only in
patients with pandemic influenza A(H1N1), but not COVID-19 and PTB.
CXCL17 not only differentiated pandemic influenza A(H1N1) from other
respiratory infections but showed prognostic value for
influenza-associated mortality and renal failure in machine-learning
algorithms and regression analyses. Using cell culture assays, we also
identified that human alveolar A549 cells and peripheral blood
monocyte-derived macrophages increase their CXCL17 production capacity
after influenza A(H1N1) pdm09 virus infection. Our results for the first
time demonstrate an induction of CXCL17 specifically during pandemic
influenza A(H1N1), but not COVID-19 and PTB in humans. These findings
could be of great utility to differentiate influenza and COVID-19 and to
predict poor prognosis specially at settings of high incidence of
pandemic A(H1N1). Future studies on the role of CXCL17 not only in
severe pandemic influenza, but also in seasonal influenza, COVID-19, and
PTB are required to validate our results.
Filiaciones:
Inst Politecn Nacl, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Lab Inmunobiol & Genet, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Mexico City, DF, Mexico
Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuropatol, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Pathol, Mexico City, DF, Mexico
Tecnol Monterrey, Escuela Med & Ciencias Salud, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Posgrad Ciencias Biol, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Dept Virol, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Subdirect Surg, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Dermatol, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Educ, Mexico City, DF, Mexico
Ctr Especializado Neurocirugia & Neurociencias Me, Mexico City, DF, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico
Inst Nacl Enfermedades Resp Ismael Cosio Villegas, Resp Crit Care Unit, Mexico City, DF, Mexico
Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
Univ Calif Irvine, Sch Med, Dept Physiol & Biophys, Inst Immunol, Irvine, CA 92717 USA
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