title: Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients.
abstract: Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.
  
  
  
  Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time.
  
  
  
  At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)).
  
  
  
  None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients.
authors.affiliation: HIV/Hepatitis Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia; Université Paris Diderot-Paris 7, Sorbonne Paris-Cité, Paris, France.
authors.forename: Janin
authors.initials: J
authors.lastname: Nouhin
authors.affiliation: Immunology Platform, Pasteur Institute in Cambodia, Phnom Penh, Cambodia.
authors.forename: Polidy
authors.initials: P
authors.lastname: Pean
authors.affiliation: Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Madec
authors.affiliation: Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France.
authors.forename: Mathieu F
authors.initials: MF
authors.lastname: Chevalier
authors.affiliation: Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Didier
authors.affiliation: Epidemiology and Public Health Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Borand
authors.affiliation: Institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Blanc
authors.affiliation: Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.affiliation: Infectious and Tropical Diseases Department, University Hospital, Nîmes, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Laureillard
authors.affiliation: Unité "Régulation des Infections Rétrovirales", Institut Pasteur, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Paris, France; Université Paris Descartes, Sorbonne Paris-Cité, Paris, France. Electronic address: laurence.weiss@aphp.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000097:blood / Q000150:complications / Q000175:diagnosis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D014376:Tuberculosis / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers; D053590:Interleukin 1 Receptor Antagonist Protein
keywords: Anti-tuberculosis treatment; Biomarkers; Cambodia; HIV/tuberculosis co-infection; IL-1 receptor antagonist; TB-IRIS