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Circulating Immature Granulocytes With T-Cell Killing Functions Predict Sepsis Deterioration*

Guérin, Estelle MD; Orabona, Marie MD; Raquil, Marie-Astrid MD, PhD; Giraudeau, Bruno MD, PhD; Bellier, Rémy MD; Gibot, Sébastien MD, PhD; Béné, Marie-Christine MD, PhD; Lacombe, Francis MD, PhD; Droin, Nathalie PhD; Solary, Eric MD, PhD; Vignon, Philippe MD, PhD; Feuillard, Jean MD, PhD; François, Bruno MD

doi: 10.1097/CCM.0000000000000344
Clinical Investigations

Objectives: Primary objective was to identify leukocyte subsets that could predict the early evolution of sepsis at 48 hours (i.e., deterioration or stability/improvement). Secondary objectives were to evaluate the prognostic value of leukocyte subsets on mortality and immunosuppressive properties of immature granulocytes.

Design: Twenty-three peripheral blood leukocyte subsets were analyzed using a new-generation 10-color flow cytometry. T-cell killing activity of immature granulocytes was explored using a sorting method specifically developed.

Setting: ICUs and emergency departments.

Patients: All patients admitted to emergency department and ICU for sepsis ongoing for less than 24 hours were eligible. Exclusion criteria were pregnancy, age less than 18 years, solid tumors, HIV infection, hematological or inflammatory conditions, and immunosuppressive drugs. Finally, 177 patients were included.

Interventions: None.

Measurements and Main Results: The two most salient features of sepsis were decreased CD10 (CD10dim) and CD16 (CD16dim) expressions on granulocytes. With a threshold of 90% of CD10dim and 15% of CD16dim granulocytes, these immunophenotypic features, which are those of immature granulocytes, predicted sepsis deterioration at 48 hours with a sensitivity of 57% and 70% and a specificity of 78% and 82%, respectively. Survival rate at day 30 was 99% for patients without CD10dim and CD16dim, 85% for patients with increased CD16dim only, and 63% for patients with increased CD16dim and CD10dim granulocytes (p < 0.001). Among CD16dim immature granulocytes, we identified a CD14neg/CD24pos myeloid-derived suppressor cell subset with the capability of killing activated T cells. Consistently, an excess of CD16dim immature granulocytes was associated with both CD3 and CD4 T-cell lymphopenia in deteriorating patients.

Conclusions: Circulating immature granulocytes predicted early sepsis deterioration and were enriched in myeloid-derived suppressor cells which could be responsible for immunosuppression through the induction of T-cell lymphopenia.

Supplemental Digital Content is available in the text.

1Hematology Laboratory, Dupuytren University Hospital, Limoges, France.

2Intensive Care Unit, Dupuytren University Hospital, Limoges, France.

3Inserm UMR1009, Paris-Sud University, Gustave Roussy Institute, Villejuif, France.

4Inserm CIC-P 0202, Tours Regional University Hospital, François Rabelais, University, Tours, France.

5Intensive Care Unit, Central Hospital, Nancy, France.

6Immunology Laboratory, Brabois University Hospital, Nancy, France.

7Hematology Laboratory, Haut-Lévêque University Hospital, Pessac, France.

8Inserm CIC-P 0801, Dupuytren University Hospital, Limoges, France.

* See also p. 2135.

This study was performed at CHU Dupuytren Limoges.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by “Recherche clinique translationnelle Inserm/DHOS, 2010.”

Dr. Béné received grant support (grant of the project: part of the Programme Hospitalier de Recherche clinique [PHRC]). Her institution received grant support from PHRC and Programme de Soutien aux Techniques Innovantes. Dr. Lacombe consulted for Horiba Medical and received support for development of educational presentations from Bioformation. His institution received grant support from PHRC and Beckman Coulter. Dr. Solary’s institution received grant support from Institut National de la Santé et de la Recherche Médicale (National funding of the research unit), French national agencies (Agence National de Recherche, Institut National du Cancer), and charities (Ligue Nationale Contre le Cancer, Fondation Association pour la Recherche sur le Cancer) (grants supporting our various research projects). He and his institution received support for development of educational presentations from European School of Hematology, Novartis, and Sanofi (lectures on hematological diseases [education meetings]). Dr. Feuillard’s institution received grant support from the “PHRC” French Government National Program. Dr. François served as board member for KentaBiotech; consulted for KentaBiotech, GlaxoSmithKline, Sanofi, and Medimmune; and received support for development of educational presentations from Sanofi. His institution received grant support from Biomérieux. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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