Elevated monocyte HLA-DR in pediatric secondary hemophagocytic lymphohistiocytosis: a retrospective study

Sylvain Raimbault; Guillaume Monneret; Morgane Gossez; Fabienne Venet; Alexandre Belot; Franck Zekre; Solene Remy; Etienne Javouhey

doi:10.3389/fimmu.2023.1286749

Elevated monocyte HLA-DR in pediatric secondary hemophagocytic lymphohistiocytosis: a retrospective study

Front Immunol. 2023 Nov 24:14:1286749. doi: 10.3389/fimmu.2023.1286749. eCollection 2023.

Authors

Sylvain Raimbault¹, Guillaume Monneret², Morgane Gossez², Fabienne Venet², Alexandre Belot³, Franck Zekre³, Solene Remy¹, Etienne Javouhey¹

Affiliations

¹ Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de Réanimation Pédiatrique, Bron, France.
² Hospices Civils de Lyon, Hôpital Edouard Herriot, Laboratoire d'Immunologie, Lyon, France.
³ Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de Néphrologie et Rhumatologie Pédiatrique, Centre de Référence RAISE (Rhumatismes Inflammatoires et Maladies Auto-Immunes Systémiques Rares de l'Enfant), ERN RITA (European Reference Network for Immunodeficiency, Autoinflammatory, Autoimmune and Paediatric Rheumatic Diseases), Bron, France.

Abstract

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition, and its diagnosis may be challenging. In particular, some cases show close similarities to sepsis (fever, organ failure, and high ferritin), but their treatment, while urgent, differ: prompt broad-spectrum antibiotherapy for sepsis and immunosuppressive treatment for HLH. We questioned whether monocyte human leucocyte antigen (mHLA)-DR could be a diagnostic marker for secondary HLH (sHLH).

Methods: We retrospectively reviewed data from patients with a sHLH diagnosis and mHLA-DR quantification. mHLA-DR data from healthy children and children with septic shock, whose HLA-DR expression is reduced, from a previously published study were also included for comparison.

Results: Six patients with sHLH had mHLA-DR quantification. The median level of monocyte mHLA-DR expression in patients with sHLH [79,409 antibodies bound per cell (AB/C), interquartile range (IQR) (75,734-86,453)] was significantly higher than that in healthy children and those with septic shock (29,668 AB/C, IQR (24,335-39,199), and 7,493 AB/C, IQR (3,758-14,659), respectively). Each patient with sHLH had a mHLA-DR higher than our laboratory normal values. Four patients had a second mHLA-DR sampling 2 to 4 days after the initial analysis and treatment initiation with high-dose corticosteroids; for all patients, mHLA-DR decreased to within or close to the normal range. One patient with systemic juvenile idiopathic arthritis had repeated mHLA-DR measurements over a 200-day period during which she underwent four HLH episodes. mHLA-DR increased during relapses and normalized after treatment incrementation.

Conclusion: In this small series, mHLA-DR was systematically elevated in patients with sHLH. Elevated mHLA-DR could contribute to sHLH diagnosis and help earlier distinction with septic shock.

Keywords: cytokine storm; hemophagocytic lymphohistiocytosis; lymphocyte activation; macrophage activation syndrome; monocyte HLA-DR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Female
HLA-DR Antigens
Humans
Lymphohistiocytosis, Hemophagocytic* / diagnosis
Monocytes
Retrospective Studies
Sepsis* / metabolism
Shock, Septic*

Substances

HLA-DR Antigens

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was supported by the institution employing the authors, as part of their usual duties.