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

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.

Figure 1

mHLA-DR expression in patients with hemophagocytic lymphohistiocytosis (HLH), healthy children (HC), and septic shock (SS). Only the first mHLA-DR value was retained for each patient. Values of mHLA-DR from HC and patients with SS originated from a previous study conducted in our institution [NCT02848144 (14)]. mHLA-DR expression corresponds to the number of antibodies bound per cell (AB/C). Wide lines correspond to the median value and narrow lines to first and third quartiles. Median age of HC was 2.8 years old [IQR (1.5–5.9)], and median age of SS children was 2.4 years old [IQR (0.4–4.4)]. Dots correspond to individual values. *** p<0.01, **** p<0.001.

Figure 2

Evolution of mHLA-DR (A) and ferritin (B) of patients with sHLH between day 0 (before corticosteroid initiation) and days 2 to 4 (after corticosteroid treatment). Discontinuous lines link values from each individual patient. The gray ribbon corresponds to the laboratory normal values for mHLA-DR and ferritine (mHLA-DR: 15,000–43,000 AB/C).

Figure 3

Course of Patient 1. Red dots and line correspond to mHLA-DR; the red ribbon corresponds to normal values. The gray dots and discontinuous line correspond to ferritin; the gray ribbon corresponds to normal values with an upper threshold of 500 µg/L. Each corticosteroid (CS) pulse arrow corresponds to methylprednisolone at 10mg/kg. The start of a new episode is defined by the relapse of sHLH symptoms and laboratory criteria.