Laboratory parameters identify familial haemophagocytic lymphohistiocytosis from other forms of paediatric haemophagocytosis

Abstract

SummaryHaemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune dysregulation and is classified as primary or secondary according to the underlying aetiology. The treatment strategies recommended for these two groups differ substantially; however, it is thought to be impossible to predict the underlying causes of HLH using conventional laboratory tests. Recent studies show that serum levels of soluble interleukin-2 receptor (sIL2R) and ferritin are useful for differentiating some forms of HLH. The present study reports that combinations of common laboratory parameters, such as the percentage of total lymphocytes within the peripheral blood leucocyte population, serum levels of lactate dehydrogenase and the sIL2R/ferritin ratio, are useful for identifying patients with familial haemophagocytic lymphohistiocytosis and for differentiating the underlying aetiology of paediatric HLH during the early course of the disease. These findings suggest that the pathogenesis of HLH differs greatly in terms of innate and adaptive immunity depending on the aetiology and may provide a new approach to unravelling the complex pathophysiology underlying this syndrome.

Malignancy-associated hemophagocytic lymphohistiocytosis in children: a 10-year experience of a single pediatric hematology center

“…In addition, the HScore designed by Fardet [23] appeared to be more sensitive in early diagnosis of adult HLH. Other laboratory parameters, such as TNF-α, IFN-γ, IL-6 and presepsin, are helpful in distinguishing M-HLH from others [24,25]. In our study, a ferritin level of over 10000 ng/mL was found in 20 of 26 patients, while sCD25/ferritin ratio>2 was found in 5 of 7 patients.…”

Mouse Cytomegalovirus Infection in BALB/c Mice Resembles Virus-Associated Secondary Hemophagocytic Lymphohistiocytosis and Shows a Pathogenesis Distinct from Primary Hemophagocytic Lymphohistiocytosis

“…Our observations with respect to the HLH mouse model in the absence of IFN-g are of clinical relevance because, recently, a first report appeared on two IFN-gR-deficient patients who acquired HLH after herpesvirus and mycobacterial infection (63). In these patients, the syndrome must have developed in an IFN-g-independent way, arguing against the existence of a general pathogenic pathway that would cause both primary and secondary HLH (19,64). Alternative pathways, also IFN-g-independent ones (13,18,65), are capable of inducing a similar syndrome.…”

Comparison of Th1/Th2 cytokine profiles between primary and secondary haemophagocytic lymphohistiocytosis

“…In this cohort, all primary HLH cases belong to type2 HLH including FHL2 and XLP1, and it is not surprising that we can not find difference of degranulation between primary HLH and secondary HLH groups. Yasumi et al proposed that the percentage of total lymphocytes, serum levels of LDH, and the sIL2R/ferritin ratio could differentiate familial from secondary HLH [ 32 ]. In this study, when we compare to the secondary HLH patients, primary HLH patients have higher percentage of lymphocytes (mean level 75.3 % vs 48.0 %, P = 0.012), and lower percentage of neutrophils (12.8 % vs 40.7 %, P = 0.012), which is consistent with Yasumi et al’s findings.…”