# The performance of sCD25 and CTLs degranulation test for screening patients with primary hemophagocytic lymphohistiocytosis: a large-scale multicenter study in China

## TL;DR

This study evaluates the effectiveness of sCD25 and CTLs degranulation tests in diagnosing primary hemophagocytic lymphohistiocytosis in a large group of patients in China.

## Contribution

The study provides a large-scale validation of sCD25 and CTLs degranulation tests for pHLH screening and demonstrates improved accuracy when combining both tests.

## Key findings

- The CTLs degranulation test is more sensitive than sCD25 for identifying pHLH with degranulation pathway gene defects.
- Combining sCD25 and CTLs degranulation tests improves diagnostic accuracy with an AUC of 0.833.
- The sCD25 test has a sensitivity of 75.9% and specificity of 57.3% for pHLH with cytotoxic pathway gene defects.

## Abstract

Hemophagocytic lymphohistiocytosis can be classified as primary HLH (pHLH) and secondary HLH. The early identify of pHLH can facilitate successful treatment. The rapid screening test greatly facilitated the diagnostic process of pHLH. However, there are rare studies to explore the ability of sCD25 and cytotoxic T lymphocytes (CTLs) degranulation test to rapidly screen pHLH.

We validated the accuracies of sCD25 and CTLs degranulation test in screening pHLH in 1224 clinically confirmed or suspected HLH patients through calculating area under the curve (AUC) and diagnostic parameters at optimal threshold.

The sensitivities of sCD25 to identify pHLH with defects in cytotoxic pathway genes was 75.9%, with specificities of 57.3% and AUC of 0.640. The sensitivities of CTLs degranulation test to identify pHLH with defects in degranulation pathway genes was 87.0%, with specificities of 69.0% and AUC of 0.794. The sensitivities of combination of sCD25 and CTLs degranulation test to identify pHLH with defects in cytotoxic pathway genes was 90.0%, with specificities of 69.8% and AUC of 0.833.

For identifying pHLH, CTLs degranulation test is more sensitive and no less specific than sCD25 and the combination of sCD25 and CTLs degranulation test can improve the accuracy further.