# Expression and clinical significance of S100A8/9 in adults with secondary phagocytic lymphohistiocytosis

**Authors:** Ziwei Fang, Xin Gao, Limin Duan, Jujuan Wang, Tian Tian, Ji Xu, Yongqian Shu, Guangli Yin, Hongxia Qiu

PMC · DOI: 10.3389/fmolb.2025.1607352 · 2025-07-15

## TL;DR

This study shows that S100A8/9 levels in blood can help diagnose and predict outcomes in patients with a rare inflammatory disease called secondary phagocytic lymphohistiocytosis.

## Contribution

The study identifies S100A8/9 as a potential biomarker for diagnosing and predicting prognosis in sHLHa patients.

## Key findings

- Serum S100A8/9 levels were higher in sHLHa patients compared to healthy controls.
- High S100A8/9 levels and low ANC were independent risk factors for poor prognosis in sHLHa patients.
- S100A8/9 levels showed a nonlinear correlation with survival and a threshold effect at 2.44 µg/mL.

## Abstract

The study aimed to investigate the diagnostic and prognostic value of serum S100A8/9 levels with sHLHa, a high-mortality multiorgan inflammatory syndrome with no reliable clinical biomarkers, where calreticulin’s role is unclear.

This was a study of 67 newly diagnosed sHLHa patients. 48 patients met criteria and were analyzed. ELISA detected S100A8/9 levels in patients and controls. The optimal classification threshold for S100A8/9 was determined to be 2.44 µg/mL by restricted cubic spline (RCS) curve analysis. Patients were categorized. Correlations, diagnostic efficacy, survival differences, and prognosis impacts were analyzed.

Serum S100A8/9 levels in sHLHa patients were greater than in healthy controls. Various analyses showed its diagnostic and prognostic value. ANC<1.0 × 109/L and high S100A8/9 expression group were independent risk factors for poor prognosis in patients with sHLHa. It’s correlated with liver function indicators and HScore.

This study evaluates S100A8/9 in sHLHa diagnosis and prognosis. S100A8/9 levels are useful for differentiating patients, providing etiologic and survival info. They show a nonlinear positive correlation with survival and a threshold effect. Serum S100A8/9 levels offer potential biomarkers, and further studies are needed.

## Full-text entities

- **Genes:** CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IGF1R (insulin like growth factor 1 receptor) [NCBI Gene 3480] {aka CD221, IGFIR, IGFR, JTK13}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, ECSIT (ECSIT signaling integrator) [NCBI Gene 51295] {aka SITPEC}, CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}
- **Diseases:** phagocytic (MESH:D010585), NK/T-cell lymphomas (MESH:D016399), cirrhosis (MESH:D005355), liver injury (MESH:D017093), infection (MESH:D007239), SLE (MESH:D008180), cancers (MESH:D009369), inflammatory (MESH:D007249), rheumatologic immune (MESH:D007154), chronic lymphocytic leukemia (MESH:D015451), peripheral T-cell lymphoma (MESH:D016411), Fever (MESH:D005334), lymphoma (MESH:D008223), multiorgan inflammatory syndrome (MESH:D018746), cytokine storm (MESH:D000080424), rheumatology (MESH:D012216), liver damage (MESH:D056486), liver disease (MESH:D008107), B-cell lymphomas (MESH:D016393), MAS (MESH:D005359), diffuse large B-cell lymphomas (MESH:D016403), sepsis (MESH:D018805), death (MESH:D003643), hepatosplenomegaly (MESH:C535727), methemoglobinemia (MESH:D008708), lung injury (MESH:D055370), lung, liver, colorectal, (MESH:D015179), ENKL (MESH:D054391), multiorgan dysfunction (MESH:D009102), associated (MESH:D018886), autoimmune disorders (MESH:D001327), AHLH (MESH:D051359), COVID-19 (MESH:D000086382), rheumatoid arthritis (MESH:D001172)
- **Chemicals:** methyl-beta-cyclodextrin (MESH:C108732), LPS (MESH:D008070), lipid (MESH:D008055), Sulfonamides (MESH:D013449), TG (MESH:D014280), ABR2527 (-), EDTA (MESH:D004492)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676]
- **Mutations:** AUC of 0, V140A

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12304547/full.md

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Source: https://tomesphere.com/paper/PMC12304547