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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

Keywords: RCS; S100A8/9; diagnosis; phagocytic lymphohistiocytosis; prognosis.

FIGURE 1

Correlation between variables: Significance of correlation between variables is indicated by “*”for P < 0.05 and “**” for P < 0.01, the darker the color, the stronger the correlation.

FIGURE 2

Comparison of S100A8/9 levels in patients with secondary hemophagocytic lymphohistiocytosis (sHLH) vs. healthy controls and lymphoma patients: (A) Comparison of S100A8/9 levels in 48 patients with sHLH vs. 21 healthy controls; (B) Grouping of patients with sHLH according to different aetiologies and comparison of S100A8/9 levels between the groups; (C) Comparison of S100A8/9 levels between 32 patients with LHLH vs. S100A8/9 levels in 16 patients with non-LHLH. Note: AHLH is rheumatology-associated HLH, IHLH is infection-associated HLH, LHLH is lymphoma-associated HLH, and non-LHLH is non-lymphoma-associated HLH.

FIGURE 3

(A) ROC curve of S100A8/9 for the comparison between sHLH patients (n = 48) vs. normal people (n = 21); (B) ROC curve of S100A8/9 for the comparison between LHLH (n = 32) vs. non–LHLH patients (n = 16); (C) ROC curve of sHLH patients (n = 48) for the comparison between S100A8/9 levels vs. HScore.

FIGURE 4

(A) The relationship between S100A8/9 and status in 45 sHLH patients was analyzed using a restricted cubic spline regression model. The data were fitted using a restricted cubic spline Cox proportional risk regression model adjusted for sex, age, and ferritin according to the S100A8/9 adjusted state risk ratio of 0.809, with the model 4–noded at the 5th, 35th, 65th, and 95th percentiles for S100A8/9 0.809 (reference value of 2.44). Solid lines indicate HRs and shaded shapes indicate 95% CIs. HR, hazard ratio; CI, confidence interval; (B) Survival analysis of the high S100A8/9 expression group (>2.44 μg/mL, n = 22) vs. the low S100A8/9 expression group (≤2.44 μg/m, n = 23) in patients with sHLH.

FIGURE 5

Comparison of mortality rates between high S100A8/9 expression group (>2.44 μg/mL, n = 22) and low S100A8/9 expression group (≤2.44 μg/mL, n = 23). (A) Comparison of mortality rates in January, (B) comparison of mortality rates in March mortality, (C) comparison of mortality rates in 1–year, (D) comparison of mortality rates in 3–years mortality.