Comprehensive analyses of immunoglobulin proteome and clinical variables identify biomarkers to predict mortality in patients with influenza-associated lower respiratory tract infection

Background: Influenza-associated lower respiratory tract infection (I-LRTI) brings a heavy clinical burden, and clinicians lack an effective prognostic evaluation system to control disease progression. Methods: This was a prospective, observational study, and the endpoint was 28-day mortality. Plasma microarrays were used for quantitative analysis of immunoglobulin (Ig) and its subclasses. Prognostic factors from Ig and clinical variables in the patients with I-LRTI were identified to create a prediction model. Results: To address this issue, we prospectively and observationally studied the difference of immunoglobulin proteome and clinical variables between survivors and non-survivals in 107 patients with influenza-associated lower respiratory tract infection (I-LRTI) selected from four hospitals affiliated to Capital Medical University. The results identified 17 variables with significant or marginally statistical differences by univariate analysis, including lymphocyte count (LY), monocytes count (MO), CD3 + CD4 + T-cell count, CD3 + CD8 + T-cell count, IgA, IgA1, IgG2, IgG4, CRP, PCT, D-dimer, oxygenation index, glycosylated hemoglobin, lactic acid (LAC), base excess of blood, lactic dehydrogenase, and α-hydroxybutyrate dehydrogenase. Furthermore, we analyzed the correlations of all the variables by hierarchical clustering analysis in which different functional modules were formed between survival and non-survival groups that are associated with the immunity and severe infection. At last, we built a prediction model with nine variables (D-dimer, days from onset to ED, IgA, IgG2, LAC, LY, MO, Staphylococcus aureus co-infection and age), with which the AUC value of 0.810 (95% CI 0.755-0.839) was achieved with the evaluation of LOO cross validation. The predictive model was further validated by disease severity evaluation. Conclusion: Lethal bacterial (especially S. aureus ) co-infection was associated with cellular immunity, oxygenation index, HbA1C and age. The combined prediction model with D-dimer, Days from onset to ED, IgA, IgG2, LAC, LY, MO, S.aureus co-infection and age demonstrate the predictive mortality powerfully in patients with I-LRTI.