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Key Points Germline activating STAT3 mutations were detected in 3 patients with autoimmunity, hypogammaglobulinemia, and mycobacterial disease. T-cell lymphoproliferation, deficiency of regulatory and helper 17 T cells, natural killer cells, dendritic cells, and eosinophils were common.

BackgroundEarly diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.MethodsThe study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).ResultsThe median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.ConclusionsA high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.

Abstract. Uusitalo-Seppälä R, Huttunen R, Tarkka M, Aittoniemi J, Koskinen P, Leino A, Vahlberg T, Rintala EM (Satakunta Central Hospital, Pori; Tampere University Hospital, Tampere; University of Tampere Medical School, University of Tampere, Tampere; Centre for Laboratory Medicine, Pirkanmaa Hospital District, Tampere; Turku University, Turku; Turku Univeristy Hospital, Hospital District of Southwest Finland, Turku; Turku University, Turku, Finland). Soluble urokinase-type plasminogen activator receptor in patients with suspected infection in the emergency room: a prospective cohort study. J Intern Med 2012; 272: 247-256.Objectives. The soluble form of urokinase-type plasminogen activator (suPAR) was evaluated as an early prognostic marker of sepsis in patients with suspected infection.Design. A single-centre prospective cohort study.Methods. Thecohortcomprised539patientsintheemer-gency department with suspected infection: 59 without systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 68 with bacterial infection and without SIRS (group 2), 54 with SIRS and without bacterial infection (group 3), 309 with sepsis (SIRS and bacterial infection) and without organ failure (group 4)and49with severe sepsis (SIRS, bacterial infection and organ failure) (group 5). suPAR was measured on admission using a commercial solid-phaseenzyme-linkedimmunosorbentassay.Results. The median soluble form of the receptor (suPAR) concentrations in groups 1-5 were 4.7, 5.0, 4.4, 4.8 and 7.9 ng mL À1, respectively (P < 0.001). The levels were significantly higher in nonsurvivors compared with survivors (8.3 vs. 4.9 ng mL À1 , P < 0.001) and in patients with severe sepsis (group 5) compared with those in the other groups (7.9 vs. 4.8 ng mL , suPAR had 76% sensitivity and 69% specificity for fatal disease; at a cut-off level of 6.6 ng mL À1 , the sensitivity and specificity for severe sepsis were 67% and 72%, respectively. In multivariate models, high suPAR remained an independent predictor of case fatality and severe sepsis after adjusting for potential confounders. Conclusions.A high suPAR level predicts case fatality and severe sepsis in patients with suspected infection.

PCT and IL-6 proved superior to CRP in detecting patients with severe sepsis. The findings thus support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis. The automatic ECLIA method allows even night-shift measurements.

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There is an increasing need for novel biomarkers that enable better diagnostic and prognostic stratification of patients with suspected infection. A proprotein convertase enzyme FURIN is upregulated upon immune cell activation, and it promotes infectivity by cleaving and activating pathogens. In this study, we determined FURIN levels in plasma using ELISA from 537 patients that were admitted to emergency room with suspected infection. Patients were sorted to high-and low-level FURIN groups with a cut-off level of 370 pg/ml. The study cohort included five diagnostic groups: Group 1, no systemic inflammatory response syndrome (SIRS, n = 59 patients); Group 2, bacterial infection without SIRS (n = 67); Group 3, SIRS, but no bacterial infection (n = 308); Group 4, sepsis without organ failure (n = 308); and Group 5, severe sepsis (n = 49). Statistically significant associations were not found between the plasma level of FURIN and the prevalence of sepsis (P = 0.957), diagnostic group of a patient (P = 0.737) or the bacteria in blood culture (P = 0.499). Additionally, the concentration of FURIN did not predict the severity or case fatality of the infectious disease. However, statistically significant associations were found between high plasma level of FURIN and diagnosed rheumatic disease (P < 0.001) as well as with the prevalence of non-smokers (P = 0.034). Thus, albeit the plasma level of FURIN does not predict the severity of infectious disease, it may be of use in the diagnostics of autoimmune diseases.

PLA(2)GIIA seemed to be superior to CRP, BPI, and WBC in differentiating patients with severe sepsis. BPI gave no additional information in this respect.