In particular, we would like to acknowledge Matt P

In particular, we would like to acknowledge Matt P. levels did not differ significantly for culture-positive (CP) compared with culture-negative (CN, no organism found) sepsis samples. KaplanCMeier analysis was used to compare survival curves according to IgM levels, with no significant difference. We observed significantly higher survival in the CP samples when comparing with CN. Cut-off value for IgM (266 g/mL) for diagnosis of sepsis patients was determined using receiver operator characteristic (ROC) curves with 70% sensitivity, 69% specificity and 92% negative predictive values (NPV), respectively. The corresponding area under the curve (AUC) for the discrimination of sepsis patients was AUC = 0.73, and in a subgroup analysis of CP was AUC = 0.77 and for CN was AUC = 0.79. We confirm IgM as a good diagnostic marker of sepsis. These findings indicate a difference in the pathology between culture-positive versus negative sepsis, SIRS and survival. This indicates that IgM is likely relevant to pathology, because of its role in the early immune response against pathogens, the potentially protective JNJ7777120 role of natural IgM antibodies, and supports its application in immunoglobulin therapy. Keywords: immunoglobulins, sepsis, SIRS, culture-negative 1. Introduction Sepsis is defined as the dysregulated host response to infection causing organ dysfunction [1]. This recent definition closely mirrors the previous category of severe sepsis, which is a major cause of morbidity and mortality in both developed and developing countries [2]. Mortality rates remain at around 30%, and higher in septic shock, despite advances in critical care [3]. The invasion of sterile tissues by infective agents will trigger a primarily innate immune response, which could lead to the clinical manifestation of sepsis and severe sepsis pathology [4]. Initially, it was assumed that this was primarily due to Gram-negative bacteria, but it is now clear that Gram-positive bacteria, as well as viral, fungal and parasitic organisms, also play an important role in the development of sepsis [5,6,7,8]. A retrospective, longitudinal study over a 20-year period reported that in JNJ7777120 over 50% of sepsis patients, microbiologically proven culture-positive (CP) samples were recorded [9] The invading organism distribution showed Gram-positive bacteria (52.1% of cases), Gram-negative bacteria (37.6%), polymicrobial infections (4.7%), anaerobes (1.0%), and fungi (4.6%) [9]. The organism class responsible for the primary infection, has been shown to play a role in determining the mortality of patients with sepsis. We have previously demonstrated that primarily JNJ7777120 Gram-negative infections are associated with an elevated mortality [8]. However, often no specific organism can be identified, and 28C49% of severe sepsis incidents have been described as JNJ7777120 being culture-negative (CN) [10,11]. This is commonly explained by a lack of test sensitivity for infecting organisms due to insensitive methodologies applied in the clinical practice or administration of antibiotics [12], but could also be a result of pathophysiological differences between culture-positive and negative sepsis or SIRS [13]. Low immunoglobulin levels have been found in sepsis [14,15,16,17,18]. Rabbit polyclonal to ABCG5 The IgM isotype is produced by B cells in responses to acute infection, thus endogenous IgM is the first line of the humoral host defense to aid opsonization and clearance of invading organisms [19,20,21]. IgM has been shown to be crucial for controlling both viral and bacterial infections [22,23,24], as its absence leads to inefficient induction of protective IgG antibody responses [25,26]. Low IgM levels have been shown to be associated with sepsis [27,28,29], possibly caused by a defective B cell response or a selective depletion of IgM producing memory cells [30,31], which may affect early pathogen clearance. Some evidence indicates that IgM-enriched therapy may be beneficial in Gram-negative sepsis, however the data is conflicting [32,33,34]. Unknown mechanisms of action of both endogenous immunoglobulins and immunoglobulin preparations in sepsis could explain the.