The influence of endogenous levels of Igs on prognosis remains unclear. Whereas the SBITS (Score-Based Immunoglobulin Therapy of Sepsis) study [
8] did not show any negative influence of a low IgG level on 28-day mortality [
2], Taccone and colleagues [
9] found that patients with community-acquired septic shock and hypo-IgG had higher mortality. Similarly, Průcha and colleagues [
10] reported the presence of IgG hypogammaglobulinemia in patients with severe sepsis as an independent factor of mortality. In turn, we have recently demonstrated the existence of a statistical association between low endogenous levels of Igs and poor outcome in severe sepsis and septic shock [
4]. Differences among studies could be explained in part by the different composition of the patient cohorts. In the SBITS study, percentile 25 for IgG distribution was 610 mg/dL, whereas in our study it was 374 mg/dL, probably because of a higher frequency of patients with prior immunosuppressive conditions in our cohort (Werdan K, personal communication). Although it remains to be elucidated whether low levels of endogenous Igs are a marker of disease severity rather than a cause of mortality, our opinion is that it is a potential confounding factor that has to be taken into account in the IVIG trials. In addition, the distinct Ig subclasses and isotypes (IgG1, IgM, and IgA) have a different influence on prognosis in sepsis [
4]. Combined deficits of these isotypes are associated with higher risk of mortality [
4]. Assessing levels of basal Ig isotypes could help us to understand the potential effect of IVIG preparations containing only IgG and of those enriched in IgM or IgA or both. It could be also important to evaluate the presence/absence of pre-existing specific antibodies against the microbe causing the septic insult [
11].