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Thank you for the opportunity to respond to the letter by Karatzas et al. [1] commenting on our recent paper concerning the effects of IgM-enriched immunoglobulin preparations in severe sepsis [2].  It was mentioned in the letter that the study protocol of Karatzas et al. regarding the design and inclusion criteria (except the age) was similar to our study design. It seems that there is another important difference between two studies, which is the subgroup analysis. Because of the limited number of patients included in our study, it was not intended to focus on the role of immunotherapy in reducing the mortality rate of severe sepsis patients. Mortality rate analyses in the subgroups of patients with different admission Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were therefore not performed in our study.  As Karatzas et al. noted, the APACHE II scores of our patients were lower than those found in their preliminary data analysis. This is an important difference indicating that the patient populations of their study and our study are far beyond similarity.  Neurological evaluation in APACHE II scoring is based on the Glasgow coma scale (GCS) and is usually complicated by the frequent use of sedative agents in critically ill patients. It is often not clear whether to assume GCS in the absence of sedative drugs or to consider the actual GCS of the patient. Certainly this computation might be very confusing and prone to errors in data collection. In our clinical practice, we generally assume the mental state of the patients in the absence of sedative drugs while calculating the GCS. This might be the reason for relatively low levels of APACHE II scores in our study population. We agree with Karatzas et al. that the interpretation of data could be more relevant by homogenising the patients according to some clinical characteristics, especially in larger studies investigating the beneficial effects of immunotherapy in septic patients.  Our study, which is the initial step of a new series of clinical investigations on this subject, was performed in a small group of patients with severe sepsis. We mentioned in our paper that recruiting this number of patients could confirm a change in severity and mortality of sepsis with the administration of IgM-enriched immunoglobulin preparations.  As we pointed out in our paper, we think that in addition to investigating subgroups of septic patients, further studies should focus on laboratory and clinical measures to identify patients who might benefit from specific immunomodulatory therapies.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis: another point of view – authors' response