Original Sins of Immunoglobulins in Sepsis

IVIG content in Ig isotypes could influence therapeutical results. This way, IgM-enriched IVIG could render more benefits in terms of survival than those preparations containing just IgG. Another major issue is the absence of evidence characterising the primary therapeutic principles in IVIG (Fab elements ?, Fc fragments ?) which could have potentially beneficial effects in sepsis (toxin scavenging, antibacterial effect, and immunomodulation). Moreover, the concentration and antimicrobial specificities of the antibodies contained in the IVIG preparations are not taken sufficiently into account. These are highly dependent on the personal antecedents of natural infections and vaccination of the blood donors for IVIG, who are healthy individuals. In consequence, IVIG could be deficient in antibodies against microbes causing hospital-acquired infections. Developing new IVIG preparations obtained from pools of sera of survivors to sepsis of either community or nosocomial origin could solve this problem. In addition, taking into account the age of the blood donors could be important for understanding the biological properties of IVIG since the natural IgG Ig repertoire is highly dependent on age.

There is probably a 'window of opportunity' for IVIG in the first days that follow clinical presentation of sepsis. If this window is missed, probabilities of success could be greatly diminished. In addition, monitoring Ig levels along the course of the treatment would help us to understand the pharmacokinetics of IVIG in patients with sepsis which is relevant for further dosage calculation. In turn, it is unknown whether the main goal of IVIG in sepsis has to be to refill low levels of endogenous Igs or alternatively whether IVIG could exert a beneficial effect independently of these levels.