These conclusions are based on the multilevel approach of the current study; at first, comparisons between SIRS, sepsis, severe sepsis and septic shock indicated that septic shock is the stage of critical illness with the lower circulating IgM; then measurements at distinct time points that is, upon initial diagnosis and upon worsening showed that circulating IgM decreases specifically upon progression from severe sepsis to septic shock; and finally, intense monitoring of IgM after the start of vasopressors revealed a relationship between lacking distribution of IgM and unfavorable prognosis. Here, CD40LG is linked to systemic inflammatory response syndrome.