These findings strongly support the incorporation of serology into diagnostic algorithms for timely diagnosis and proper management of STEC-HUS patients.<h4>Importance</h4>This study evaluated, for the first time, the dynamics of serogroup-specific IgM and IgG anti-O polysaccharide antibody response in 55 Shiga toxin-producing <i>Escherichia coli</i>-associated hemolytic uremic syndrome (STEC-HUS) pediatric patients. The gene discussed is CD40LG; the disease is hemolytic-uremic syndrome.