Rapid Detection of Inter-alpha Inhibitor Proteins in Neonatal Sepsis and Necrotizing Enterocolitis

Inter-alpha Inhibitor Proteins (IAIP) are serine protease inhibitors and a reliable inflammatory biomarker. We have demonstrated that IAIP levels decrease during sepsis in humans and animal models. Currently, enzyme-linked immunosorbent assay (ELISA) is the standard procedure to measure IAIP levels. We developed a lateral flow immunoassay (LFIA) that allows rapid, point of care detection. We compared IAIP levels in infants with sepsis and/or necrotizing enterocolitis (NEC) by ELISA and LFIA in a multi-center, cross-sectional study. Blood samples were collected from 47 infants with sepsis, 31 sepsis case controls, 52 gestational age (GA)-matched controls and 10 infants with culture-negative sepsis ("clinical sepsis"). We also collected samples from 17 infants with NEC, 7 NEC case controls and 15 GA controls. IAIP levels at presentation of acute events and over the next 72 hours were significantly reduced in infants with sepsis, NEC and culture negative sepsis when compared to controls. IAIP levels did not differ in patients with sepsis or culture negative sepsis. IAIP levels measured by ELISA and LFIA were highly correlated (R2 = 0.9326) and both showed reliable detection of neonatal sepsis, NEC and culture negative sepsis. IAIP levels were 80.0% sensitive and 92.3% specific using LFIA for the detection of neonatal sepsis. For detection of NEC, IAIP levels were 84.6% sensitive and 86.7% specific.