420 - Inter-alpha Inhibitor Proteins (IAIP) Levels Measured by Enzyme-linked Immunosorbent Assay (ELISA) & Lateral Flow Immunoassay (LFIA) Are Both Reliable Detections of Neonatal Sepsis

Inter-alpha Inhibitor Proteins (IAIP) are endogenous serine protease inhibitors

and a novel inflammatory biomarker. We have demonstrated that IAIP levels

decrease after immune activation in animal models and humans. Sepsis is a

systemic inflammatory response to overwhelming infection of the bloodstream.

Early diagnosis and treatment of sepsis are associated with improved outcomes.

Enzyme-linked immunosorbent assay (ELISA) is the standard laboratory procedure

to measure IAIP levels. We developed a quantitative lateral flow immunoassay

(LFIA) that allows rapid measurement of IAIP levels at point of care. We

hypothesized that infants with sepsis have significantly altered IAIP levels,

whether measured by ELISA or LFIA.

Objective:

To compare IAIP levels measured by a standard 6-hour ELISA and a rapid 15-

minute LFIA format in neonates with proven sepsis and controls.

Design/Methods:

A prospective, multi-center, cross-sectional study was conducted. Blood samples

were collected at acute event (clinical decision to take blood culture) and serially

thereafter at 24, 48, and 72 hours. We measured IAIP levels by ELISA (performed

in remote lab) and LFIA (can be performed bedside). We used a linear regression

to compare IAIP levels by ELISA and LFIA and a multivariate logistic regression to

assess associations with infant characteristics and outcomes. Finally we

determined the sensitivity and specificity of LFIA using the receiver operating

characteristic (ROC) curve.

Results:

Thirty-eight infants with sepsis, 22 case controls who had symptoms/signs of

sepsis without a positive blood culture, and 48 gestational age (GA)-matched

controls (Table) were recruited. GA controls had more maternal hypertension and

preeclampsia. The multivariate logistic regression showed IAIP levels at acute

event (ELISA and LFIA) and 72 hours after acute event (LFIA) were significantly

reduced in infants with sepsis (Figure 1) after controlling for GA (p-value < 0.05,

R² = 0.35). IAIP levels by ELISA and LFIA were highly correlated (R² = 0.94). The

area under curve (AUC) of the ROC analysis for LFIA to detect sepsis was 0.991

with the sensitivity of 96.3% and specificity of 94.6% at a cutoff value of 121

µg/ml (p < 0.001,  Figure 2).

Conclusion(s):

Significantly decreased IAIP levels in infants with sepsis suggest activation of the

neonatal systemic response to severe infection. IAIP levels measured by ELISA and

LFIA are both reliable for detection of sepsis. The simple point of care IAIP LFIA is

potentially useful for a rapid detection of sepsis.