C5a, A Complement Activation Product, Is a Useful Marker in Predicting the Severity of Necrotizing Enterocolitis

Abstract

Necrotizing enterocolitis (NEC) is the most common neonatal gastrointestinal emergency, predominantly affecting low-birth weight, premature infants. Early clinical signs of NEC are nonspecific and the laboratory findings are not fully reliable. Its severe morbidities and rapid progression require the application of new biomarkers for early diagnosis and intervention. The complement activation product, C5a (anaphylatoxin) has been reported to be a contributing factor leading to mesenteric ischemia/reperfusion injury which is a predisposing factor in the pathogenesis of NEC. Therefore, our aim was to evaluate the efficacy of serial C5a measurements in the diagnosis and follow-up of NEC. Preterm infants, whose gestational age and weight matched each other, were grouped as controls (n = 23) and NEC (n = 22). Serum levels of C5a, serum amyloid-A (SAA), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were measured on the third day of life for the control group and on the day of diagnosis (1 st day), 3 rd and 7 th days of the NEC group. C5a, SSA, CRP, and IL-6 levels were significantly higher in the NEC patients compared to the control group (P < 0.05) in the follow-up. Additionally, serum levels of C5a were found to be more accurate than the other parameters for the prediction of death and requirement for surgery at the time of diagnosis (P < 0.05). In conclusion, C5a may be useful as a new marker for both diagnosis and follow-up of infants with NEC in combination with clinical and radiographical findings.

Effects of polysaccharide intercellular adhesin (PIA) in an ex vivo model of whole blood killing and in prosthetic joint infection (PJI): A role for C5a

“…The constitutive levels of C5a in healthy volunteers are consistent with other studies (Kunkel et al, 1983;Stove et al, 1996;Tayman et al, 2011). However, addition of PIA to serum from healthy volunteers generated a threefold induction of C5a (from 20-60ng/ml) compared to control.…”

The Microbiome and Biomarkers for Necrotizing Enterocolitis: Are We Any Closer to Prediction?

“…The proinflammatory cytokine IL-8 h also has been correlated with disease severity, discriminating between medical (N=63) and surgical (N=50) NEC (AUC 0.82), and was found to be correlated significantly with 60-day mortality (odds ratio 1.38, CI 1.14–1.67) (51), similar to previous reports for both NEC and sepsis-like syndromes (36). Other recent markers of disease severity have included the “LIT” score based on liver (L)-FABP, I-FABP, and trefoil factor 3 differentiating surgical from non-surgical NEC at the onset of disease (52); the “Totalis” score based on both clinical and serum markers (53); and the complement activation product C5a (54). …”

Non-Invasive Serum Amyloid A (SAA) Measurement and Plasma Platelets for Accurate Prediction of Surgical Intervention in Severe Necrotizing Enterocolitis (NEC)

“…This group carries the highest mortality [3], and it is therefore essential to detect these severe cases at an early time point. In addition to clinical signs and symptoms, various plasma markers have been described to correlate with the severity of NEC, including serum amyloid A (SAA) [4], intestinal Fatty Acid Binding Protein (I-FABP) [5], [6], E-selectin [7], C5a [8] and IL-6 [9]. As venous puncture is a delicate and unfavorable procedure in neonates and a primary cause of anemia among preterm infants [10], [11], it is highly desirable to use non-invasive methods to discriminate neonates with severe NEC from those that can be treated conservatively.…”

“…Complement activation has been linked to the pathogenesis of NEC [19]; plasma levels of C5a are associated with perforation and death in patients with NEC [8]. The complement activation products C3a and C5a are important in all three complement pathways.…”