Serum and Urine Biomarker Leucine-Rich Alpha-2 Glycoprotein 1 Differentiates Pediatric Acute Complicated and Uncomplicated Appendicitis

Abstract

Purpose: This prospective, single-center cohort study analyzes the potential of inflammatory protein mediator leucine-rich alpha-2 glycoprotein 1 (LRG1) for the early and accurate diagnosis of acute appendicitis (AA), and differentiation of acute complicated (AcA) from uncomplicated appendicitis (AuA). Methods: Participants were divided into the AcA, AuA, and control groups, and their serum (s-LRG1) and urine LRG1 (u-LRG1) levels were assayed preoperatively on the second and fifth postoperative days. Results: 153 patients participated, 97 had AA. Preoperative u-LRG1 with a cut-off value of 0.18 μg/mL generated an area under the receiver operated characteristic (AUC) curve of 0.70 (95% CI 0.62–0.79) for AA versus control (p < 0.001), while the results for AcA versus AuA were not significant (AUC 0.60, 95% CI 0.49–0.71, p = 0.089). The s-LRG1 levels of AA versus the control with a cut-off value of 51.69 μg/mL generated an AUC of 0.94 (95% CI 0.91–0.99, p < 0.001). The cut-off value of s-LRG1 was 84.06 μg/mL for diagnosis of AcA from AuA, and therefore, significant (AUC 0.69, 95% CI 0.59–0.80, p = 0.001). Conclusions: LRG1 exhibited excellent diagnostic performance as an inexpensive, non-invasive, rapid, and accurate biomarker able to reflect the pathogenesis of AA. LRG1 has the potential to replace advanced imaging to diagnose clinically ambiguous AA cases.

Diagnostic Utility of Serum Leucine-Rich α-2-Glycoprotein 1 for Acute Appendicitis in Children

“…Furthermore, due to the restrictions on the number of participants admitted to this study, the control group consisted of the patients with different surgical conditions, such as fractures, testicular torsion, etc. and the patients with non-specific abdominal pain were not included [ 43 ]. On the contrary, to differentiate acute appendicitis from non-specific abdominal pain, in our control group, we included children who had non-specific abdominal pain but in whom the diagnosis of acute appendicitis had been ruled out by diagnostic procedures.…”

“…However, extensive use of diagnostic imaging has been severely restricted by a variety of factors, including immediate accessibility, cost, exposure of children to radiation from CT scans and the national guidelines [ 35 , 36 ]. Notable studies are focused on utilizing new biomarkers of inflammation that are accessible, easily detected and affordable in order to accurately diagnose acute appendicitis [ 1 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…To date, several biomarkers, such as fibrinogen, red cell distribution width, mean platelet volume, interleukins, CRP, procalcitonin, 5-hydroxyindoleacetic acid, hyponatremia or hyperbilirubinemia, have been investigated for acute appendicitis with varying diagnostic accuracy in published studies [ 1 , 21 , 22 , 46 ]. A novel protein biomarker known as leucine-rich alpha-2-glycoprotein 1 (LRG1) has recently been found in the diseased appendices and has been elevated in the serum, urine and saliva of patients with acute appendicitis [ 42 , 43 , 44 , 45 , 46 , 47 ]. Even though its exact physiological function is relatively unclear, recent studies have confirmed that LRG1 is involved in cell adhesion and signal transduction [ 47 , 48 ].…”

Case Series of Variable Acute Appendicitis in Children with SARS-CoV-2 Infection

“…Acute uncomplicated appendicitis may be treated solely with antibiotics; however, when it progresses to acute complicated appendicitis, surgical treatment is necessary. Delayed diagnosis and treatment of acute appendicitis may lead to complications such as peritonitis, intra-abdominal abscess, sepsis, ileus, or even patient death [ 16 ]. The COVID-19 pandemic gave rise to many fears about hospitalisation and prolonged stays in the ED, considering potential cross-infection and delays in treatment due to disease control measures and other logistical restrictions.…”

Serum leucine-rich alpha-2 glycoprotein levels in rheumatoid arthritis and spondyloarthritis: A promising biomarker

“…Increased pro-inflammatory cytokines, especially IL-6, has been shown to indirectly increase LRG. [19][20][21] Studies assessing LRG levels in the synovial fluid of RA and SpA patients have previously been conducted, with varying results being obtained. Several studies examining LRG levels in synovial fluid, including one by Birkelund et al, reported that synovial fluid proteomics analysis from SpA and RA patients showed striking differences in the amount of innate immune system proteins, especially those from neutrophil granulocytes, including LRG.…”