Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent protein mainly secreted by neutrophils. It can be detected in serum besides it can be secreted in stool or urine. It is strongly expressed in several infectious, inflammatory and malignant disorders including IBD. There is overexpression of NGAL in colon epithelium at time of inflammation. Thosvisk et al 2018 showed for the first time that NGAL is expressed in enteroendocrine cells in small intestine as well as in colon.
In this research, we studied serum NGAL in IBD patients either active or in remission and compared its level to healthy controls. Serum NGAL was significantly higher in IBD patient in activity versus those in remission with (mean ± SD) 37.04 ± 9.63 vs 20.65 ± 4.35 respectively (see table 2) .We have found that, NGAL showed highly significant correlation with clinical and endoscopic activity of IBD (Mayo score) r = 0.80, P < 0.000 (table 3). Serum NGAL can easily discriminate patients with active IBD from healthy controls with AUC with 95% C.I (0.94-1.0) = 1.00 ,at the cutoff 18.52, P < 0.0001, with sensitivity 100% and specificity 100%. While AUC of NGAL which can discriminate patients with active IBD and those in remission at the cutoff 26.95 was 0.97 with 95% CI (0.89–0.99), P < 0.0001, with sensitivity 93.3%, specificity 93.3% (Fig. 1A&1B).
Also it was found that AUC of NGAL discriminating patients who are in remission of IBD and healthy controls at the cutoff 14.91 was 0.95 ,with 95% CI (0.86–0.99), P < 0.0001, with sensitivity 93.33%, specificity 89.29% .
Johannes et al showed in his study in 2015 ,that there was a significant upregulation of serum NGAL in active IBD (median [IQR], 36.84 [21.17–73.74] ng/mL; P = 0.01) compared with healthy controls (24.22 [17.76–35.25] ng/mL). This elevated a high possibility of NGAL to be a marker of UC disease activity (AUC = 0.75, sensitivity 0.83, specificity 0.63; P = 0.0002). Many other studies were reporting the same results as, Oikonomou and his collegues who stated that serum NGAL can distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively. Budzynska etal in 2017 found almost same results. Thorsvisk et al 2017 and Abulganieva et al 2022 reported same finding not only for serum ,but also for fecal NGAL.
On the other hand, there was another study showed that serum NGAL concentrations did not differ between quiescent versus active stages. When a cut-off level of 129 ng/mL was used to distinguish IBD from healthy controls, of sensitivity 76.1% and specificity of 60.9% Yesil et al ,2013.
In our study it was found that most of the patients were below age of 40 about 70.5%. 58% were male sex, while 42% were female.54 patients (90%) were diagnosed as UC; 28 (51.9%) in remission MAYO 0–1, 26 patients (48.1%) in activity MAYO 2–3 score (table 1).
According to the extent of UC 7 patients were proctitis, 19 were proctosigmoiditis and 34 (56.7%) were pancolitis. 6 patients (10%) were diagnosed as CD; 2patients were in remission CDAI < 150 and the other 4 were in activity CDAI > 150. All of the patients were inflammatory CD. Three of the patients had history of appendectomy.
Furthermore, 53.3% of the patients were having extraintestinal manifestation either musculoskeletal or thromboembolic or skin or eye manifestation but all were controlled medically.All our patients were receiving medical conventional therapy 36.7% were taking 5 ASA (pentasa) and enemacort, while 63.3% were taking AZA and frequent use of steroids.
In relation to fecal calprotectin discriminating active versus remission of IBD at the cutoff 154, it was found that AUC was 0.93 CI (0.83–0.98), P < 0.0001, with sensitivity 90.0%, specificity 80.0% (Fig. 2). There was also highly significant correlation between fecal calprotectin and serum NGAL (r = 0.69, P < 0.0001). NGAL shows high significance of predictability of the activity of IBD (P < 0.0001) in comparison to fecal calprotectin. This goes in hand with Zollner et al 2021, who found that there was an excellent correlation between both [rS = 0.87, p < 0.001] and comparable sensitivity and specificity to predict clinical and endoscopic disease activity.
In addition a large multicentric cross-sectional study including 371 patients found that fecal calprotectin and NGAL levels are valuable addition for assessment of disease activity in asymptomatic UC patients.(Margo et al,2017)
Moreover our study (table 3) showed that CRP was positively correlated to NGAL, with mild positive correlation by r = 0.38 (P = 0.003).Yet, AUC of CRP that differs active IBD patients versus those in remission was only 0.56, with 95% CI (0.43–0.69), P = 0.42. While that of ESR was 0.55 CI (0.41–0.67), P = 0.54, with sensitivity 33.3%, specificity 83.3%. Thus, NGAL in comparison to other markers as CRP or ESR shows better statistical performance for activity of IBD.
This results can suggest the conclusion of De Bruyn et al., 2015 who showed that NGAL was better than CRP and can be used as a single marker in patients without elevated CRP levels or in combination with CRP to discriminate mucosal healing.
According to our knowledge, there was only one study done on 35 Egyptian IBD patients and showed the importance of serum NGAL as a marker in the assessment of patients regarding disease activity and response to treatment. (Nooh et al 2018)
In conclusion, we can recommend serum NGAL for assessment of IBD activity and may be potential prognostic marker and act as a highly significant predictor due to its lower cost in comparison to fecal calprotectin and being also very high sensitive and specific to active cases.