Murat Sarikaya, Zeynal Dogan, Bilal Ergul, Levent Filik
Ankara Education and Research Hospital, Ankara, Turkey
Celiac disease (CD) is a small intestinal mucosal disease leading to malabsorbtion due to inflammatory reaction to gluten [1-4]. CD has a prevelance of approximately 1% of the population. But, it is estimated that up to 90% are undiagnosed due to subclinical presentations [5]. Also, diverse clinical manifestations can lead to delays in diagnosis [4]. Laboratory indices and biomarkers used in daily general medical practice are important in detecting new cases of CD, otherwise a delayed diagnosis can lead to development of important complications such as osteoporosis [6-9]. Neutrophil-to-lymphocyte ratio (NLR) was introduced as a useful index for diagnosis or prognosis of different diseases [7]. We hypothesized that NLR might change in patients with CD as an inflammatory disease. Blood count changes such as anemia, leukopenia are well-known but there is no data for NLR in CD [8,9]. In this regard, we prospectively checked the diagnostic role of the NLR in 76 patients with CD (M:26, F:50) at the time of diagnosis. Diagnosis of study patients was based on celiac antibodies (anti-gliadin, anti-endomysium and tissue transglutaminase), and duodenal biopsy [1,10]. Eighty-six patients with functional dyspepsia (M:33, F:53), all of whom had a normal complete blood cell count, C-reactive protein (CRP), and negative serology for anti-gliadin and anti-endomysium antibodies were recruited as control group. Statistical analyses were performed using SPSS version 17.0. Chi-square test was used for comparison of categorical variables. A P-value <0.05 was considered statistically significant. The Receiver Operating Characteristics (ROC) curve analysis was carried out to indicate the sensivity and specifity of NLR and its respective optimal cut-off value for predicting CD. Mean ages of groups were 38.5±12.11 years in CD patients and 36.5±12.2 years in controls (P>0.05). NLR was significantly higher in patients with CD (2.42±1.24) when compared to control group (1.92±0.58) (P<0.019). The success of NLR in diagnosing CD was statistically remarkable when tested with ROC analysis (Fig. 1). The cut-off value of NLR was 2.32. According to this cut-off value, sensitivity was 80% and specificity 41%.
Figure 1
The receiver-operating characteristic curve of neutrophil-to- lymphocyte ratio for predicting celiac disease
Neutrophils and lymphocytes are the cells that play a major role in inflammatory processes. Therefore, counts of neutrophils and lymphocytes temporarily change in inflammation. Cellular immunity obviously plays a major role in intestinal damage in CD [1,2,8]. The main pathogenesis of CD is believed to be related to a gluten-specific T-lymphocyte-mediated response resulting in an overexpression of interferon-γ in the epithelial compartment [1]. Inflammation is not confined to duodenum but also involves other gastrointestinal mucosa. Accordingly, surface lymphocytic infiltration of the stomach and colon can also be seen [9]. NLR change seems to be linked with this inflammation and cytokines. In conclusion, NLR might be used as a sensitive laboratory index in screening and diagnosis of CD.
References
1. Ciclitira PJ. Recent advances in coeliac disease. Clin Med 2003;3:166-169.
2. Rostami K, Kerckhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Antiendomysium and antigliadin antibodies in untreated celiacs: disappointing in clinical practice. Am J Gastroenterol 1999;94:888-894.
3. Dickey W, McMillan SA, Hughes DF. Sensitivity of serum tissue transglutaminase antibodies for endomysial antibody positive and negative coeliac disease. Scand J Gastroenterol 2001;36:511-514.
4. Rubio-Tapia A, Kyle RA, Kaplan EL, et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology 2009;137:88-93.
5. Lohi S, Mustalahti K, Kaukinen K, et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther 2007;26:1217-1225.
6. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG Clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013;108:656-676.
7. Motomura T, Shirabe K, Mano Y, et al. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol 2013;58:58-64.
8. Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood 2007;109:412-421.
9. See J, Murray JA. Gluten-free diet: the medical and nutrition management of celiac disease. Nutr Clin Pract 2006;21:1-15.
10. Marsh MN. Studies of intestinal lymphoid tissue. XI-The immunopathology of cell-mediated reactions in gluten sensitivity and other enteropathies. Scanning Microsc 1988;2:1663-1684.