Abstract

Crohn's disease (CD) is an inflammatory bowel disease (IBD) that can affect the entire gastrointestinal tract and can have a major impact on the patient's quality of life. Asymptomatic patients, or those with mild symptoms, experience the active disease with subclinical manifestation. A systematic review (SR) was performed to look for evidence for the role of chemokines and adipokines as markers for CD activity. This SR was conducted by searching published studies in international and regional databases up to July 2020. CD patients were adults with the disease in activity or remission. All adipokines and chemokines were considered for the analysis and the Rayyan QCRI system was used. The selection of articles published in the Rayyan system was carried out by two reviewers, autonomously and independently, and a third reviewer was responsible for analysing and deciding on the inclusion or exclusion of the article, especially in relation to those who presented a contradictory and conflicting decision. The search for articles was carried out in the databases PUBMED, PUBMED PM C, BVSBIREME, SCOPUS, WEB OF SCIENCE, EMBASE, COCHRANE, EBSCOHOST, PROQUEST and ENDNOTE WEB. The keywords "Crohn's disease", "chemokines", "adipokines", "biomarkers" and "inflammation" were chosen after reading material related to the researched topic. To expand and guide the search, an association of the descriptors was carried out by means of Boolean operators "OR" and "AND". The Boolean operators "OR" and "AND" were used to add or restrict the search, as follows: "Crohn Disease AND Biomarkers AND (Chemokines OR Adipokines) AND Inflammation". Only studies with human samples were considered. In total, 20 studies were included from 344 which were found in the databases. Six addressed chemokines and eight adipokines as potential biomarkers of CD activity. CXCL8 was the most studied chemokine (8 studies) and the results were controversial, with 62.5% showing a significant association with CD activity. CXCL10 was investigated by 4 studies and 50% identified it as a potential biomarker. CCL2, CCL11, CCL26 and CXCL1 were examined by 2 articles each. CXCL8 (P=0.002/P=0.001) and CXCL1 (P < 0.001) presented the lowest P value, which qualifies them as potential markers of disease activity. All the adipokines were tested in peripheral blood but 44.4% were also tested in intestinal mucosa, while the percentage in the chemokines' studies was 76.9% in peripheral blood, 46.1% in intestinal mucosa and 7.6% in urine sample respectively. Despite the limitations and the small number of studies found in the literature that followed the criteria of this SR, some chemokines (CCL2, CCL20, CXCL1, CXCL3, CXCL8, CXCL10 and CXCL1) and adipokines (leptin, IL-6 and TNF-α) have unveiled promising results that may enable us to distinguish active versus in remission forms of CD based on objective criteria of inflammation such as endoscopic, histologic or radiological criteria. The development of disease activity biomarkers for CD is becoming relevant for clinical practice, and chemokines and adipokines have the potential to signalize CD activity. However, validation in larger cohorts of patients, preferable multicenter studies are still needed.

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