Can Calprotectin Show Subclinical Inflammation in Familial Mediterranean Fever Patients?

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease that has self-limiting inflammatory attacks during polyserositis. Hepcidin is a protein, and interleukin-6 stimulation increases hepcidin levels. Calprotectin (CLP) is a recently defined cytokine released from monocytes and neutrophils in response to tissue trauma and inflammation. There are studies in the literature showing that it can be used as a biomarker in rheumatic diseases such as ankylosing spondylitis and rheumatoid arthritis. Here, we compared the levels of hepcidin and CLP in healthy individuals and FMF patients during an attack-free period and show its relation to genetic mutations. METHODS: This is a cross-sectional study. Between July 2017 and December 2017, 60 patients diagnosed with FMF an admitted to the Cumhuriyet University Faculty of Medicine Department of Internal Medicine Rheumatology as well as 60 healthy volunteers without any rheumatic, systemic, or metabolic diseases were enrolled in this study. Blood was collected from a peripheral vein to measure serum CLP and hepcidin levels. Blood tests were examined by ELISA; the study protocol was approved by the local ethics committee. RESULTS: Median serum hepcidin level was 468.1 (210.3-807.8) pg/mL in FMF group and 890.0 (495.0-1,716.9) pg/mL in the healthy control (HC) group. There was a statistically significant difference between the two groups (P < 0.001). The median serum levels of CLP in the FMF group were measured as 1,331.4 (969.3-1,584.6 pg/mL and 73.8(45.0-147.9) pg/mL in the HC group. There was a statistically significant difference between the two groups (P < 0.001). Receiver operating characteristic analysis showed that the sensitivity was 66.7% and the specificity was 71.7% at serum hepcidin < 581.25 pg/mL (P < 0.05); the sensitivity was 96.7% and specificity was 100% at CLP > 238 pg/mL (P < 0.05). There was no significant difference between serum hepcidin and CLP levels in FMF patients with M694V homozygous and M694V heterozygous (P > 0.05). There was no significant difference in serum hepcidin levels between FMF patients with and without arthritis, proteinuria, and amyloidosis (P < 0.05). There was no significant correlation between laboratory findings, gender, age, and serum CLP and hepcidin levels (P > 0.05, r < 0.25). CONCLUSION: Serum CLP levels in FMF patients during an attack-free period are significantly higher than in the HC groups. Serum hepcidin levels in FMF patients are significantly lower than in the HC group. Low levels of hepcidin may be explained by including FMF patients during an attack-free period in the study. CLP may be an important biomarker in FMF. A better understanding of the role of these biomarkers in the diagnosis of FMF is needed to evaluate the results in a more comprehensive way.

High prolidase levels in patients with Familial Mediterranean Fever (FMF).

INTRODUCTION: Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group. METHODS: Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study. RESULTS: Median serum prolidase levels were 72.1 (25.1-114.9) ng/ml in FMF group and 30.7 (21.3-86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1α in the FMF group was 482.0 (292.0-3967.0) pg/mL and 632.0 (362.0-927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05). CONCLUSION: Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.