Abstract

Background:Retinol binding protein 4 (RBP4) is a plasma retinol transporter that transports retinol from liver to periphery. RBP4 has been studied as a biomarker in metabolic and neoplastic conditions, however its association with inflammation is not clear. Serum amyloid A (SAA), another retinol binding protein, has been known as a sensitive biomarker of inflammation in familial Mediterranean fever (FMF) and other autoinflammatory disorders. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and SAA are commonly used as acute phase reactants, but they are not successful in differentiating non-infectious inflammatory conditions from infections.Objectives:We aimed to evaluate the potential of serum RBP4 as a biomarker of acute phase response and to determine its performance in differentiation of inflammation of patients with FMF and AA amyloidosis from infections.Methods:A total of 169 participants in 5 groups, consisting of FMF (n = 60), FMF with AA amyloidosis (n = 58), non-FMF AA amyloidosis (n = 23), infections (n = 10, 3 pneumonia, 3 sepsis, 1 pyelonephritis, 1 fungal infection, 1 cellulitis, 1 disseminated zoster), and healthy controls (HC) (n = 18), were included and evaluated cross sectionally. Hemogram and serum CRP, ESR, SAA, ferritin, creatinine, AST, ALT, albumin levels were recorded from the patient charts. FMF and FMF + amyloidosis patients were evaluated during attack-free period. Serum RBP4 levels were investigated by ELISA (Elabscience, USA). Mean values and relative changes compared to healthy controls were evaluated for SAA, CRP, RBP4 levels in all groups.Results:Serum RBP4 level was found to be higher in FMF group compared to the patients with infection (p = 0.002) and HC (p <0.001) as well as in patients with amyloidosis. Compared to HC, 47%, 28% and 27% increase was observed in mean RBP4 levels in FMF, FMF + amyloidosis and non-FMF amyloidosis patients, despite no significant change in patients with infections. However, CRP and SAA elevations were much more prominent in patients with infections (58 and 134 times, respectively) compared to the patients with FMF (13 and 35 times, respectively), FMF + amyloidosis and non-FMF amyloidosis (Table 1). There was no significant difference in RBP4 levels between FMF, FMF-amyloidosis and non-FMF amyloidosis groups. CRP, ESR, ferritin and SAA levels were higher in the infection group compared to HCs.Table 1.Demographic features and laboratory findings of the participantsVariablesFMF(n=60)FMF- Amyloidosis(n=58)Non-FMF-AA Amyloidosis(n=23)Infection(n=10)Healthy control(n=18)Female/Male46/1433/258/153/78/10Age (SD)*38±13(18-74)43±11(21-69)53±1365±1533±9Creatinine (mg/dL)*0,8±0,21,7±1,72,0±1,61,7±1,00,7±0,2Albumin(mg/dL)*4,7±0,44,3±0,63,3±0,93,0±0,94,8±0,2Ferritin (ng/mL)*70±94245±315139±168554±3883±72RBP4 (ng/mL)*772±183671±214666±256512±204524±117RBP4 (median)770(434-1142)653(227-1259)645(331-1214)487(226-876)498(566-738)CRP (mg/L)*16±47,112,8±32,825,7±36,469±36,81,2±1,2SAA (mg/dL)*10,3±31,45,0±13,97,1±14,140,2±18,50,3±0,1ESR*15±1319±1641±2945±427±5Relative RBP4 increase1,47±0,351,28±0,411,27±0,490,98±0,39Relative CRP increase13,4±39,210,6±27,321,4±30,357,7±30,6Relative SAA increase34,5±104,816,0±45,723,7±47,1133,9±61,7*mean, RBP4 (Retinol Binding Protein 4), C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Serum Amyloid A (SAA).Conclusion:This preliminary study showed that RBP4 levels may be increased about 1.5 times in FMF and to lesser extent in AA amyloidosis patients despite no significant change during acute phase response of different infections. Patients with infections show strong CRP and SAA response, and the differential response of RBP4 in FMF patients warrants further analysis in larger group of patients with different clinical characteristics.Disclosure of Interests:None declared

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