Serum Ferritin in Inflammatory Bowel Disease: Determinants, Variations, and the Association With Inflammation

Background and aim: Serum ferritin is the first-line marker of iron stores, but it is also an acute-phase reactant.In inflammatory bowel disease (IBD), where iron deficiency and inflammation frequently coexist, the interpretation of ferritin is therefore challenging.The primary objective of this study was to describe the distribution and the clinical and biological determinants of serum ferritin in patients with IBD, and to characterize the association between ferritin and inflammation assessed by C-reactive protein (CRP).Secondary objectives were to evaluate ferritin variations according to CRP both across patients and within patients over time, and to compare the prevalence of suspected iron deficiency according to different guideline-based classification criteria.The analysis of CRP thresholds above which the inflammatory association with ferritin becomes most prominent was an exploratory objective.Methods: We conducted a retrospective study at the Laboratory of Biochemistry of Mohammed VI University Hospital, Oujda, Morocco, including 150 laboratory panels with simultaneous ferritin and CRP from 119 patients with IBD.Ferritin was measured by chemiluminescent microparticle immunoassay and CRP by immunoturbidimetry.Ferritin levels were compared across clinical and biological subgroups and CRP categories; correlations were stratified by CRP levels, and determinants of log-transformed ferritin were assessed using multivariable linear regression.A patient-level sensitivity analysis restricted to one panel per patient confirmed the primary associations.Results: Median ferritin was 37.1 ng/mL (interquartile range: 13.8-94.3).Ferritin was lower in women (22.5 vs. 52.3ng/mL; p=0.006) and in anemic patients (19.9 vs. 42.4ng/mL; p=0.006), and higher in endoscopically active disease (44.7 vs. 25.7 ng/mL; p=0.049).Ferritin concentrations increased with CRP, from 28.4 ng/mL with CRP ≤5 mg/L to 110.9 ng/mL with CRP >50 mg/L (p=0.001).Ferritin concentration was ≥100 ng/mL in 50.0% of panels, compared with CRP >20 mg/L in 18.9% of panels (p<0.001).When CRP was ≤5 mg/L, ferritin was unrelated to CRP (Spearman's rank correlation coefficient {ρ}=0.03)and correlated with hemoglobin (ρ=0.49;p<0.001); when CRP was >5 mg/L, ferritin correlated with CRP (ρ=0.39;p=0.001) and the relationship with hemoglobin was attenuated (ρ=0.09;p=0.48).In multivariable analysis, CRP, hemoglobin, and endoscopic activity were independent determinants of ferritin.Consequently, 32.5% of inflamed panels had ferritin 30-99 ng/mL, a range that may conceal iron deficiency according to European Crohn's and Colitis Organisation (ECCO) criteria.Conclusions: In IBD, higher CRP concentrations are associated with higher ferritin values and an attenuation of the relationship between ferritin and iron-related erythropoiesis, particularly when CRP exceeds 10 mg/L (an exploratory finding requiring prospective validation).Ferritin should always be interpreted together with CRP and complemented by markers less influenced by inflammation when CRP is elevated.