PO:24:058 | Serum ferritin as a biomarker in idiopathic inflammatory myopathies with interstitial lung disease: baseline levels and longitudinal trends

Silvia Grazzini¹, Edoardo Conticini¹, Marco Fornaro², Chiara Rizzo³, Federica Camarda³, Paolo Cameli⁴, Miriana D'Alessandro⁴, Lidia La Barbera³, Stefano Stano², Maria Rosa Pellico⁵, Latika Gupta⁶, Florenzo Iannone², Giuliana Guggino³, Elena Bargagli⁴, Nicoletta Del Papa⁵, Luca Cantarini¹, Bruno Frediani¹. | ¹Reumatologia, Dipartimento di Scienze Mediche, Chirugiche e Neuroscienze, Università di Siena, Siena, Italy; ²Reumatologia, Dipartimento di Emergenza e Trapianto d'Organo, Università di Bari, Bari, Italy; ³Reumatologia, Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy; ⁴Pneumologia, Dipartimento di Scienze Mediche, Chirugiche e Neuroscienze, Università di Siena, Siena, Italy; ⁵Reumatologia Clinica e Scienze Mediche, ASST Gaetano Pini CTO, Milano, Italy; ⁶University of Manchester, Manchester, United Kingdom.

Background. Serum ferritin has been proposed as a biomarker of interstitial lung disease (ILD) in anti-MDA5 dermatomyositis (DM), but data on its role in other idiopathic inflammatory myopathies (IIM) with or without ILD are limited. This multicenter retrospective study aimed to evaluate serum ferritin as a specific and sensitive biomarker for IIM-ILD and to assess its correlation with clinical and immunological features, including a subanalysis on longitudinal ferritin changes in anti-MDA5 DM and antisynthetase syndrome (ASS) patients.

Materials and Methods. We retrospectively included 139 adult patients with a definite diagnosis of IIM according to 2017 ACR/EULAR criteria, followed at referral centers in Siena, Palermo, Bari (Italy) and Lucknow (India). All had available baseline data on serum ferritin, muscle enzymes, inflammatory markers, lung function and myositis-specific antibodies: patients were grouped by ILD status and clinical phenotype. In a subgroup of 23 ILD patients (11 anti-MDA5 DM, 12 anti-Jo1 ASS), longitudinal data were analysed.

Results. We enrolled 139 IIM patients (mean age 44.3±17.75 years), including 70 DM and 50 ASS , with 69 affected by ILD. Baseline ferritin was significantly higher in DM-MDA5 compared to DM-non-MDA5 (p=0.0073) and ASS (p=0.0006), and also differed between patients with and without ILD (p=0.0013) (figure 1). A ferritin cut-off of 303.5 ng/mL effectively excluded MDA5-DM at initial assessment, independently of CPK and CRP, suggesting ferritin’s specificity beyond systemic inflammation. A longitudinal subanalysis of 23 ILD patients (11 anti-MDA5 DM, 12 anti-Jo1 ASS) evaluated ferritin, disease activity, CRP, ESR, at baseline and up to 18 months. Despite ASS patients showing more extensive organ involvement (> 4 domains in 66%), baseline ferritin was higher in DM (median 312 vs 82 ng/mL, p=0.007), whereas CPK was elevated in ASS (median 336 vs 101 U/L, p=0.05). Over follow-up, DM patients demonstrated a progressive ferritin decline at 12 and 18 months (p=0.025 and p=0.017, figure 2), closely mirroring improvements in PhGA (p<0.05). ASS patients showed no significant ferritin changes (figure 2) despite clinical improvement. CRP and ESR fluctuated without consistent trends, limiting their value in monitoring disease activity.

Conclusions. These data confirm serum ferritin’s utility as a diagnostic and dynamic biomarker specifically for anti-MDA5 DM-ILD. Its progressive decline may support its use in real-life clinical decisions, while the absence of a similar pattern in ASS highlights pathophysiological heterogeneity and the need for tailored approaches in IIM subtypes. Limitations include the retrospective design, small sample size in the longitudinal analysis, treatment variability, lack of standardized follow-up. Nonetheless, this study provides evidence supporting ferritin’s dual role in identifying and monitoring anti-MDA5 DM-ILD. Prospective studies in larger, diverse cohorts are warranted to validate these findings and potentially integrate ferritin into future disease activity scores.