Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease
Por:
Moya-Alvarado, P, Lopez-Gomez, M, Martínez-Martinez, L, Park, HS, Leyva, TF, Martín, MC, Codes-Mendez, H, Lacruz, AC, Calleja, S, Magallares, B, Castellví, I, Barros-Membrilla, AJ, Bernárdez, J, Corominas, H
Publicada:
4 feb 2026
Resumen:
Background and Objectives: IgG4-related disease is a chronic fibro-inflammatory condition. Despite the development of classification and responder indexes, reliable biomarkers for disease activity and therapeutic monitoring remain limited. We evaluate the performance of a panel of biomarkers, including cytokine profiles, plasmablasts and conventional markers. Materials and Methods: We conducted a cross-sectional, single-center study, involving 35 patients diagnosed with IgG4-RD. Disease activity was evaluated using the IgG4-RD Responder Index (RI), Damage Index (DI) and clinical assessment. Laboratory evaluation included serum IgG4, total IgG, CRP, ESR, eosinophils, IgE, complement levels, and cytokine profiling via multiplex immunoassay. B cell subpopulations were analyzed by flow cytometry. Statistical analyses were performed using STATA/BE 17.0. Results: Patients with active disease (RI > 4 or clinical judgment) exhibited significantly higher levels of total IgG (p = 0.02), IgG4 (p = 0.01), and IL-5 (p = 0.03). PET-positive patients showed a Th1-skewed immune profile, with elevated IFN-gamma/IL-4 (p < 0.001), reduced IL-21/IFN-gamma (p = 0.03), and increased eosinophils (p = 0.03). Clinician-assessed active disease was associated with higher total IgG levels (p = 0.01). Treatment-specific effects were observed: prednisone was associated with lower IgG4 and C3 levels. Notably, plasmablasts did not consistently correlate with clinical or imaging activity scores, possibly reflecting treatment status or B cell dynamics. Conclusions: This study demonstrates that cytokine ratios, particularly those involving IL-5, IL-13, IL-21, and IFN-gamma, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-gamma-mediated pathway, the IgG4-RD RI demonstrated a stronger association with conventional humoral markers like serum IgG4 and total IgG. None of these biomarkers correlated with organ damage.
Filiaciones:
Moya-Alvarado, P:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Lopez-Gomez, M:
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Complex Hosp Univ Moises Broggi, Rheumatol Dept, St Joan Despi 08970, Spain
Martínez-Martinez, L:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Immunol Dept, IIB St Pau, Barcelona 08025, Spain
Park, HS:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Leyva, TF:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Immunol Dept, IIB St Pau, Barcelona 08025, Spain
Martín, MC:
Hosp Santa Creu & Sant Pau, Gastroenterol Dept, Barcelona 08025, Spain
Codes-Mendez, H:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Lacruz, AC:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Immunol Dept, IIB St Pau, Barcelona 08025, Spain
Calleja, S:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Immunol Dept, IIB St Pau, Barcelona 08025, Spain
Magallares, B:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Castellví, I:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Barros-Membrilla, AJ:
Hosp Santa Creu & Sant Pau, Cardiol Dept, Barcelona 08025, Spain
Bernárdez, J:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
Corominas, H:
Hosp Santa Creu & Sant Pau, Rheumatol Dept, Barcelona 08025, Spain
Univ Autonoma Barcelona UAB, Dept Med, Barcelona 08193, Spain
Inst Recerca St Pau IR ST PAU, Multiorgan Damage & Rheumatol Res Grp, Barcelona 08041, Spain
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