Immunological Biomarkers to Assess Activity and Treatment Response in IgG4-Related Disease
Moya, Patricia (Universitat Autònoma de Barcelona. Departament de Medicina)
Lopez-Gomez, Marta (Hospital de Sant Joan Despí Moisès Broggi)
Martinez-Martinez, Laura (Universitat Autònoma de Barcelona. Departament de Biologia Cel.lular, de Fisiologia i d'Immunologia)
Park, Hye S. (Universitat Autònoma de Barcelona. Departament de Medicina)
Franco Leyva, Teresa (Universitat Autònoma de Barcelona. Departament de Biologia Cel.lular, de Fisiologia i d'Immunologia)
Concepción, Mar (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Codes Méndez, Helena (Universitat Autònoma de Barcelona. Departament de Medicina)
Calvet Lacruz, Anna (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Calleja, Sara (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Magallares López, Berta Paula (Institut de Recerca Sant Pau)
Castellvi, Ivan (Universitat Autònoma de Barcelona. Departament de Medicina)
Barros-Membrilla, Antonio J. (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Bernárdez, Julia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Corominas, Hèctor (Universitat Autònoma de Barcelona. Departament de Medicina)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2026
Resum:	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-γ/IL-4 (p < 0. 001), reduced IL-21/IFN-γ (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-γ, offer complementary information to traditional serological markers for IgG4-RD activity. While PET/CT-defined activity was best reflected by biomarkers of an IFN-γ-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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	IgG4-related disease ; Disease activity ; Responder Index ; IgG4 ; Serology ; Biomarkers ; Cytokines ; Immune profiling ; PET/CT ; Treatment
Publicat a:	Medicina, Vol. 62, Num. 2 (February 2026) , art. 323, ISSN 1648-9144

DOI: 10.3390/medicina62020323

16 p, 498.7 KB

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