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Abstract Background The aim of this study was to identify fibrosis-related serological surrogate outcome measures in patients with immunoglobulin G4-related disease (IgG4-RD). Methods This was a clinical observational study of 72 patients with untreated IgG4-RD from four institutions in Japan. The serum concentrations of growth differentiation factor 15 (GDF-15), CCL2, hyaluronic acid (HA), amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assays. The enhanced liver fibrosis (ELF) score was calculated from the TIMP-1, PIIINP, and HA values. We evaluated associations between the values of these biomarkers and laboratory data, the IgG4-RD responder index (IgG4-RD RI) score, and organ involvements. Results Compared with the 44 healthy controls, the patients with IgG4-RD showed significantly elevated serum concentrations of GDF-15, MCP-1, HA, PIIINP, and TIMP-1 and ELF scores. The patients’ serum concentrations of GDF-15, CCL2, HA, and TIMP-1 (but not PIIINP) were positively correlated with each other. Among them, serum GDF-15 most efficiently distinguished patients with IgG4-RD from healthy controls. Serum GDF-15 was not associated with the IgG4-RD RI score or the number of organ involvements but was independently associated with the presence of retroperitoneal fibrosis and with parotid gland involvement. Conclusions We observed increased serological surrogate outcome measures of fibrosis in IgG4-RD. GDF-15 may precisely reflect the fibrotic degree in patients with IgG4-RD.

La enfermedad relacionada con IgG4 (ER-IgG4) es una enfermedad sistémica reconocida. Se describió tras observarse que pacientes diagnosticados de pancreatitis autoinmune mostraban signos de enfermedad extrapancreática. La clínica de estos pacientes es subaguda y se manifiesta por aparición de lesiones seudotumorales, o tumores inflamatorios o fibrosos. En ocasiones, puede ser grave, como en el caso de pacientes con colangitis o vasculitis de gran vaso. Los criterios diagnósticos incluyen, entre otros, elevación sérica del valor de IgG4 o parámetros histológicos. La 18F-FDG-PET/TC es útil en el diagnóstico inicial, guía de biopsia, así como en la valoración de respuesta a la terapia. Habitualmente, responde al tratamiento con corticoides. IgG4-related disease (ER-IgG4) is a recognised systemic disease. It was described after patients diagnosed with autoimmune pancreatitis showed signs of extra-pancreatic disease. The clinical manifestation of these patients is subacute and is manifested by the appearance of pseudotumoral lesions, or inflammatory or fibrous tumours. Sometimes it can be serious as in the case of patients with cholangitis or large vessel vasculitis. Diagnostic criteria include, among others, serum IgG4 elevation and/or histological parameters. The 18F-FDG-PET/CT is useful in the initial diagnosis, biopsy guidance as well as in the assessment of response to therapy. It usually responds to steroid therapy. [ABSTRACT FROM AUTHOR]

Objectives: IgG4-related disease (IgG4-RD) is a chronic fibro-inflammatory disorder affecting virtually any organ. Type 1 autoimmune (type 1 AIP) is its pancreatic manifestation. To date, steroids are considered the first-line pancreatitis treatment. The CD20-binding antibody rituximab (RTX) appears a promising steroid-sparing therapy, although long-term data are lacking. We aimed to bridge this gap with a cohort of IgG4-RD patients treated with RTX and to assess the potential value of the Responder Index (RI) as a discriminatory score for disease activity. Methods: We retrospectively evaluated 46 patients from a tertiary referral centre who were diagnosed with IgG4-RD and/or type 1 AIP according to the International Consensus Diagnostic Criteria or Unifying-AIP criteria between June 2006 and August 2019. Results: Patients resembled previous cohorts in terms of characteristics, diagnosis, and therapeutic response. Thirteen of the 46 patients with IgG4-RD/type 1 AIP were treated with RTX pulse therapy due to relapse, adverse reactions to steroids, or high-risk constellations predicting a severe course of disease with multi-organ involvement. Median follow-up after diagnosis was 52 months for all subjects, and 71 months in IgG4-RD patients treated with RTX. While patients in the RTX group showed no significant response to an initial steroid pulse, clinical activity as measured by the RI significantly decreased in the short-term after RTX induction. Within 16 months, 61% of patients relapsed in the RTX group but responded well to re-induction. Clinical and laboratory parameters improved equally in response to RTX. Conclusion: RTX therapy in patients with IgG4-RD is an effective and safe treatment to induce treatment response and possible long-term remission. Repeated RTX administration after 6–9 months may be of value in reducing the risk of relapse. The RI appears to be a reasonable index to assess disease activity and to identify patients with IgG4-related disease who may benefit from B-cell-depleting therapy. [ABSTRACT FROM AUTHOR]

IgG4-related disease (ER-IgG4) is a recognised systemic disease. It was described after patients diagnosed with autoimmune pancreatitis showed signs of extra-pancreatic disease. The clinical manifestation of these patients is subacute and is manifested by the appearance of pseudotumoral lesions, or inflammatory or fibrous tumours. Sometimes it can be serious as in the case of patients with cholangitis or large vessel vasculitis. Diagnostic criteria include, among others, serum IgG4 elevation and/or histological parameters. The 18F-FDG-PET/CT is useful in the initial diagnosis, biopsy guidance as well as in the assessment of response to therapy. It usually responds to steroid therapy., (Copyright © 2021 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The aim of this study was to identify fibrosis-related serological surrogate outcome measures in patients with immunoglobulin G4-related disease (IgG4-RD)., Methods: This was a clinical observational study of 72 patients with untreated IgG4-RD from four institutions in Japan. The serum concentrations of growth differentiation factor 15 (GDF-15), CCL2, hyaluronic acid (HA), amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by enzyme-linked immunosorbent assays. The enhanced liver fibrosis (ELF) score was calculated from the TIMP-1, PIIINP, and HA values. We evaluated associations between the values of these biomarkers and laboratory data, the IgG4-RD responder index (IgG4-RD RI) score, and organ involvements., Results: Compared with the 44 healthy controls, the patients with IgG4-RD showed significantly elevated serum concentrations of GDF-15, MCP-1, HA, PIIINP, and TIMP-1 and ELF scores. The patients' serum concentrations of GDF-15, CCL2, HA, and TIMP-1 (but not PIIINP) were positively correlated with each other. Among them, serum GDF-15 most efficiently distinguished patients with IgG4-RD from healthy controls. Serum GDF-15 was not associated with the IgG4-RD RI score or the number of organ involvements but was independently associated with the presence of retroperitoneal fibrosis and with parotid gland involvement., Conclusions: We observed increased serological surrogate outcome measures of fibrosis in IgG4-RD. GDF-15 may precisely reflect the fibrotic degree in patients with IgG4-RD.