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TOPLINE:

Chemokine (C-C motif) ligand 19 (CCL19) emerged as a biomarker for monitoring disease activity in immunoglobulin (Ig)G4-related disease. Among 12 inflammation-associated proteins with elevated levels in IgG4-related disease, CCL19, CCL2, and CCL13 most effectively distinguished patients with IgG4-related disease from healthy donors. CCL19 and IgG4 levels rose during active disease, declined with treatment-induced remission, and increased at relapse.

METHODOLOGY:

• Researchers screened 92 inflammation-associated proteins using a proximity extension assay in 67 patients with IgG4-related disease as well as 49 healthy donors and 21 patients with sarcoidosis in the US to identify novel biomarkers of disease activity.
• All patients with IgG4-related disease met the 2019 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria with a score > 20. Among patients with IgG4-related disease, 31 were treatment-naive with active disease, 28 had relapsing active disease, and 16 were in posttreatment remission (eight with paired samples collected during active disease and remission).
• Validation was performed using quantitative enzyme-linked immunosorbent assay (ELISA) in 80 patients with IgG4-related disease (43 treatment-naive and 37 with relapsing disease), including 28 patients with paired longitudinal samples, and 80 age-, sex-, and race-matched healthy donors.
• Plasma levels of CCL19 and IgG4 were measured using ELISA, and plasma samples were compared among patients with active IgG4-related disease, patients with IgG4-related disease in remission, healthy donors, and patients with sarcoidosis. Flow cytometry was used to examine activated B- and T-cell populations in a subset of patients and correlate them with serum CCL19 levels.

TAKEAWAY:

• Comparative analysis identified 12 inflammation-associated proteins that distinguished patients with IgG4-related disease from healthy donors.
• CCL19, CCL2, and CCL13 exhibited the highest discriminative accuracy, with area under the curve values of 0.781, 0.766, and 0.752, respectively, and levels of all three proteins were significantly elevated in patients with IgG4-related disease vs both healthy donors and patients with sarcoidosis (P ≤ .01).
• Among the top biomarkers, only CCL19 levels demonstrated a significant reduction following treatment-induced remission relative to active IgG4-related disease (P ≤ .001). CCL19 levels correlated with levels of IgG, IgG1, IgG4, and IgE, as well as the absolute eosinophil count and the eosinophil-to-lymphocyte ratio.
• In longitudinal samples from nine patients with initial disease activity, posttreatment remission, and subsequent relapse, CCL19 and IgG4 levels performed similarly, with both levels increasing again at the time of disease relapse in some, but not all, patients.

IN PRACTICE:

“[T]hese analyses demonstrate that combining CCL19 and IgG4 improved performance compared with either biomarker alone in discriminating active disease from remission. We provide novel data supporting the use of both CCL19 and IgG4 for monitoring longitudinal disease activity in IgG4-RD,” the authors of the study wrote.

SOURCE:

The study was led by Federica Bonaso, Division of Rheumatology, Immunology, and Inflammation, Massachusetts General Brigham, Boston. It was published online on May 13, 2026, in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although the cohort size was substantial for a rare disease, it restricted a more detailed analysis of clinical phenotypes or specific organ manifestations where CCL19 may be particularly relevant. The study was not designed to identify biomarkers with diagnostic potential, and there were no additional disease controls beyond sarcoidosis included.

DISCLOSURES:

The research was supported by the National Institutes of Health (NIH), including grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the NIH Autoimmunity Centers of Excellence to authors. Two authors disclosed consulting or advisory roles and/or board membership with various companies; a third author disclosed being employed by Amgen.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.