Double-Negative B Cell Expansion Defines a Relapse-Prone Immunophenotype in Newly Diagnosed Giant Cell Arteritis

Nieto-Carvalhal, B.; Monjo-Henry, I.; Campos-Fabre, C.; Garcia-Carazo, S.; Bohorquez, C.; Villalba, A.; Peiteado, D.; de Miguel, E.; Miranda-Carus, M.-E.

doi:10.64898/2026.09.25.754436

bioRxiv · 10.64898/2026.09.25.754436

Double-Negative B Cell Expansion Defines a Relapse-Prone Immunophenotype in Newly Diagnosed Giant Cell Arteritis

Nieto-Carvalhal, B.·Monjo-Henry, I.·Campos-Fabre, C.·Garcia-Carazo, S.·Bohorquez, C.·Villalba, A.·Peiteado, D.·de Miguel, E.·Miranda-Carus, M.-E.

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Abstract

Background: Giant cell arteritis (GCA), traditionally considered T cell-driven, exhibits vascular B/plasma-cell infiltrates and altered circulating B-cell homeostasis, suggesting a pathogenic role for B cells. Relapse is common in newly diagnosed GCA (nGCA), yet predictive biomarkers remain elusive. Objective: To characterize circulating B-cell subpopulations in nGCA and assess their association with 12-month relapse. Methods: Baseline multiparametric flow cytometry was performed on peripheral blood samples from consecutive patients with nGCA and sex/age-matched healthy controls (HC). Patients received standard treatment per 2018 EULAR recommendations and were followed longitudinally. Results: 102 patients with nGCA and 102 matched HC were included. One-year outcome data were available for 55 patients, of whom 34 relapsed and 21 remained relapse-free. Baseline B-cell homeostasis differed by disease course. Non-relapsers showed reduced total CD19+ B-cell counts and contraction of most B-cell subsets, while CD27-IgD-double-negative (DN) B-cell counts remained comparable to HC. Conversely, relapsers maintained total B-cell numbers above HC despite reduced memory compartments, driven by expanded naive and DN B cells, alongside preserved plasmablast and transitional B-cell counts. At 6 months, total B-cell counts increased only in non-relapsers. DN B cells showed the greatest divergence between groups and independently predicted relapse. DN B-cell counts also correlated with circulating T peripheral helper cell numbers, supporting extrafollicular immune pathway activation. Conclusion: nGCA is characterized by outcome-dependent disturbances in B-cell homeostasis. Expansion of the DN B-cell compartment identifies a relapse-prone immunophenotype and represents a clinically relevant biomarker for early risk stratification.

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Nieto-Carvalhal, B., Monjo-Henry, I., Campos-Fabre, C., Garcia-Carazo, S., Bohorquez, C., Villalba, A., Peiteado, D., de Miguel, E., Miranda-Carus, M.-E.. 2026-10-01. Double-Negative B Cell Expansion Defines a Relapse-Prone Immunophenotype in Newly Diagnosed Giant Cell Arteritis. https://doi.org/10.64898/2026.09.25.754436

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