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Preprint WatchStrongOctober 2nd, 2026

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.

Giant cell arteritis, traditionally read as T cell driven, shows a pathogenic B cell contribution, and expansion of the CD27-negative IgD-negative double-negative B cell compartment at diagnosis independently predicted relapse at twelve months in 55 followed patients, correlating with T peripheral helper cell counts and implicating extrafollicular activation.

Strong contradiction

5 prior failures

Three or more documented clinical failures match this mechanism, or a Phase 3 efficacy failure is on record.

This preprint nominates the B cell compartment as pathogenic and prognostic in a disease long read as T cell driven, and it is worth reading against five recorded CD19 failures in the Claidex graph. Two are efficacy failures of the same CD19-directed molecule in autoimmune disease, LY3541860 in rheumatoid arthritis (ly3541860-cd19-rheumatoid-arthritis-phase2a-efficacy-failure) and in relapsing multiple sclerosis (ly3541860-cd19-relapsing-multiple-sclerosis-phase2a-2b-efficacy-failure), and two are sponsor discontinuations of CD19 CAR-T in lupus nephritis (kyv-101-cd19-car-t-refractory-lupus-nephritis-kysa-1-strategic-reprioritization) and diffuse cutaneous systemic sclerosis (kyv-101-cd19-car-t-diffuse-cutaneous-systemic-sclerosis-kysa-5-strategic-reprioritization). The caveat matters: this preprint uses CD19 as a lineage marker for flow cytometry and does not nominate it as a drug target, so the cross-reference is at the level of the therapeutic hypothesis rather than the molecule. The transferable point is that broad CD19-directed depletion has twice failed on efficacy in autoimmune indications, while this work localises the signal to a specific double-negative subset. A programme acting on these data should ask whether depleting that subset is achievable with a pan-B-cell agent before repeating the design that failed.

Abstract excerpt

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.

Matching Claidex post-mortems

4 of 4 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.