Biology subjects

Peiteado, D.

Publications and source records attributed to Peiteado, D..

2 recordsLinked to original sources

bioRxiv2026

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

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.

immunology↗

bioRxiv2023

Increased circulating CD39+FoxP3+CD4+ regulatory T cells in Early Rheumatoid Arthritis facilitate the antiinflammatory action of methotrexate and associate with the clinical response

OBJECTIVESFoxP3+ regulatory T cells (Tregs) are key to the immune system homeostasis; their CD39+ subset (Treg39+) hydrolises adenine nucleotides released by stressed cells, rendering the antiinflammatory adenosine. Methotrexate (MTX), inhibiting AICAR transformylase (ATIC), enhances the extrusion of adenine nucleotides and hence may help Treg39+ cells control inflammation. Therefore, we examined the relation of CD39 expression on Tregs of early RA (ERA) patients with the effect of MTX. METHODSFreshly isolated lymphocytes from 72 untreated ERA patients (duration <24 weeks) and 72 healthy controls (HCs) were examined by cytometry. Treg cell potency was assessed in cocultures of CD4+CD25+CD127- Treg with CD4+CD25- CD127+ responder T cells (Tresp). RESULTSERA patients demonstrated a superior frequency of circulating Tregs containing increased proportions of Treg39+ cells. Total ERA Tregs were more potent than HC Tregs and MTX further heightened their potency, with greater amplification in ERA vs HC; differences were reduced by adenosine pathway blockade. The potency of isolated Treg39+ and its enhancement by MTX were comparable for ERA and HC suggesting that the differences seen with total Tregs are due to the increased ERA Treg39+ frequency. Basal Treg39+ cell proportions > 39.3 associated with a good 12 month EULAR response [RR 13.4 (2.9-75.6)]. At 12 months, the ERA Treg39+ frequency had decreased to HC levels but its association with the clinical response remained. CONCLUSIONMTX cooperates with Treg39+ cells and the basal Treg39+ frequency is a predictor of clinical response. The increased circulating Treg39+ cells in untreated ERA would further facilitate the action of MTX thereby providing a slot for prompt MTX initiation.

immunology↗