Biology subjects

de Miguel, E.

Publications and source records attributed to de Miguel, E..

3 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↗

bioRxiv2024

Circulating PD-1hi CXCR5- and CXCR5+ CD4 T cells are elevated in patients with newly diagnosed Giant Cell Arteritis and predict relapse

BACKGROUNDGiant cell arteritis (GCA) is a large/medium-vessel granulomatous vasculitis, and the PD-1/PD-L1 coinhibitory pathway seems to be implicated in its pathogenesis. CD4 T cells expressing high PD-1 levels, CD4+CXCR5-PD-1hi peripheral helper (Tph) and CD4+CXCR5+PD-1hi follicular helper T cells (Tfh), are key mediators of autoimmunity. Their frequencies are elevated in the peripheral blood of subjects with several autoimmune conditions but have not been investigated in GCA. Our objective was to study the frequency of circulating Tph (cTph) and Tfh (cTfh) in patients with newly diagnosed GCA (nGCA). METHODSProspective, non-interventional study on consecutive patients referred to our ultrasound GCA fast-track clinic over a period of 24 months. Peripheral blood was drawn immediately upon initial diagnosis. For each patient, an age and gender-matched healthy control (HC) was included. PBMCs isolated by Ficoll-Hypaque were examined by cytometry. Patients were subsequently treated with standard therapy according to the updated 2018 EULAR recommendations. RESULTS65 nGCA patients were included. As compared with HC, nGCA patients presented at baseline with an increased frequency of cTph and cTfh cells. Among the 46 patients who could be followed up for 12 months, 19 experienced a relapse. The baseline frequency of cTph and cTfh cells had been significantly lower in patients who relapsed as compared with those who did not. A cTph cell frequency <0.56 predicted relapse with a sensitivity of 90% and specificity of 93%. CONCLUSIONnGCA patients demonstrate increased baseline cTph and cTfh cell frequencies. Lower baseline proportions of cTph and cTfh cells associate with relapse.

immunology↗

bioRxiv2020

Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area

The cellular architecture of the ventral tegmental area (VTA), the main hub of the brain reward system, remains only partially characterized. To extend the characterization to inhibitory neurons, we have identified three distinct subtypes of somatostatin (Sst)-expressing neurons in the mouse VTA. These neurons differ in their electrophysiological and morphological properties, anatomical localization, as well as mRNA expression profiles. Importantly, similar to cortical Sst-containing interneurons, most VTA Sst neurons express GABAergic inhibitory markers, but some of them also express glutamatergic excitatory markers and a subpopulation even express dopaminergic markers. Furthermore, only some of the proposed marker genes for cortical Sst neurons were expressed in the VTA Sst neurons. Physiologically, one of the VTA Sst neuron subtypes locally inhibited neighboring dopamine neurons. Overall, our results demonstrate the remarkable complexity and heterogeneity of VTA Sst neurons and suggest that these cells are multifunctional players in the midbrain reward circuitry.

neuroscience↗