Biology subjects

Nieto-Carvalhal, B.

Publications and source records attributed to Nieto-Carvalhal, B..

2 recordsLinked to original sources

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↗

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↗