Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, although several evidences also demonstrate a B cell involvement in its etiology. Follicular T helper (Tfh) cells, a CXCR5-expressing CD4+ T cell subpopulation, are essential in the regulation of B cell differentiation and maintenance of humoral immunity. Alterations in circulating (c)Tfh distribution and/or function have been associated with autoimmune diseases including MS. Dimethyl fumarate (DMF) is a recently approved first-line treatment for relapsing–remitting MS (RRMS) patients whose mechanism of action is not completely understood. The aim of our study was to compare cTfh subpopulations between RRMS patients and healthy subjects and evaluate the impact of DMF treatment on these subpopulations, relating them to changes in B cells and humoral response. We analyzed, by flow cytometry, the distribution of cTfh1 (CXCR3+CCR6−), cTfh2 (CXCR3−CCR6−), cTfh17 (CXCR3−CCR6+), and the recently described cTfh17.1 (CXCR3+CCR6+) subpopulations of CD4+ Tfh (CD45RA−CXCR5+) cells in a cohort of 29 untreated RRMS compared to healthy subjects. CD4+ non-follicular T helper (Th) cells (CD45RA−CXCR5−) were also studied. We also evaluated the effect of DMF treatment on these subpopulations after 6 and 12 months treatment. Untreated RRMS patients presented higher percentages of cTfh17.1 cells and lower percentages of cTfh2 cells consistent with a pro-inflammatory bias compared to healthy subjects. DMF treatment induced a progressive increase in cTfh2 cells, accompanied by a decrease in cTfh1 and the pathogenic cTfh17.1 cells. A similar decrease of non-follicular Th1 and Th17.1 cells in addition to an increase in the anti-inflammatory Th2 subpopulation were also detected upon DMF treatment, accompanied by an increase in naïve B cells and a decrease in switched memory B cells and serum levels of IgA, IgG2, and IgG3. Interestingly, this effect was not observed in three patients in whom DMF had to be discontinued due to an absence of clinical response. Our results demonstrate a possibly pathogenic cTfh pro-inflammatory profile in RRMS patients, defined by high cTfh17.1 and low cTfh2 subpopulations that is reverted by DMF treatment. Monitoring cTfh subsets during treatment may become a biological marker of DMF effectiveness.

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Background Percutaneous coronary intervention (PCI) in spontaneous coronary artery dissection (SCAD) should be reserved for cases presenting with ongoing extensive ischaemia. Bioresorbable scaffolds (BVS) have emerged as an alternative to avoid permanent stenting, an especially attractive concept for this clinical scenario. However, data of late angiographic outcome of this device in SCAD is lacking. Purpose To evaluate the long-term angiographic outcome of BVS in the setting of SCAD using computed tomography coronary angiography (CTCA) Methods In this multicentre prospective study, high-risk SCAD patients treated with BVS were scheduled for a follow-up CTCA at least 2 years from implantation date. Acquisition was performed according to the current recommendations. All the studies were analysed in a central core laboratory by an independent level 3 expert in CTCA blinded to the clinical and angiographic results. For this purpose, a dedicated software for coronary analysis was used to quantify coronary stenosis and evaluate coronary wall. Results Thirty-four BVS were implanted in 15 SCAD patients (51±12 years-old; 87% female) from 7 different centres in Spain and United Kingdom. The most common presentation was STEMI (n=9, 60%). Target vessels included 11 left anterior descending arteries (73.3%), 3 right coronary arteries (20%) and 1 left circumflex coronary artery (6.7%). One patient received target lesion revascularisation due to scaffold shrinkage in a proximal right coronary artery at 13 months. CTCA was performed 2.4±0.7 years after BVS implantation. No scaffold thrombosis or significant stenosis were detected. Patency of all scaffolds was confirmed with a median luminal area of 5.52 mm2 (IQR: 3.74–6.95) and median stenosis of 11% (IQR: 4–15%). Regarding coronary wall tissue characterization of segments with BVS, there was 32±9.3% of plaque burden and a median plaque volume of 45.3 mm3 (IQR: 26.6–61.9). The most common component of the plaque was fibrous (85±9.4%). Compared to the proximal reference segments, BVS showed more plaque burden (32.2% vs 25.3%; p=0.017) and fibrous percentage (84.7% vs 75.1%; p=0.004) whereas less fibrofatty (6 vs 4.8 mm3; p=0.007) and necrotic volume (0.4 vs 1.2 mm3; p=0.029). BVS segments showed lower absolute minimal luminal area (5.5 vs 8.9 mm2; p=0.004) and diameter (2.7 vs 3.4 mm; p=0.004) compared to the reference segment; however, non-significant differences were seen in percentage stenosis, in keeping with normal vessel tapering. Conclusions In this series of SCAD treated with BVS, scaffolds showed a satisfactory late angiographic outcome, with no significant restenosis and an excellent minimal luminal area and optimal coronary wall healing observed. Funding Acknowledgement Type of funding source: None