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Characterization of the human EBV-specific CD4+ T cell response using MHC II tetramers reveals the latent EBV antigen response is more frequent than the lytic response with a delayed EBNA1 response that coincides with diminished cross-presentation.

Epstein-Barr virus (EBV), a B-lymphotropic herpesvirus, encodes 2 immediate early (IE), >30 early (E) and >30 late (L) phase proteins during its replication (lytic) cycle. Despite this, lytic antigen-induced CD8 responses are strongly skewed towards IE and a few E proteins only, all expressed before HLA I presentation is blocked in lytically-infected cells. For comparison, here we (i) examined CD4+ T cell responses to 8 IE, E or L proteins, screening 14 virus-immune donors to overlapping peptide pools in interferon-gamma Elispot assays, and (ii) established CD4+ T cell clones against 12 defined epitopes for target recognition assays. We find that the lytic antigen-specific CD4+ T cell response differs radically from its CD8 counterpart in that (i) it is widely distributed across IE, E and L antigen targets, often with multiple reactivities detectable per donor and with either IE, E or L epitope responses being numerically dominant, and (ii) all CD4+ T cell clones, whether IE, E or L epitope-specific, show strong recognition of EBV-transformed B cell lines despite the lines containing only a small fraction of lytically-infected cells; efficient recognition occurs because lytic antigens are released into the culture, then acquired and processed by neighbouring latently-infected cells. These findings suggest that (i) lytic antigen-specific CD4 responses are driven by a different route of antigen display than drives CD8 responses, and (ii) such CD4 effectors could be therapeutically useful against EBV-driven lymphoproliferative disease lesions, which contain similarly small fractions of EBV-transformed cells entering lytic cycle.

Recruitment into clinical research studies is a major challenge. This study was carried out to explore the perceptions and attitudes towards clinical research participation among the general public in Qatar. A population based questionnaire study was carried out at public events held in Qatar. Residents of Qatar, 18 years or above in age were surveyed, anonymously, following verbal consent. Descriptive and multivariate analyses were conducted. We administered 2517 questionnaires to examine clinical research participation, of which 2379 complete forms were analyzed. Those who had previously been approached to participate in research completed a more detailed assessment. Data showed that only 5.7% participants (n = 134) had previously been approached to participate in a clinical research study. Of these 63.4% (n = 85) had agreed to participate while 36.6% (n = 49) had declined. The main reasons for declining participation included: time constraint (47.8%, n = 11), ‘fear’ (13.0%, n = 3), lack of awareness about clinical research (8.7%, n = 2) and lack of interest (8.7%, n = 2). ‘To help others’ (31.8%, n = 27) and ‘thought it might improve my access to health care’ (24.7%, n = 21) were the prime motivators for participation. There was a general agreement among participants that their previous research experience was associated with positive outcomes for self and others, that the research conduct was ethical, and that opportunities for participation will be welcomed in future. More than ten years of stay within Qatar was a statistically significant determinant of willingness to participate, adjusted odds ratio 5.82 (95% CI 1.93–17.55), p = 0.002. Clinical research participation in Qatar needs improvement. Time constraints, lack of trust in and poor awareness about clinical research are main barriers to participation. Altruism, and improved health access are reported as prime motivators. Deeper insight in to the factors affecting clinical research participation is needed to devise evidence based policies for improvement in recruitment strategies.

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Objective: This study aimed to determine the effect of reperfusion therapies on the occurrence of early post-stroke seizures (PSS) in patients with acute ischemic stroke (AIS).Background: Reperfusion therapies are paramount to the treatment of stroke in the acute phase. However, their effect on the incidence of early seizures after an AIS remains unclear.Design and Methods: The stroke database at Hamad Medical Corporation was used to identify all patients who received reperfusion therapies for AIS from 2016 to 2019. They were matched with patients of similar diagnosis, gender, age, and stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS) who did not receive such treatment. The rates of early PSS were calculated for each group.Results: The results showed that 508 patients received reperfusion therapies (342 had IV thrombolysis only, 70 had thrombectomies only, and 96 had received both), compared with 501 matched patients receiving standard stroke unit care. Patients who received reperfusion therapies were similar to their matched controls for mean admission NIHSS score (9.87 vs. 9.79; p = 0.831), mean age (53.3 vs. 53.2 years; p = 0.849), and gender distribution (85 vs. 86% men; p = 0.655). The group receiving reperfusion therapies was found to have increased stroke cortical involvement (62 vs. 49.3%, p < 0.001) and hemorrhagic transformation rates (33.5 vs. 18.6%, p < 0.001) compared with the control group. The rate of early PSS was significantly lower in patients who received reperfusion therapies compared with those who did not (3.1 vs. 5.8%, respectively; p = 0.042). When we excluded seizures occurring at stroke onset prior to any potential treatment implementation, the difference in early PSS rates between the two groups was no longer significant (2.6 vs. 3.9%, respectively; p = 0.251). There was no significant difference in early PSS rate based on the type of reperfusion therapy either (3.2% with thrombolysis, 2.9% with thrombectomy, and 3.1% for the combined treatment, p = 0.309).Conclusions: Treatment of AIS with either thrombectomy, thrombolysis, or both does not increase the risk of early PSS.