IgE antibodies are key mediators of antiparasitic immune responses, but their potential for cancer treatment via antibodydependent cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen-specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages; however, the underlying therapeutic mechanisms were undefined and in vivo proof of concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fce receptor system for cancer studies. We also generated rat IgE and IgG mAbs specific for the folate receptor (FRa), which is expressed widely on human ovarian tumors, along with a syngeneic rat tumor model expressing human FRa. Compared with IgG, anti-FRa IgE reduced lung metastases. This effect was associated with increased intratumoral infiltration by TNFa þ and CD80

A An nc ch ho or ri in ng g t th he e g ge en no om me e A Ab bs st tr ra ac ct t Although the principles governing chromosomal architecture are largely unresolved, there is evidence that higher-order chromatin folding is mediated by the anchoring of specific DNA sequences to the nuclear matrix. These genome anchors are also crucial regulators of gene expression and DNA replication, and play a role in pathogenesis. The electronic version of this article is the complete one and can be found online at

Objectives The Covid-19 pandemic necessitated a rapid global transition towards telemedicine; yet much remains unknown about telemedicine’s acceptability and safety in rheumatology. To help address this gap and inform practice, this study investigated rheumatology patient and clinician experiences and views of telemedicine. Methods Sequential mixed methodology combined analysis of surveys and in-depth interviews. Between and within-group differences in views of telemedicine were examined for patients and clinicians using t-tests. Results Surveys (Patients n = 1,340, Clinicians n = 111) and interviews (Patients n = 31, Clinicians n = 29) were completed between April 2021 and July 2021. The majority of patients were from the UK (96%) and had inflammatory arthritis (32%) or lupus (32%). Patients and clinicians rated telemedicine as worse than face-to-face consultations in almost all categories, although >60% found it more convenient. Building trusting medical relationships and assessment accuracy were great concerns (93% of clinicians and 86% of patients rated telemedicine as worse than face-to-face for assessment accuracy). Telemedicine was perceived to have increased misdiagnoses, inequalities and barriers to accessing care. Participants reported highly disparate telemedicine delivery and responsiveness from primary and secondary care. Although rheumatology clinicians highlighted the importance of a quick response to flaring patients, only 55% of patients were confident that their rheumatology department would respond within 48 hours. Conclusion Findings indicate a preference for face-to-face consultations. Some negative experiences may be due to the pandemic rather than telemedicine specifically, although the risk of greater diagnostic inaccuracies using telemedicine is unlikely to be fully resolved. Training, choice, careful patient selection, and further consultation with clinicians and patients is required to increase telemedicine’s acceptability and safety.

The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the threedimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

Objective To explore the impact of patient-physician interactions, pre- and post-diagnosis, on lupus and undifferentiated connective tissue disease (UCTD) patients’ psychological well-being, cognitions and healthcare-seeking behaviour. Methods Participants were purposively sampled from the 233 responses to a survey on patient experiences of medical support. Twenty-one semi-structured interviews were conducted and themes generated using thematic analysis. Results The study identified six principal themes: 1. The impact of the diagnostic journey; 2. The influence of key physician(s) on patient trust and security, with most participants reporting at least one positive medical relationship; 3. Disparities in patient-physician priorities, with patients desiring more support with Quality of Life (QoL) concerns; 4. Persisting insecurity and distrust, which was prevalent, and largely influenced by previous and anticipated disproportionate (often perceived as dismissive) physician responses to symptoms, and experiences of widespread inadequate physician knowledge of systemic autoimmune diseases; 5. Changes to healthcare-seeking behaviours, such as curtailing help-seeking or under-reporting symptoms; and 6. Empowerment, including shared medical decision making and knowledge acquisition, which can mitigate insecurity and improve care. Conclusion Negative medical interactions pre- and post- diagnosis can cause a loss of self-confidence and a loss of confidence and trust in the medical profession. This insecurity may persist even in subsequent positive medical relationships and should be addressed. Key physicians implementing empowering and security-inducing strategies, including being available in times of health crises and validating patient- reported symptoms, may lead to more trusting medical relationships and positive healthcare-seeking behaviour.

The folding of chromatin into topologically constrained loop domains is essential for genomic function. We have identified genomic anchors that define the organization of chromatin loop domains across the human major histocompatibility complex (MHC). This locus contains critical genes for immunity and is associated with more diseases than any other region of the genome. Classical MHC genes are expressed in a cell type-specific pattern and can be induced by cytokines such as interferon-gamma (IFNG). Transcriptional activation of the MHC was associated with a reconfiguration of chromatin architecture resulting from the formation of additional genomic anchors. These findings suggest that the dynamic arrangement of genomic anchors and loops plays a role in transcriptional regulation.

Objective The UK’s shielding guidance for the ‘clinically extremely vulnerable’ (CEV) commenced on 23 March 2020 in response to the COVID-19 pandemic. The purpose of this study was to explore the impact of the pandemic and shielding on patients with lupus and related systemic autoimmune rheumatic diseases (SARDs). Methods This was a mixed-methods cohort study (N = 111) including pre-lockdown baseline surveys (March 2020), follow-up surveys (June 2020), and in-depth interviews during July 2020 (N = 25). Results Most participants had a high level of anxiety regarding their mortality risk from COVID-19 and supported the shielding concept. Shielding allocations and communications were perceived as inconsistently applied and delivered. Over half of those not classified as CEV reported feeling abandoned, at increased risk and with no support. Shielding communications increased feelings of being ‘cared about’, yet also increased fear, and the ‘vulnerable’ labelling was perceived by some to damage social- and self-identity. Over 80% of those classified as CEV stated that the classification and subsequent communications had changed their social-mixing behaviour. Despite many negative impacts of COVID-19 and shielding/lockdown being identified, including isolation, fear and reduced medical care, the during-pandemic quantitative data showed increases in most measures of well-being (which was low at both timepoints) from pre-lockdown, including reductions in the impact of fatigue and pain (Ps < 0.001). Conclusion Shielding classifications and communications were generally positively viewed, although perceived as inconsistently delivered and anxiety-provoking. More frequent positively-framed communication and wellbeing support could benefit all SARD patients. Slower-paced ‘lockdown’ lifestyles may confer health/wellbeing benefits for some people with chronic diseases.

Objective To explore the self-reported impact of the COVID-19 pandemic on changes to care and behaviour in UK patients with systemic autoimmune rheumatic diseases, to help ensure that patient experiences are considered in future pandemic planning. Methods This was a longitudinal mixed methods study, with a cohort completing baseline surveys in March 2020 and follow-up surveys in June 2020 (N = 111), combined with thematic analysis of the LUPUS UK forum and participant interviews (N = 28). Results Cancellations of routine care and difficulties accessing medical support contributed to some participants deteriorating physically, including reports of hospitalisations. The majority of participants reported that fear of COVID-19 and disruptions to their medical care had also adversely impacted their mental health. Feeling medically supported during the pandemic correlated with multiple measures of mental health and perceptions of care, including the Warwick-Edinburgh Mental Wellbeing Score (r = 0.44, p = 0.01). Five themes were identified: 1. Detrimental reduction in care; 2. Disparities in contact and communication, (medical security vs abandonment sub-theme); 3. Perceived and actual endangerment; 4. The ‘perfect storm’ of reduced clinician ability to help, and increased patient reticence to seek help; and 5. Identifying the patients most vulnerable to reduced medical care. Conclusion The diversion of resources away from chronic disease care was perceived by many participants to have caused adverse outcomes. Fear about increased vulnerability to COVID-19 was high, contributing to healthcare-avoidant behaviours. This study also highlights the influence of clinician accessibility and patients feeling medically supported on multiple measures of physical and mental health.