An Autoreactive Antibody from an SLE/HIV-1 Individual Broadly Neutralizes HIV-1

Broadly HIV-1–neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1–infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1–infected individual with SLE who exhibited controlled viral load (\u3c5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient’s plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells

How Well Do Rheumatology Fellows Manage Acute Infusion Reactions? A Pilot Curricular Intervention

Background Infusible DMARDs are commonly prescribed in rheumatology and other fields. There are no published formal educational curricula rheumatology fellowship programs can use to teach infusion reaction management skills to fellows. We aimed to better understand this educational gap, and implement and assess the effectiveness of an experiential curriculum on acute infusion reaction management. Methods We included current rheumatology fellows and recent graduates from five fellowship programs. Using a novel behavioral checklist we assessed fellows’ performance managing an infusion reaction in a simulation, followed by a didactic focused on infusion reactions. Pre and post-surveys assessed experiences to determine relevance, as well as attitudes and knowledge. Results Despite ubiquitous prescribing of infusible biologic DMARDs, \u3e50% of fellows were uncomfortable managing infusion reactions. Only 11% of fellows reported infusion reaction training during fellowship, but 56% reported managing actual patient infusion reactions. In the simulated infusion reaction, fellows managed grade 1 reactions appropriately, but grade 4 reactions poorly, meeting \u3c50% of objectives. All fellows discontinued the infusion in the setting of anaphylaxis, but only 56% administered epinephrine. There was no difference in performance or written knowledge by training year. All fellows felt more prepared to manage infusion reactions post-curriculum and were satisfied with the experience. Conclusion We confirmed an education gap in rheumatology fellowship training regarding infusion reactions, both in knowledge and performance. We developed and implemented a brief experiential curriculum including simulation of a high-risk patient care scenario. This curriculum was well received and is easily exportable to other programs

Mönckeberg sclerosis with giant cells as a masquerade of giant cell arteritis

Giant cell arteritis (GCA) is the most common type of vasculitis in adults, which is classified as a large/medium vessel vasculitis. It has a predilection for the ophthalmic circulation and extracranial carotid system. Temporal artery biopsy specimens can show the presence of inflammatory multinucleated giant cells. Here, we report just the third case of Mönckeberg sclerosis with multinucleated giant cells affecting the temporal artery and mimicking GCA. This rare finding in the evaluation of a common vasculitis is important for rheumatologists to be aware of and emphasizes close collaboration between clinicians and pathologists

Incorporating Telemedicine in Rheumatology Fellowship Training Programs: Needs Assessment, Curricular Intervention, and Evaluation

OBJECTIVE: To increase rheumatology fellows\u27 in training (FITs) confidence in delivering virtual care (VC) and prepare them for independent practice, we developed educational materials addressing gaps in their skills. METHODS: We identified gaps in telemedicine skills based on FIT performance in a virtual rheumatology observed structured clinical examination (vROSCE) station on VC delivery using videoteleconference technology and survey (Survey1) responses. We created educational materials including videos of mediocre and excellent VC examples, discussion/reflection questions, and a document summarizing key practices. We measured change in FITs\u27 confidence levels for delivering VC with a post-intervention survey (Survey2). RESULTS: Thirty-seven FITs (19 first-year, 18 second + third-year fellows) from seven rheumatology fellowship training programs participated in a vROSCE and demonstrated gaps in skills mapping to several Rheumatology Telehealth Competency domains. FITs\u27 confidence levels improved significantly from Survey1 to Survey2 for 22 of 34 (65%) questions. All participating FITs found the educational materials helpful for learning and reflecting on their own VC practice; 18 FITs (64%) qualified usefulness as moderately or a lot . Through surveying, 17 FITs (61%) reported implementing skills from the instructional videos into VC visits. DISCUSSION: Continually assessing our learners\u27 needs and creating educational materials addressing gaps in training is requisite. Using a vROSCE station, needs assessments, and targeted learning with videos and discussion-guidance materials enhanced the confidence level for FITs in VC delivery. It is imperative to incorporate VC delivery into fellowship training program curricula to ensure breadth in skills, attitudes, and knowledge of new entrants into the rheumatology workforce. This article is protected by copyright. All rights reserved

Virtual Learning and Assessment in Rheumatology Fellowship Training: OSCE Revisited

OBJECTIVE: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face Rheumatology Objective Structured Clinical Examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the six Accreditation Council for Graduate Medical Education (ACGME) Core Competencies for fellows-in-training (FITs). This report describes the novel design, feasibility, and stakeholder value of a vROSCE. METHODS: Through an established collaboration of five rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom® platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience. RESULTS: Twenty-three rheumatology FITs from 5 institutions successfully rotated through six stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME Core Competencies. Sixty-five percent (15/23) of FITs responded to the survey. Ninety-three percent of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement. CONCLUSIONS: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched Rheumatology FITs\u27 education and offered collaborative learning experiences across institutions. This article is protected by copyright. All rights reserved

Using PROMIS-29 to determine symptom burdens in the context of the Type 1 and 2 systemic lupus erythematosus (SLE) model: a cross sectional study

Abstract Objective To account for heterogeneity in systemic lupus erythematosus (SLE) and bridge discrepancies between patient- and physician-perceived SLE activity, we developed the Type 1 and 2 SLE model. We examined PROMIS-29 scores, a composite patient-reported outcome (PRO) measure, through the lens of the model. Methods Patients completed PROMIS-29 and the polysymptomatic distress scale (PSD). Rheumatologists completed the SLE disease activity index (SLEDAI), and physician’s global assessments (PGAs) for Type 1 and 2 SLE. We defined Type 1 SLE using SLEDAI, Type 1 PGA, and active nephritis, and Type 2 SLE using PSD and Type 2 PGA. We compared PROMIS-29 T-scores among Type 1 and 2 SLE groups and explored whether PROMIS-29 can predict Type 1 and 2 SLE activity. Results Compared to the general population, patients with isolated Type 1 SLE reported greater pain and physical dysfunction but less depression and improved social functions; patients with high Type 2 SLE (irrespective of Type 1 activity) reported high levels of pain, fatigue, and social and physical limitations. Patients with minimal Type 1 and 2 SLE had less depression and greater physical functioning with other domains similar to national norms. PROMIS-29 predicted Type 2 but not Type 1 SLE activity. Conclusion PROMIS-29 similarities in patients with high Type 2 SLE, with and without active Type 1 SLE, demonstrate the challenges of using PROs to assess SLE inflammation. In conjunction with the Type 1 and 2 SLE model, however, PROMIS-29 identified distinct symptom patterns, suggesting that the model may help clinicians interpret PROs

Intermittent and Persistent Type 2 lupus: patient perspectives on two distinct patterns of Type 2 SLE symptoms

Objective We have developed a new conceptual model to characterise the signs and symptoms of SLE: the Type 1 and 2 SLE Model. Within the original model, Type 1 SLE consists of inflammatory manifestations like arthritis, nephritis and rashes; Type 2 SLE includes symptoms of fatigue, myalgia, mood disturbance and cognitive dysfunction. Through in-depth interviews, we explored how the Type 1 and 2 SLE Model fits within the lived experience of patients with SLE, with a focus on the connection between Type 1 and Type 2 SLE symptoms.Methods Semistructured in-depth interviews were conducted among adult participants meeting 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria for SLE. Participants were purposefully selected for age, race, sex and nephritis history. All interviews were audio-recorded and transcribed. Data were analysed through episode profile and thematic analysis.Results Through interviews with 42 patients with SLE, two patterns of Type 2 SLE emerged: Intermittent (n=18) and Persistent (n=24). Participants with Intermittent Type 2 SLE described feeling generally well when Type 1 is inactive; these participants were younger and had more internal SLE manifestations. Participants with Persistent Type 2 described always experiencing Type 2 symptoms despite inactive Type 1, although the severity may fluctuate. Participants with Persistent Type 2 SLE experienced traditional lupus symptoms of joint pain, hair loss and rash, but less often had severe organ system involvement.Conclusions By listening to the stories of our patients, we found two underlying patterns of Type 2 SLE: Intermittent Type 2 symptoms that resolve in synchrony with Type 1 inflammatory symptoms, and Persistent Type 2 symptoms that continue despite remission of Type 1 symptoms

Randomized, Double‐Blind, Placebo‐Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus

ObjectiveVitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE.MethodsSLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level ≤20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed.ResultsBaseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were similar. Repletion of 25(OH)D (i.e., levels ≥30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n = 40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D3 was well tolerated, and there were no safety concerns.ConclusionVitamin D3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes