Plenary I: Rheumatic Disease During Pregnancy Can Increase Cardiovascular Risk 18-Fold

Autoimmune rheumatic disease (ARD) and pregnancy are both known to increase the risk of cardiovascular events (CVEs), but there are only a few studies that have examined the impact of ARDs on maternal cardiovascular health during and shortly after pregnancy. A new study to be presented during Plenary I found that lupus with antiphospholipid syndrome can increase the risk of by CVEs 18-fold during pregnancy.

CVEs are six times as likely with systemic lupus erythematous (SLE) and nearly three times as likely with rheumatoid arthritis.

“It is recognized that CVEs are higher in the rheumatic disease population in general even without pregnancy,” said Rashmi Dhital, MD, Postdoctoral Fellow in Rheumatology, Allergy & Immunology at the University of California, San Diego School of Medicine. “Adding pregnancy to the mix adds to that risk.”

Dr. Dhital will present the first of five abstracts during Plenary I on Sunday, Nov. 12, from 11 a.m.–12:30 p.m. PT in Exhibit Hall A–B of the San Diego Convention Center. The session will be livestreamed and will be available on demand within 24 hours for registered ACR Convergence 2023 participants.

Dr. Dhital reviewed administrative data on individuals who were pregnant and delivered singleton live births in California between 2005 and 2020 to identify ARDs and CVEs during pregnancy and up to six weeks postpartum. The presence of any ARD increased the risk of any acute CVE fourfold compared to the risk in individuals who were pregnant and did not have ARDs.

“The results highlight the need for standardized guidelines and evidence-based practices to screen for cardiovascular risk in pregnant patients with ARDs,” Dr. Dhital said. “Adding cardiovascular risk screening and management to our existing ACR reproductive health guideline would be an important benefit to our patients with ARDs who are pregnant or are considering pregnancy.”

TRAF5, pulmonary arterial hypertension, and SLE

Pulmonary arterial hypertension (PAH) is a significant complication in SLE patients that is characterized by rapid progression and poor prognosis. While the pathogenesis of PAH in SLE is unclear, it appears to be a combination of inflammation and genetic abnormalities that can lead to dysfunction of pulmonary artery endothelial cells (PAEC), cellular proliferation, and pulmonary vascular remodeling. Multiple genetic studies of peripheral blood from SLE-PAH patients and a novel animal model of SLE-PAH suggest that tumor necrosis factor receptor-associated factor 5 (TRAF5) could be both a diagnostic biomarker for SLE-PAH and a potential therapeutic target.

“We used whole exome sequencing and a genome-wide association study of peripheral blood from SLE patients who have PAH to identify TRAF5 as a gene that is active in the pathogenesis of SLE-PAH,” said Xiaoyue Deng, PhD, Postdoctoral Fellow of Rheumatology and Clinical Immunology at Peking Union Medical College Hospital, Beijing, China. “We designed a mouse model that demonstrated both the lupus phenotypes and PAH symptoms, very much like our patients. When we gave the model overexpression of TRAF5 by injecting an overexpression vector, we saw an increase in TRAF5 and a marked decrease in PAH symptoms.”

TRAF5 appears to modulate the transforming growth factor (TGF) beta signaling pathway to induce PAEC dysfunction, although the precise mechanism remains unknown, Dr. Deng said.

“It will be a long way to clinical application, but we see TRAF5 levels in peripheral blood as a potential biomarker for SLE-PAH,” he explained. “And maybe we can find a TRAF5-associated pathway to target to finally give us some management possibilities for SLE-PAH.”

Sexually dimorphic gene expression of synovial macrophages in RA

It has long been recognized that rheumatoid arthritis (RA) has a female bias, but the mechanism has not been clear. Recent work in single-cell RNA sequencing (scRNAseq) suggests that specific subtypes of synovial macrophage could play a role in the pathogenesis of RA. A novel mouse model of RA found that specific myeloid synovial subsets show a significant female bias that maps to human RA.

“The epidemiology of RA is very clear, but there aren’t any sex-specific therapies and not many preclinical models to study sex differences,” said Richard Bell, PhD, Postdoctoral Fellow at the Hospital for Special Surgery. “Some existing models may have sex differences, but this is an understudied area. We have characterized one sexually dimorphic model and shown its relevance in human RA.”

Researchers analyzed myeloid scRNAseq data from the Accelerating Medicines Partnership-RA consortium with about 76,000 cells from human synovial biopsies. Differential gene expression and gene set enrichment analysis identified macrophage subsets showing female bias. Similar sex-based bias of the same subsets was seen in a mouse model of RA.

“We have known about the sex bias in RA for 40, 50 years, yet very little progress has been made,” Dr. Bell said. “This is one step forward to help understand the disease in a more fundamental way and understand how biologic sex influences disease risk. And maybe we will eventually have a therapy that can modulate sex-specific factors.”

Reduced-dose glucocorticoid regimen in severe GPA or MPA associated with increased risk of death, ESKD, and progression

A multicenter, real-world retrospective study comparing the PEXIVAS reduced-dose glucocorticoid (GC) regimen versus standard treatment for patients with severe granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) found that the reduced-dose regimen is associated with a composite of death, end-stage kidney disease (ESKD), and progression at one year. The study explores a subgroup analysis of PEXIVAS that suggested a trend toward increased risk of death or ESKD in patients treated with rituximab.

The PEXIVAS follow-up study will be presented by Sophie Nagle, MD, Université Paris-Saclay, France.

Consensus recommendations for musculoskeletal ultrasound education in Canada

Canada has its first-ever expert consensus recommendations for musculoskeletal ultrasound (MSUS) education in residency training programs.

“The Royal College of Physicians and Surgeons, the governing body of residency education in Canada, recently added training in MSUS to the core competencies in rheumatology, similar to the Accreditation Council of Graduate Medical Education recommendation for rheumatology residents in the United States. But especially in Canada, there is no current standard for what competencies should be taught. There is a huge variety in terms of what residents are learning,” said Maria Powell, MD, Fellow in Training at the University of Calgary Cumming School of Medicine, Calgary, Canada.

MSUS experts in Canada and the US agreed on a list of 42 mandatory MSUS competencies and 39 optional competencies. Dr. Powell said the recommendations are a first step in standardizing MSUS residency training across Canadian medical education.

An MSUS working group recommended mandatory training in basic ultrasound skills for all residents in Canada that would cover:

• How to perform a focused MSUS exam of the hands, wrists, and feet for features of inflammatory arthritis including effusion, synovitis (grey scale and power Doppler), bone erosion versus osteophyte, and tenosynovitis; and
• How to perform a limited MSUS exam of the knee and ankle to identify joint effusion.

“Musculoskeletal ultrasound in rheumatology has multiple clinical benefits as well as educational advantages and is an exciting area of ongoing research,” said Dr. Powell. “Residency is an ideal time to learn this skill.