ACR 2026 Day 3 Report Save

Today the ACR began with the Great Debate, an intriguing set of Plenary presentations, a never-ending poster hall and a plethora of stimulation oral presentation sessions. Here are a few of my favorites from today:

• Son of Vexas ! A New Disease - Clonal Lymphoid Vasculitis With Somatic SYK Rearrangements: (Abstract 2889) (Thanks to Dr. Peter Grayson for bringing this to my attention!)  Dr. Benjamin Turturice (NIAMS/NIH) presented what may be the most important discovery of the meeting, work that has been accepted for publication in the New England Journal of Medicine (but wasn't a plenary at ACR27). Colleagues at the NIH identified 5 unrelated patients who presented with a hypereosinophilic syndrome and a distinctive systemic vasculitis (with multiple aneurysms in medium-sized arteries) that was associated with an aberrant clonal T-cell population. These patients were part of a cohort of lymphocytic-variant hypereosinophilic syndrome (L-HES) carrying aberrant clonal CD3-low CD4+ T cells and were found to have multiple aneurysms of the arteries and veins (axillary, hepatic, paraspinal, profunda femoris), plus coronary vasculitis, vertebral aneurysms and temporal arteritis, complicated by MI and stroke. Arterial biopsies showed transmural CD4+ T-cell and eosinophil infiltrates without giant cells or granulomas, and the same TCR clone was found in the inflamed artery and the blood. Whole-genome sequencing of sorted cells found that all five vasculitis patients had somatic SYK fusions (RINL-SYK or ANKS1A-SYK) that preserve the SYK kinase domain; the fusions were confined to the clonal T cells and absent from fibroblasts and normal CD4+ T cells. SYK is normally not used by T cells (ZAP70 is), yet clonal cells expressed roughly 10-fold more SYK, upregulated integrin adhesion programs and adhered avidly to matrix; inserting RINL-SYK into Jurkat T cells reproduced this, and a kinase-dead (K643R) mutant abolished it. Cytokine-directed therapy gave only partial control, while HDAC inhibition reduced the clone. Like VEXAS, this is a new molecularly defined vasculitis caused by a somatic mutation in a small blood-cell clone, here a lymphoid rather than myeloid one, in which SYK fusions steer T cells into the vessel wall. Thus far these patients have been incompletely managed with other common vasculitis drugs and there were questions as to whether fostamatinib (a SYK inhibitor) might be used in the future. Patients with L-HES or unexplained aneurysmal vasculitis may deserve lineage-specific genomic testing. In the least the diagnosis may be considered if the CD4+ or CD7+ T cells don't express CD3 by flow cytometry. Link
• Immunologic and Clinical Benefits to Lifestyle (Exercise and Weight Loss) Remodel the Aging Immune System in RA: (Abstract 2803) Dr. Hannah Maclellan (Duke) presented a secondary analysis of a pilot trial in which 20 sedentary, overweight-to-obese older adults with RA (age 60–80, BMI 28–40) were randomized to 16 weeks of remotely supervised weight loss plus exercise training (SWET) or lifestyle counseling (CHAT). The patients improved - DAS28-CRP fell 14.1% (p=0.006), patient global 45.6% (p=0.004) and swollen joints 36.6% (p=0.02). Cellular markers of immune aging also improved: naive T cells rose 7.9%, while senescent NK cells (−7.4%), total NK T cells (−19.5%) and Tregs (−11.1%) fell (all p<0.05). Interestingly, cytokine profiles, ESR, and CRP did not change. Greater disease activity improvement tracked with gains in knee extension strength (ρ=−0.57, p=0.01), muscle oxidative capacity and changes in IL-17 and IL-11, suggesting muscle–immune crosstalk. Differences between the two arms were not significant, the sample was tiny and the p values are unadjusted, so these findings are exploratory. Still, lifestyle intervention in older RA patients appears to do more than burn calories; it may reverse aspects of immunosenescence that drive disease activity. Link
• BE BOLD: Bimekizumab Beats Risankizumab in PsA Revisited: (Abstract 2804) Dr. Joseph Merola (UT Southwestern) presented these results at EULAR 2026, and reprised this important head-to-head trial (of IL-17A/F versus IL-23 inhibition in psoriatic arthritis) today at ACR 2026. BE BOLD is a double-blind phase 3b trial that randomized 553 bDMARD-naïve or TNFi-experienced (one prior TNFi) PsA patients 1:1 to bimekizumab 160 mg q4wk (320 mg if moderate-to-severe psoriasis) or risankizumab 150 mg at weeks 0, 4 and 16. Bimekizumab was superior for the primary endpoint: ACR50 at week 16 was 49.1% vs 38.0% (p=0.0058), with separation as early as week 4 (nominal p<0.0001) and an advantage sustained at week 24 (nominal p=0.0059). Interestingly, several secondary outcomes were not significant, but showed a numeric advantage for BKZ or RKZ. This included minimal disease activity, PASI and DAPSA. Serious adverse events were 1.8% vs 3.3%; Candida infections were more common with bimekizumab but all were mild to moderate, mucosal and none led to discontinuation. For PsA joint disease, dual IL-17A/F blockade demonstrated an ACR50 advantage over IL-23 inhibition in this novel head to head trial between these two competing classes in PsA. Link
• Neuropsychiatric SLE and the 2025 ACR Lupus Guideline. In a session dedicated to Lupus Guidelines, Dr. Maria Dall’Era (UCSF) reviewed her clinical and diagnostic approach to patients with Neuropsychiatric SLE (NPSLE) by discussion a 21-year-old student with SLE and psychosis. The pathogenesis of NPSLE lies in either ischemic vascular disease (thrombosis, vasculopathy, vasculitis) or an inflammation (blood–brain barrier disruption, brain-reactive antibodies, cytokines, complement, microglia), and the first step is always to exclude mimics and non-lupus causes: infection, metabolic derangement, severe hypertension, drugs and toxins, PRES, and NMOSD (AQP4-IgG ~80% sensitive) or MOGAD, both of which cause longitudinally extensive myelitis and optic neuritis. Tests help but cannot prove the diagnosis of NPSLE but can exclude other etiologies. This is primarily so for brain imaging where the MRI is often normal (in 42% of 74 first-episode NPSLE patients). Her pearl: no laboratory or imaging study is sensitive or specific enough to confirm attribution to lupus. Labs are often unrevealing. Anti-ribosomal P (present in up to 46% of SLE) is linked to psychosis and depression, and antiphospholipid antibodies to stroke, chorea, seizures, myelopathy and cognitive decline. Notably, NPSLE is excluded from phase 2/3 trials, and is hence a missed opportunity. There is limited treatment evidence from two small RCTs: adding IV cyclophosphamide to steroids raised response rates to 95% vs 46% (32 patients; Barile-Fabris, 2005) and 62% vs 22% (60 patients; Stojanovich, 2003). These and expert opinion informed the most recent ACR guideline that conditionally recommends:
  • Optic neuritis, acute confusional state and mononeuritis multiplex: pulse/high-dose steroids plus IV cyclophosphamide, mycophenolate or anti-CD20 therapy.
  • Myelitis: steroids plus IV cyclophosphamide.
  • Psychosis and seizures: antipsychotic or anti-seizure therapy plus immunosuppression.
  • Isolated cognitive dysfunction: cognitive therapy without immunosuppression.

NPSLE is a clinical diagnosis of exclusion; once it is made, inflammatory disease deserves steroids plus a real immunosuppressant, but cognitive complaints alone do not. Guideline