Immunology

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Review of HLA-B27

Jack Cush, MD

HLA-B27 remains the dominant genetic link to spondyloarthritis (SpA) across the age spectrum, but B27 related clinical expression diverges between children and adults. New mechanistic data on autoreactive T cells, HLA-B27 misfolding, and gut-joint trafficking point to new plausible, targetable

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Waist size matters! Using NHANES data (1999-2018) the weight-adjusted waist index (WWI) calculated on 5582 CKD pts. WWI was signif assoc w/ all-cause mortality (adj HR  1.17) & CV (1.24); these assoc partially mediated by NLR (inflammation) ~6.6%, showing both central adiposity https://t.co/kNf4nqiD2a
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Leeds study of 44 patients idiopathic inflamm myopathy (IIM) pts Rx w/ rituximab showed a 70% response 4-6 mos post RTX. Responders had higher TIS (50·0 vs 17·5). Using highly sensitive flow cytometry, @ 2 wks responders had lower #s memory B cells & Plasmablasts. Is there a role https://t.co/JDvVZ1KEIY
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True or False: In a Leeds study of idiopathic inflammatory myopathy patients treated with rituximab, responders had lower memory B cells and plasmablasts at 2 weeks. See if you got it right in this week's RheumIQ quiz at https://t.co/UaXqHKWizt. https://t.co/zRJOMeLn8M

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RA.Xray.Hands

JAMA: Review of Adult Rheumatoid Arthritis

Jack Cush, MD

Smolen, Kerschbaumer, Aletaha, and Robinson have published a comprehensive review article of rheumatoid arthritis (RA) in JAMA, noting significant changes to our understanding and treatment guidelines.

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Leeds study of 44 patients idiopathic inflamm myopathy (IIM) pts Rx w/ rituximab showed a 70% response 4-6 mos post RTX. Responders had higher TIS (50·0 vs 17·5). Using highly sensitive flow cytometry, @ 2 wks responders had lower #s memory B cells & Plasmablasts. Is there a role https://t.co/HTxOIxkezs
Dr. John Cush @RheumNow( View Tweet )
EBR Journal Club: Dapirolizumab Pegol in SLE (PHOENYCS GO) The EBR Journal Club Companion applies my adapted version of the JAMA approach to critical appraisal to an important RCT in rheumatology. Each review covers four domains: Does this apply to my patients? What is the risk https://t.co/1jAvPfRI0m
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Swedish Pt Registry of 4317 AAV pts showed GPA & MPA had signif incr risk of CV dz (HR 2.04) & thromboembolism (HR 2.45); males incr MI risk (HR 2.25) & females incr ischemic stroke risk (HR 1.64). Sibs had no excess CVD-TE risk. The highest CVD-TE risk occurred within 3 mos. of https://t.co/FdbIXoCZf0
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Novartis & BMS CAR-T Cell Trials on Hold Reuters and the Wall Street Journal report that both Novartis and Bristol Myers Squibb (BMS) have paused their autoimmune disease CAR-T cell trials due to safety concerns, including deaths. https://t.co/ffcAHhtdBh https://t.co/zKlFcBdEod

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Chinese retrospective study of 140 Bx proven Kikuchi-Fujimoto pts shows very few evolve into #SLE. While 60% were ANA+ (11.3% other autoAbs) - none developed SLE (median F/U 39mos). KFD is benign, self limiting necrotizing lymphadenitis usually in young women. https://t.co/NjNoMOgNcC
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Necrotizing arteritis is rare w/ IgA Vasculitis (IgAV). Review compared 30 IgAV-NA to 257 adult IgAV & 196 PAN pts. Overall IgAV-NA is a severe IgAV phenotype with life-threatening complications & should prompt vascular imaging and intensified immunosuppression. IgAV-NA had more https://t.co/GRVcqRPKTL
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Metanalysis looked at neutrophil to Lymph ration (NLR) in SLE - 31 studies, 4,006 SLE pts. NLR signif incr in SLE worldwide. NLR was higher in Active vs inactive SLE, and showed a significant but moderate correlation w/ SLEDAI (CC=0.354, p < 0.001). https://t.co/tA6UBb1wVo https://t.co/XoXrf6HlKL

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Small series of 5 Idiopathic inflammatory myopathy (IIM) pts Rx w/ obinutuzumab for refractory myositis (2 antisynthetase syndr, 1 DM, 2 overlap myositis). 4/5 patients achieved complete response. Lung improved/stabilized in ILD patients. Two required second obinutuzumab cycle. https://t.co/ev9qlEO04l
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Ro52 Abs in idiopathic inflammatory myopathies (IIM). From 2,126 IIM China/Japan pts, Ro52 positivity was common (46%), esp in MDA5+ DM & anti-synthetase syndr (ASyS) & was assoc w/ high freq of ILD, rapidly progressive ILD, and poor prognosis. https://t.co/TA4gSnZax1 https://t.co/riYs5YJwQV

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Dr. John Cush @RheumNow( View Tweet )
EBR Journal Club: Dapirolizumab Pegol in SLE (PHOENYCS GO) The EBR Journal Club Companion applies my adapted JAMA approach to critical appraisal to an important rheumatology RCT. Each review covers four domains: Does this apply to my patients? What is the risk of bias? How https://t.co/kereLii5J6
Dr. John Cush @RheumNow( View Tweet )
Korean retrospective study compared NIDDM pts Rx w/ SGLT2 inhibitor (n 552,065) vs sulfonylurea (1,480,092) showed SGLT2 inhibitors were assoc w/ a signif 11% lower risk of incident autoimmune rheumatic disease (HR 0.89). Diff of −6.50 per 100K PYs over median ~9 mos F/U. https://t.co/uTiCjejkjL
Dr. John Cush @RheumNow( View Tweet )
Chinese retrospective study of 140 Bx proven Kikuchi-Fujimoto pts shows very few evolve into #SLE. While 60% were ANA+ (11.3% other autoAbs) - none developed SLE (median F/U 39mos). KFD is benign, self limiting necrotizing lymphadenitis usually in young women. https://t.co/Ai7W9GCBVb
Dr. John Cush @RheumNow( View Tweet )
Necrotizing arteritis is rare w/ IgA Vasculitis (IgAV). Review compared 30 IgAV-NA to 257 adult IgAV & 196 PAN pts. Overall IgAV-NA is a severe IgAV phenotype with life-threatening complications & should prompt vascular imaging and intensified immunosuppression. IgAV-NA had more https://t.co/XdPbGX770D
Dr. John Cush @RheumNow( View Tweet )
Metanalysis looked at neutrophil to Lymph ration (NLR) in SLE - 31 studies, 4,006 SLE pts. NLR signif incr in SLE worldwide. NLR was higher in Active vs inactive SLE, and showed a significant but moderate correlation w/ SLEDAI (CC=0.354, p < 0.001). https://t.co/ROG5L4nfo2 https://t.co/9mqqId45lG

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Dr. John Cush @RheumNow( View Tweet )
CART.Safety

Novartis & BMS CAR-T Cell Trials on Hold

Jack Cush, MD

Reuters and the Wall Street Journal report that both Novartis and Bristol Myers Squibb (BMS) have paused their autoimmune disease CAR-

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Small series of 5 Idiopathic inflammatory myopathy (IIM) pts Rx w/ obinutuzumab for refractory myositis (2 antisynthetase syndr, 1 DM, 2 overlap myositis). 4/5 patients achieved complete response. Lung improved/stabilized in ILD patients. Two required second obinutuzumab cycle. https://t.co/0uW6xXQQ2S
Dr. John Cush @RheumNow( View Tweet )
Insights into Sjögren’s Disease - A Rheum Survey In August 2026, RheumNow surveyed rheumatologists about Sjogren’s disease (SjD) - how they approach diagnosis, treatment, and unique challenges; all important as new advances in SjD evolves. https://t.co/kCfCNl3xnW https://t.co/rhj3UL4JuM

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Dr. John Cush @RheumNow( View Tweet )
FDA%20approved2.jpg

FDA Approves Brepocitinib to Treat Dermatomyositis

Jack Cush, MD

The FDA and Priovant recently annouced approval of brepocitinib (Lisraya), a JAK1/TYK2 inhibitor, for the indication of adults with dermatomyositis (DM). This is the first oral (once daily) agent approved for DM.

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JAK inhibitors work & have a dose dependent effect in severe alopecia areata (AA). Metanalysis of 10 Rxs, 3866 AA pts (used the SALT20 endpoint) showed the best efficacy was deuruxolitinib_12 mg, and baricitinib_4 mg (OR: 2.59, 95% CI: 1.98–3.38). https://t.co/k86f2RvCEJ https://t.co/N1fsrbbmDw

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Dr. John Cush @RheumNow( View Tweet )
Phase 1/2 COMPARE trial of CD19 CAR-T Rx in 6 ACPA+ RA pts w/ severe refractory Dz; after lymphodepletion, given mivocabtagene autoleucel (miv-cel), followed < 52wks. All had CRS, No ICANSs or serious AEs. All had CD19 cell depletion & Decr in AutoAbs. Efficacy: 3/6 had ACR70 & https://t.co/28dWMGWbKB
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Recent Blogs

rheumthought

CNS Lupus (NPSLE)

Jack Cush, MD
Cush RhTh CNS
29 yr. old woman with SLE and transverse myelitis. Is this NPSLE; how to diagnose?
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Unpopular opinion: spinach can be bad for you

Lara El Khoury, MD
pro con unsure opinion thumbs debate
PMR might be one of the most rewarding diagnoses to make in real practice: the patient comes to you in severe debilitating pain, and you prescribe steroids, giving them their lives back! As much as this impressive response makes your intervention appear almost magical, there is the often-forgotten story about the implications of such a diagnosis and treatment on patients' daily lives. 
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What Goes Wrong with the Immune System in PMR?

Kornelis van der Geest, MD, PhD
PMR,pathogenesis.JIM2022
Polymyalgia rheumatica (PMR) is a common inflammatory rheumatic disease. The exact trigger for PMR onset remains unknown. However, immunology studies and clinical trials with biological DMARDs now shed light on the immune pathways involved in PMR.
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