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S.Korean study of 481 pts w/ myositis (IIM) - 12.9% (n = 62) had myositis-assoc. cancer. CA risk factos= older age, male, current smoking, dermatomyositis, TIF1γ; but lower risk w/ anti-synthetase synd, overlap myositis, arthritis, & ILD. SCRIM score had AUROC = 0.852 https://t.co/MdU1fRWWgS
Dr. John Cush RheumNow ( View Tweet)
Rheumatoid arthritis and the ‘big bang’ at #ACR25!
Is there ‘bang for the buck’ using big data to help predict who will develop RA in at-risk populations and similarly to predict response to csDMARDs, TNFi and JAKi in RA?
https://t.co/QDvdiP3q9R https://t.co/cz4j4vZkSd
Dr. John Cush RheumNow ( View Tweet)
Needle in a haystack
What T cell to target for #autoimmune diseases
T cell repetoires (TCR) not all are sequenced and many can exist to present antigens
Diff scales of approaches
Implications CAR-T
CD19
CD20
BCMA
Treg
HLAB27
etc!
#ACR25 @ACRheum @RheumNow
Alok Joglekar
#26S08 https://t.co/Qgw8Akz1xk
Links:
Janet Pope Janetbirdope ( View Tweet)
Will #PAD4 levels predict pts w #CCP positive #arthralgia who will develop #RA?
Leeds study - 79 at risk pts
PAD4 levels may predicting #rheumatoid #arthritis development
#ACR25 @RheumNow @ACRheum abst#832 https://t.co/dnAA6z3NJQ
Janet Pope Janetbirdope ( View Tweet)
#ACR25 Abstr#LB21 Are they novel somatic variants beyond #VEXAS in driving inflammation in undiagnosed SAID?Unbiased enrichment analysis in 265 UBA1-negative adults identified IDH1/2 hotspot mutations. Cd be used to screen esp those with cytopenia. Sorry pix not allowed @RheumNow
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
A deep dive into Lupus 🔬
Abstract 2601: Single-cell insights in SLE & pre-clinical autoimmunity
🔹 Plasmablast expansion → high disease activity & SLE risk
🔹 Metabolic activity varies by cell type
🔹 Established disease: ↑ glycolysis & OxPHOS changes
@RheumNow #ACR25
Akhil Sood MD, MS AkhilSoodMD ( View Tweet)
#ACR25 Abstr#2601 At single cell level using CyTOF, metabolic activity varied btw HC & autoimmune groups but clusters in At-Risk ANA+ve appeared closer to #SLE. ANA+ve who progressed to AI-CTD showed Plasmablast expansion & enhanced glycolysis. Could be used as target @RheumNow https://t.co/jtrM1wvQLk
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
A new genetic score for ILD prediction! 🫁
Developed in the Veterans RA cohort and Validation in a Swedish cohort
Model using classic RA-ILD risk factors and a cocktail of genetic risk
A cut off of 0.05 in this cohort would exclude 36% from HRCT or PFTs
Good performance https://t.co/6UsoSQAtyK
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
#1723 Why is systemic autoimmunity more common in females?
Loss of X-chromosome inactivation maintenance in B cells (not T cells) amplifies interferon-driven disease, with increased autoantibodies, inflammation and renal injury. Key mechanistic advance. @RheumNow #ACR25
Mrinalini Dey DrMiniDey ( View Tweet)
#ACR25 SMILE RCT of Incomplete #SLE (ANA+ but not meeting SLICC) showed HCQ didn’t slow down SLE progression. But multiplex arrays showed reduction in autoantibodies with HCQ that were distinct from abs assoc. w progression. Would biomarker endpoints be the answer? @RheumNow https://t.co/XcvacgObVo
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
Short chain fatty acids (SCFA) and the relevant microbiome have been linked to RA development and severity.
Study of monozygotic twins, where only one has RA, two diff cohorts:
lower SCFA
lower SCFA microbiome
Biomarkers, or even therapeutic target?
#ACR25 ABST0442 @RheumNow https://t.co/HW1YfkfOG3
David Liew drdavidliew ( View Tweet)
#0794 LLMs can accelerate qualitative lupus pregnancy research. Using AI to translate & analyze interviews from Portuguese, GPT-4 achieved top accuracy & coherence vs human themes. LLMs may expand inclusion & equity in rheum research. @RheumNow #ACR25 https://t.co/TAxg6Qyk0L
Mrinalini Dey DrMiniDey ( View Tweet)
Fascinating: tDR-1, a microbial sRNA, appears protective for RA in at risk ACPA+ pts:
- tDR-1 higher = less develop RA
- can predict seropos RA development
- in vitro type 1 IFN mapping checks out
Useful in itself, but importantly: why does it happen?
#ACR25 ABST0775 @RheumNow https://t.co/ep99dNAzFV
Links:
David Liew drdavidliew ( View Tweet)
tRNA-derived RNA (tDR-1), circulating microbial RNA
Associated w/ reduction in risk of RA conversion in asymptomatic CCP+ individuals (60 vs. 120+ ctrls),
‼️ tDR-1 alone over performs prediction model w/ smoking shared episode and RF w/ AUC 0.86
What is the mechanism? tDR-1 https://t.co/fuyk4NeOyA
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
What can we learn from longitudinal peripheral blood multi-omic profiling in at-risk individuals?
50 RA converters vs. non converters from StopRA study
Decision tree showing highest risk for conversion to clinical RA in Individuals w/
-CCP3 ≥108 units
-T peripheral helpers https://t.co/jw53EB6tI6
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
#0774
Multi-omic profiling of anti-CCP3+ “at-risk” individuals reveals Tph & cytotoxic CD8+ expansions, altered gene/chromatin profiles and predictive model (AUC 0.77) for RA conversion
PTPN22 locus accessibility & Tph ≥ 2.45% identify highest risk. @RheumNow #ACR25 https://t.co/JDSMkdmoGv
Mrinalini Dey DrMiniDey ( View Tweet)
A new marker for stratification of ILD in dermatomyositis: Anti MDA5 antibodies!
Japanese study
MDA5 (201-300) positivity associated w/
Lower 6-month progression-free survival (43% vs. 74%)
Lower 5-year survival rates (34% vs. 66%)
Validation in other populations awaited https://t.co/IBiYyATer4
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
Clinical and Genetic Effects of Neuropsychiatric Lupus
The clinical features and genetic abnormalities of neuropsychiatric systemic lupus erythematosus shows that NPSLE often means more severe lupus and more organ involvement beyond the central nervous system. https://t.co/7Ujo6Kaf1N
Dr. John Cush RheumNow ( View Tweet)
Sequencing DNA to find new lupus treatments
MUSC geneticist Betty Tsao, Ph.D., will lead a five-year project to identify rare mutations associated with childhood-onset SLE, or lupus, with more than $3.5 million in funding from the National Institute of Arthritis and https://t.co/1vfQ4fK6FX
Dr. John Cush RheumNow ( View Tweet)
HLA-B27: still the most important genetic factor in axSpA susceptibility, but has lower frequency African American, South American & Middle Eastern pop. B27 discerns clinical subsets of SpA and PsA, particularly acute anterior uveitis or axSpA with psoriasis, https://t.co/S4s0NvuwNY
Dr. John Cush RheumNow ( View Tweet)
