Weak Data (1.24.2025)
Dr. Jack Cush reviews the news and journal reports from RheumNow.com, and features Dr. Charity Dean, the Keynote speaker at RheumNow Live 2025, and why she is an inspiration.
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SLE subphenotypes predisposed by distinct genetic risk loci. Multicenter 10 yr genotyping study on 1462 SLE pts (56% w/ lupus nephritis & 43% not LN) found significantly higher polygenic risk scores (PRS); significant LN variants included HLA, TNFAIP3, BLK, & STAT4.… https://t.co/zvYGct9aqG https://t.co/obgkHbXNWA
Dr. John Cush @RheumNow( View Tweet )
ICYMI: Sex related differences in PsA
Different factors are known to influence disease characteristics and outcomes in psoriatic arthritis (PsA). Recently, there is new evidence that sex-related differences play a role not only in disease manifestations but also in efficacy and… https://t.co/60vdbWLltB https://t.co/nY1CuJhKMb
Dr. John Cush @RheumNow( View Tweet )
#CRISPR reviewed in
👇
#fibroblasts
Found deletion of certain genes
Ex JIA had marked change in expression
Yr in Preview ACR24 @RheumNow @ACRheum
Dr Chris Ritchlin 👏 https://t.co/jnmtk1eXGp
Janet Pope @Janetbirdope( View Tweet )
Severe thrombocytopenia (TP) is rare but linked to major organ involvement and poor prognosis in #SLE. Data from the RISE registry shows TP in 9.3% of SLE patients, with higher prevalence in males, African-Americans+ those with multiple comorbidities.
#ACR24 @RheumNow abst#2680
Bella Mehta @bella_mehta( View Tweet )
#Scleroderma #molecular #signatures in #skin predict long term outcomes
👇worst with inflammatory signature
This may have clinical and trial applicability
Nice work!
Abst0711 #ACR24 @RheumNow @ACRheum https://t.co/3CFxu6bACu
Janet Pope @Janetbirdope( View Tweet )
Study on #SLE and ESRD using machine learning:
Developed model to identify patients with SLE and ESRD
Used NIH 'All of Us' dataset
XGBoost outperformed Random Forest
SDOH data improved model precision #ACR24 @rheumnow #MachineLearning abst#1876 https://t.co/PQ7u4Pj5OH
Bella Mehta @bella_mehta( View Tweet )
Abstract 1873: The impact of urbanization on lupus nephritis mortality is complex.
Race/ethnicity + income modify the effects
- Income ≥$50k + living in suburbs associated with lower odds of mortality due to LN in racial/ethnic minorities
@RheumNow #ACR24
Akhil Sood MD @AkhilSoodMD( View Tweet )
Why is there female predominance in #SLE - the extra X chromosome in females (XX) may not be inactivated properly- usually maintained by the long non-coding RNA #Xist
#ACR24 abst#2599 @RheumNow https://t.co/C9Qj5zSnpN
Bella Mehta @bella_mehta( View Tweet )
Abstract 1876: Developed a machine learning model w/ #SDoH covariates to accurately identify patients with SLE and ESRD in NIH All of US dataset
@RheumNow #ACR24 https://t.co/TLDSiBZZPs
Akhil Sood MD @AkhilSoodMD( View Tweet )
A#2528
Hes1/Piezo1 Pathway - role in osteocyte response to mechanical stimulus
Yoda1 - Piezo1 agonist shown to help fx healing in mice
Piezo1 decrease in GIOP
Basic sci research shows activation of pathway promotes mechanical stress response, decr GIOP
#ACR24 @RheumNow
Eric Dein @ericdeinmd( View Tweet )
A#2530
ANA reactive CD4 cells: elevated B cell help activation in SjD
Unique autoreactive T cell cluster in SSc shows CD4+ TRAIL+ IFN type I - unique to SSc
Leads to decrease activation of APCs, decrease CD4 T effector fxn
@RheumNow #ACR24 https://t.co/4JnA3SpVM8
Eric Dein @ericdeinmd( View Tweet )
Now we have GWAS, we are getting polygenic risk scores for RA, and we can see what disease risks cluster with RA risk.
RA genetic risk clusters with risk for:
type 1 diabetes
thyroiditis
multiple sclerosis
What draws these diseases together?
#ACR24 ABST1365 @RheumNow https://t.co/28gU1nBEUG
David Liew @drdavidliew( View Tweet )
#1689: race-neutral 🫁 function equations in SSc improve equity:
🔹 Race-specific equations underestimate disease severity in Black patients.
🔹 Switching to race-neutral reclassified 45% of Black patients to more severe, 16% of White patients to less severe
@RheumNow #acr24 https://t.co/BfK2PsCMX5
Caoilfhionn Connolly @CaoilfhionnMD( View Tweet )
#2282
🔬 Personalised Approach to TNFi in RA
📊 N=50👇; 43 responders
🔑 Findings
💥TNFR2 rs1061622 polymorphism linked to TNFi response
💥 MR/RR alleles ⬆️ 10X odds non-response v. MM allele (OR = 10.1,p=0.04)
🎯Genotyping may guide personalized RA therapy.
#ACR24 @RheumNow https://t.co/MQKZUCEPxj
Caoilfhionn Connolly @CaoilfhionnMD( View Tweet )
Navigating Positive ANA: Leveraging AI for better triage
Abstract 1526: Markus et al. developed a machine learning model to predict progression to SLE, utilizing diagnoses, meds, procedures, and labs collected 2 years before and 5 years after +ANA.
@RheumNow #ACR24 https://t.co/2zzSH8Pb0e
Links:
Akhil Sood MD @AkhilSoodMD( View Tweet )
What is my risk of developing SLE?
Abstract 0843 highlights a predictive model that accurately classifies SLE risk using genetics, lifestyle, and environmental factors. Model 3 (genetics + environment + lifestyle) performed the best compared to models 1 and 2.
@RheumNow #ACR24 https://t.co/sk9oG0OY3W
Akhil Sood MD @AkhilSoodMD( View Tweet )
#0066
🧬Epigenetics, Gut Microbiota & RA
🔬 110 RA patients v 110 controls
🦠 Collinsella abundance a/w DNA methylation changes (PRHOXNB, TBC1D22A) in RA, correlating with disease activity.
💡❔Role of gut microbiota & epigenetic markers as RA biomarkers
#ACR24 @RheumNow https://t.co/yZn0KkRpE6
Caoilfhionn Connolly @CaoilfhionnMD( View Tweet )
Abstr#0647
Toronto Lupus Clinic finds pericarditis in 20% of #SLE inception cohort, often with skin, heme, MSK, & renal involvement. Linked to younger age, White race, +SSB, & lower ACR/EULAR scores
- Tx: GC, HCQ, AZA
@RheumNow #ACR24
Akhil Sood MD @AkhilSoodMD( View Tweet )
A study in difficult-to-treat (D2T) ankylosing spondylitis (AS) reveals distinct characteristics in patients, including: - Higher BMI - Increased comorbidities - Presence of EAMs - HLA-B27 positivity is linked to higher odds of being D2T, highlighting potential genetic… https://t.co/XcShdxSwhm
Antoni Chan MD (Prof) @synovialjoints( View Tweet )
Hypophosphatasia:
🦴Inherited disorder of metabolism with low tissue nonspecific alkaline phosphatase (TNSALP)
🦴Impaired bone mineralisation
🦴Accumulation of pyrophosphate
🦴1/100,000-300,000
🦴6 main forms
@RheumNow #ACR24
Mrinalini Dey @DrMiniDey( View Tweet )
#ACR24 Ab#0771
ARID5B - transcription factor controls pathologic inflammatory fibroblast
ARID5B: RA risk locus on GWAS, also link to SLE, Graves
Binds to histone editors to epigenetically regulate fibroblast state
ARID5B deletion incr inflamm response, overexpr decr
@RheumNow https://t.co/ebKnX1uTuO
Links:
Eric Dein @ericdeinmd( View Tweet )
Role of X chromosome in autoimmune disease?
SLE increased in Klinefelter (XXY), decreased in Turner’s (XO)
X chromosome inactivation with Xist
Inductively transgenic expression of Xist in male mice induces autoantibodies
Year in Review #ACR24 Bridges
@RheumNow https://t.co/M88f0v0kpe
Links:
Eric Dein @ericdeinmd( View Tweet )
A Polygenic Model for Still's Disease
Adult-onset Still's disease (AOSD) is systemic autoinflammatory disorder of unknown etiology. It is considered among the febrile autoinflammatory etiologies. Now a cohort study shows that AOSD patients may be enriched in germline variants usually limited
Late-onset axSpA (LOS) is more likely to have peripheral arthritis. but less HLA-B27 & +FHx of AS/SpA. Portugese study of 2165 axSpA pts. 273 LOS (Sx onset >45 yrs; mean 51yrs; 55% men) had less B27 (51% vs 65%), +FHx (8% vs 14%), inflam LBP (81% vs 88%), Uveitis (13% vs 20%)… https://t.co/DgRUt1ejxT https://t.co/dGX2bfKhnK
Dr. John Cush @RheumNow( View Tweet )
Recent Blogs
Cush and Dao are at it again. This time it's whether men or women are better patients. Cush says men are better patients; Dao says Er, not so fast bub! This is their light-hearted, gender biased debate on the best patients: Men vs. Women.
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