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Pathogenesis of Autoimmune Liver Disease
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EurekAlert!
Autoimmune liver diseases (ALDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), are complex conditions involving the liver's immune-mediated damage.
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Pollution and Autoimmunity (7.12.2024)
Dr. Jack Cush reviews the news and journal articles from the past week on RheumNow.com.
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PNAS & Nature Insights into Lupus Pathogenesis
Two prominent medical journals this week published new insights into the pathogenesis of systemic lupus erythematosus (SLE), with both inidicating promient roles for T cells in what is a classically viewed as a humoral (B cell) disorder.
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268/279 SLE pts w/ kidney biopsy for proteinuria were Dx w/ lupus nephritis. Proliferative LN (III/IV+V) had higher levels of C1q, chromatin, dsDNA, ribosomal P Abs. C1q & dsDNA independently assoc w/ proliferative LN. AutoAbs decreased in proliferative LN https://t.co/tRucgJRpDN https://t.co/DtgEmGhUzd
Dr. John Cush RheumNow ( View Tweet)
AbbVie has submitted regulatory applications to both the FDA and the European Medicines Agency for Rinvoq (upadacitinib) to treat adult patients with giant cell arteritis (GCA) https://t.co/LqRcm2FEFV https://t.co/XEjjSNnOGt
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Full read overview of myositis associated - ILD (and treatments), including:
- Case examples
- Antisynthetase Syndrome
- Anti-MDA5 Amyopathic DM
- Interstitial Lung Disease in Myositis https://t.co/zQpfstnGy8 https://t.co/XogyyxuVMk
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Preliminary results from RESET-RA Study announced; demonstrating ACR20 efficacy of implanted vagal nerve stimulation at 12 wks (p=0.0209). 2-staged, multicenter, randomized, sham-controlled, double-blind pivotal trial, enrolled 242 RA pts https://t.co/gIVJd9F6Pk https://t.co/SNjWIa3raB
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Study from the UK Biobank (n 459K) shows long-term exposure to air pollutants (PM2.5, PM10, NO2, and NOx) may increase the risk of #SLE. 399 SLE pts (F/U 11.8 yrs) found an 18027% incr SLE risk w/ pollutants; magnified in those with high genetic risk https://t.co/PI4rvKwfpj https://t.co/2CZ28rHVG2
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Efficacy of Biologics in Patients with CKD
A retrospective cohort study of biological bDMARDs persistence in RA patients w/CKD, shows the 3 year survival to be > 50% but all studied biologics were nearly equivalents with regard to safety and efficacy.
https://t.co/rL2ZondUsE https://t.co/1hM237Jl83
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In the US CorEvitas registry of 1823 PsA pts; 11.1% fulfilled fibromyalgia definition & 20.6% had widespread pain. FM was assoc w/ female, depression/anxiety, impaired function, increased BMI, comorbidities. cDAPSA, patient pain& TJC https://t.co/YwRBYo1aR6 https://t.co/TXraU0F3Mh
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FDA adverse event study of JAKi in #RA assoc w/ signif more VTE, ischemic heart Dz, & tachyarrhythmias. 75,407 on JAKi vs 303,278 on biologics (TNFi, RTX, TCZ); JAK had more VTE (ROR=2.11), CVA (ROR=1.25), IHD (1.23), arrhythmias (1.15 ), esp in 1st yr. https://t.co/IVsGwqpiJK https://t.co/4epOHdNHbO
Links:
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Sobi has submitted a biologics license application to FDA for SEL-212 (pegadricase a uricase enzyme that breaks down uric acid) based on DISSOLVE I & II RCTs. SEL-212 was given FDA FDA’s Fast Track designation in March 2024 https://t.co/TPcUnCJOxT https://t.co/X1DrFDJZeK
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Full read, comprehensive review of NLRP3 inflammasome & its role in inate immunity (eg, infections), but also lifestyle (obesity, diabetes, NAFLD, heart/lung disease, periodontitis) and autoimmune diseases https://t.co/rCk9ncEsGA https://t.co/qc9eSIAVYe
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European Research Council has awarded a Proof of Concept Grant to Institute of Bioengineering of Catalonia and their OrthoBots project, to study the treatment of joint diseases using nanorobots to deliver nanoparticle based therapy to synovial tissues https://t.co/JmYQ1727rf https://t.co/k5uZoSwJPo
Dr. John Cush RheumNow ( View Tweet)
ICYMI: Community-Acquired Pneumonia (CAP)
https://t.co/geb8y2AK26 https://t.co/cB3y5vQoz1
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Progress in SLE with new mRNA CAR-T cell Trial
Cartesian Therapeutics, has announced their first-in-class mRNA CAR-T therapy has been given to the first SLE. patient in a Phase 2 open-label clinical trial.
https://t.co/7SYNtjIn9F https://t.co/a5LJn8QLT3
Dr. John Cush RheumNow ( View Tweet)
Urticarial vasculitis - rare autoimmune dz w/ persistent edematous papules & plaques lasting >24 hrs, w/ systemic Sxs (joint pain, fever). Long-lasting skin lesions tend to leave a bruiselike look. Requires Bx show leukocytoclasticl vasculitis https://t.co/cFWrntrlMw https://t.co/JPkh5FVNo3
Links:
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ICYMI: 2022 EULAR Recommendations on Screening & Prophylaxis for Opportunistic Infections
https://t.co/eHn2o2pFFR https://t.co/8S1fzl4AaJ
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MTX was tapered or D/C in 30% of RA pts w/in 2 yrs of b/tsDMARD Rx. Of 889 pts, MTX (19 mg/wk) tapered in 13.8% & D/C 16.5% (planned taper(37%); pt decision (27.2%). In 582 (66%) MTX unchanged, 4.25 increased MTX after b/tsDMARD initiation https://t.co/yc8exMbeD1 https://t.co/b3L3Fha7xU
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Bimekizumab (dual-IL-17A/F inhib), may prevent uveitis in patients with axSpA. In phase 3 RCTs (MOBILE 1 & 2) double-blind period, uveitis seen in 0.6% on BKZ vs 4.6% on PBO (p=0.001). In pts w/ hx uveitis, again lower w/ BKZ (6.2/100 PYs vs 70.4/100 PYs) https://t.co/v0wMK45chz https://t.co/CVPdg1k41V
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