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A Polygenic Model for Still's Disease

Jack Cush, MD

Adult-onset Still's disease (AOSD) is systemic autoinflammatory disorder of unknown etiology.  It is considered among the febrile autoinflammatory etiologies.

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Genes Linking Rheumatoid Arthritis and Osteoporosis

EurekAlert!

Rheumatoid arthritis is a common disease affecting an estimated 17 million people worldwide. The disease is caused by immune cells attacking the joints and can result in pain, swelling, and damage to the cartilage and bone.

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All in the Family (8.23.2024)

Jack Cush, MD

Dr. Jack Cush picks highlight reports from the past week on RheumNow.com, with reports on the challenge of lupus nephritis, perplexing skin issues, you don't know JAK (about Tyk) and the value of a good family history.

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pedigree.genetics.family.history

A Family History of Arthritis?

Jack Cush, MD

Using data from the population based All of Us (AoU) Research Program, a self reported history of arthritis and related conditions was associated with an increased risk for arthritis, osteoporosis, and carpal tunnel syndrome.

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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

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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

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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

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Eric Dein ericdeinmd ( View Tweet)
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)
Gut microbiome changes linked to onset of RA Changes in the make-up of the gut microbiome are linked to the onset of clinically evident rheumatoid arthritis in those at risk of the disease because of genetic, environmental, or immunological factors, suggests research published… https://t.co/gUgYLOKrI0 https://t.co/d75NmKup2U
Dr. John Cush RheumNow ( View Tweet)
171 SSc pts w/ hand Xrays and US found 20% w/ Joint involvement. Active Synovitis & tenosynovitis predicted by CRP>10mg/L (p = 0.013), fibrotic tenosynovitis on US (p = 0.005), anti-RNA polymerase III antibodies (p = 0.043) https://t.co/OIornA9sAA https://t.co/yXyX5k2yqD

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Dr. John Cush RheumNow ( View Tweet)
Scleroderma registry enrolled SSc pts w/o ILD. Incident ILD occurred in 199/969 (21%) pts over median 2.4yrs. Late onset SSc-ILD (>7yr from Raynauds) occurs 32% less. These pts were more White, w/ arthritis & RNA-polymerase III Abs, but have similar ILD Progression (vs… https://t.co/zdL4OPEPhi https://t.co/wl9XmsCHIE
Dr. John Cush RheumNow ( View Tweet)
Systematic review suggests (although not provn) that audiovestibular dysfunction may be from APS. Anti-phospholipid & HSP-70 Abs found 25-33% w/idiopathic sudden sensorineural hearing loss,. ACL Abs seen in up to 27% w/ sensorineural hearing loss https://t.co/GTcLoM0SCZ https://t.co/afFntYnPPG

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Dr. John Cush RheumNow ( View Tweet)
Heritability of asymptomatic ANA positivity is 25%. Asymptomatic ANA positive individuals did not exhibit increased cumulative genetic risk for lupus compared to ANA negative individuals. Genetic study of 1,955 asymptomatic ANA+ v 3,634 asymptomatic ANAnegs.… https://t.co/P0MmFfG7NV https://t.co/KnlyNPKG4s
Dr. John Cush RheumNow ( View Tweet)
GWAS study of 2.6 million people (120,295 w/ prevalent gout) detected 377 loci & 410 independent genes (149 prev unreported), includes genes of inflammation, epigenetic remodeling, cell osmolarity, NLRP3 activity, & clonal hematopoiesis (CHIP) https://t.co/GmXWtTlJkO https://t.co/xPK2Iy3NRj

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Dr. John Cush RheumNow ( View Tweet)
JCI article on Mechanisms underlying sex differences in autoimmunity - factors include sex hormones, X chromosome genes, sex-specific epigenetic effects of estrogen & environment, and microRNA effects. Also mitochondria & autoantibodies discussed https://t.co/hTrizE8jFK https://t.co/VixAZsYBzb

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Dr. John Cush RheumNow ( View Tweet)
Full read review of Neonatal lupus syndrome - caused by pathogenic maternal autoAbs (SSA, SSB) in fetal circulation. Mild Sxs in 25%, severe Sxs are rare; Heart block in up to 2% of neonates born to mothers with positive antibodies. https://t.co/iH4MBRGvg1 https://t.co/kXxIeQC47m

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Dr. John Cush RheumNow ( View Tweet)
Metanalysis of Social determinants of health and lupus nephritis (31 studies) showed poor LN outcomes were 1.47-fold higher w/ any adverse SDoH. Also multiplicative impact of having two or more adverse SDoH on LN outcomes. https://t.co/4oEuAEgBx1 https://t.co/OkeRzrCXzQ

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Dr. John Cush RheumNow ( View Tweet)
All in the Family (8.23.2024) Dr. Jack Cush picks highlight reports from the past week on RheumNow, with reports on the challenge of lupus nephritis, perplexing skin issues, you don't know JAK (about Tyk) and the value of a good family history. https://t.co/gwM77mJCnr https://t.co/HOGnymjhSZ

Links:

Dr. John Cush RheumNow ( View Tweet)
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