Megan Cooper

In the 5 years since we first reported TLR8 GOF we have learned -it is X-linked DOMINANT -mosaic or germline variants with AA 432, an antagonist binding site, most commonly affected -patients can be very sick, early recognition by deep sequencing and get them to HCT -emerging spectrum of severity

Hematopoietic cell transplantation using treosulfan-based conditioning for IL-10 receptor deficiency. New report by Madhavi Lakkaraja @fredhutch.org, Erica G. Schmitt @washumedicine.bsky.social et al.: rupress.org/jhi/article/... @macattacklab.bsky.social #cytokines #InbornErrorsOfImmunity #HSCT

In @jhumimmunity.org, @macattacklab.bsky.social review the molecular, immunologic & clinical features of #TLR8 gain-of-function syndrome. They review findings from patients w/ mosaic & germline disease & integrate knowledge of key structural components of the TLR8 protein rupress.org/jhi/article/...

McTaggart, Lim, Amarnath, Carpenter, Laurence et al. report on a #CTLA4 homozygous variant identified in a 16-year-old male. CTLA4 expression was severely diminished in CD4+ T cells and T regulatory cells. rupress.org/jhi/article/... #homozygous #PID #checkpoints #Tregs #InbornErrorsOfImmunity

JAK-inhibitor treatment induces rapid yet incomplete immune reconstitution in #STAT1 gain-of-function. New study from Cecilia Iglesias-Herrero, Rik Schrijvers (KU Leuven) and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity

IRF4 p.T95R combined #immunodeficiency: Clinical features and transplant outcomes. New study from Mattison P. Stojcic, Stuart E. Turvey (@turveylab.bsky.social, BC Children's Hospital, Vancouver) and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity #ClinicalPhenotypes #HSCT

Galli, Recher et al. @unibas.ch describe two patients with hypogammaglobulinemia associated with #MyotonicDystrophy type 1 (DM1), a rare and underdiagnosed monogenic neuromuscular disorder and provide clues to aid clinical immunologists in making a correct diagnosis. rupress.org/jhi/article/...

#HowITreat from Joseph Oved: In primary immune regulatory diseases and inflammatory disorders, targeted immune modulation may control symptoms for some, but alloHCT remains the only cure for many patients. rupress.org/jhi/article/... #Infections #autoantibodies

Sbruzzi, Vianna et al. show that neutralizing #autoantibodies against type I IFNs are more frequent in severe, critical, and fatal #COVID19 cases in southern Brazil, highlighting their role in disease severity and extending global evidence to a Latin American population. rupress.org/jhi/article/...

In this month's issue of Arthritis Care & Research, we present a collection of special articles celebrating 50 years of pediatric rheumatology and the advancements in care that have been achieved. Read the October issue: acrjournals.onlinelibrary.wiley.com/toc/21514658...

A pleasure to work with Ofer Zimmerman & @washumedicine.bsky.social heme to make the diagnosis in this adult woman who had symptoms for two decades. TLR8 GOF is X linked DOMINANT -males & females. Our original cohorts were younger (I’m a pediatrician!) there are more older adults out there

Dr. Daniel Kastner, former NHGRI Scientific Director, was a visionary physician-scientist whose discoveries transformed the understanding of innate immunity and established the modern field of autoinflammatory diseases. Gupta, Goldbach-Mansk & Aksentijevich pay tribute: rupress.org/jhi/article/...

We all know recurrent infections is a hallmark of many primary immunodeficiencies, but what really is "recurrent"? In the electronic health record, recurrence is far from obvious. Aaron figured out a way to tease recurrence from the data. The impact is finding immune deficiency patients sooner. #IEI

#Exome sequencing can stratify the genetic risk of #CeliacDisease among first-degree relatives of affected individuals. A study from Talha Asif, Xiao-Fei Kong et al. (UT Southwestern) finds that about 10% of first-degree relatives carry a particularly high genetic risk. rupress.org/jhi/article/...

@pauljbaker.bsky.social, @sethlucianmasters.bsky.social et al. identify a 13-year-old male with complex symptoms including those consistent with familial chilblain lupus. This inborn error of immunity is due to a genomic translocation resulting in SAMHD1 deficiency rupress.org/jhi/article/...

Adenosine deaminase type 2 deficiency: from rare to common. New review from Marjon Wouters, Ivona Aksentijevich, Isabelle Meyts @isabellemeyts.bsky.social (KU Leuven) and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity #Autoinflammation

TCR γδ cell–specific STAT5 gain of function induces a druggable chronic human immune dysregulation. New study from Benedikt J. Meyer, José Pedro Loureiro, Mike Recher and colleagues @biomedizin.unibas.ch @unibas.ch: rupress.org/jhi/article/... #IEIs #InbornErrorsOfImmunity

Giardino et al report the first detailed immunological characterization of a DEGCAGS patient, showing that biallelic ZNF699 loss-of-function variants can cause syndromic combined #immunodeficiency & DNA methylation profiling improves diagnostic precision in selected #IEIs rupress.org/jhi/article/...

In a new review on DADA2, @isabellemeyts.bsky.social et al. cover the full spectrum of disease (#vasculitis, bone marrow failure, #immunodeficiency), TNF inhibitors, stem cell transplant, & #genetherapy on the horizon, the concept that a single variant can cause disease. rupress.org/jhi/article/...

How I Treat: Diagnostic clues and treatment for activated phosphoinositide 3-kinase delta syndrome. Hirokazu Kanegane @sciencetokyo_en, Dan Tomomasa, and Satoshi Okada propose “10 Warning Signs of APDS” for the early clinical detection of APDS: rupress.org/jhi/article/... #HowITreat #IEIs

OSMR study published! By identifying biallelic OSMR deficiency as a novel Primary Atopic Disorder, we uncover a previously unrecognized mechanism driving severe allergic disease and provide new insights into the biology of human atopy. Congratulations to an outstanding team of collaborators.

C5 inhibition restores B cell homeostasis and humoral immunity in #CHAPLE disease patients. New study from Azzeddine Tahiat (Rouiba Hospital, Algeria), Dusan Bogunovic @bogunoviclab.bsky.social @columbiamed.bsky.social and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity

Human germline biallelic loss-of-function OSMR variants cause severe allergic disease. New study from Simran Samra, Mehul Sharma, Stuart E. Turvey @turveylab.bsky.social and colleagues: rupress.org/jhi/article/... #Immunology #Genetics #Atopy #IEIs #InbornErrorsOfImmunity

How I Treat: #STAT3 hyper IgE syndrome. Clinical management guidelines proposed by Cliodhna Murray, Eyad Jannoud, Seraina Prader, and Bodo Grimbacher @uni-freiburg.de: rupress.org/jhi/article/... #HowITreat #InbornErrorsOfImmunity #IEIs

Really happy with this new paper just published in @jhumimmunity.org

How I Treat: Immune dysregulation in #DownSyndrome. Melissa Gans (University of Miami Miller School of Medicine) and colleagues propose actionable insights: rupress.org/jhi/article/... #HowITreat #Autoimmunity #InbornErrorsOfImmunity @bogunoviclab.bsky.social

Primary atopic disorders: Monogenic insights into immunity. Bhavi Modi, Stuart Turvey @turveylab.bsky.social et al. review how primary atopic disorders, a group of monogenic #InbornErrorsOfImmunity, reveal fundamental mechanisms regulating allergic #inflammation. rupress.org/jhi/article/... #Atopy

Functional characterization of Griscelli syndrome type 2 sine albinism in Japanese patients. New study from Tatsuhiko Tanaka, Akira Sugawara, Ko Kudo (Hirosaki University), Mitsunori Fukuda (Tohoku University) and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity

Who would have thought 30 yrs ago that there would be > 50 inborn errors of immunity underlying atopy ? This has been the most insightful study of allergy: Primary atopic disorders: Monogenic insights into immunity rupress.org/jhi/article/...

A warm welcome from NOLA for #CIS2026 meeting! @clinimmsoc.bsky.social

New, exciting insights onto the thymic biology and medicine of the 22q/DGS: Fibroblast-driven collagen expansion and altered thymic medullary niches in 22q11.2 deletion syndrome rupress.org/jhi/article/...

Looking forward to #CIS2026 @clinimmsoc.bsky.social in #NewOrleans in just 2 days - lots of great science to look forward to!

In a new study from Tan, Kergaravat, @petterbrodin.bsky.social et al., longitudinal profiling of 136 newborns shows thymic output peaks at 3–4 mo, correlating with plasma RANKL, lymphotoxin-α, and the TCRD variant rs2204985. rupress.org/jhi/article/...

HA20: an underrecognized #immunedysregulation disease affecting up to 1:14,000. Jonathan Li, Daniella M. Schwartz et al. cover diagnosis, #biomarker-guided therapy with IL-1/TNF/JAK inhibitors, and family screening: rupress.org/jhi/article/... #HowITreat #raredisease #autoinflammatory #IEI #PIRD

Hennings, Ekwall et al. integrated spatial transcriptomic and proteomic analyses of #thymus tissue from patients with 22q11.2 deletion syndrome to identify fibroblast-driven collagen expansion and alterations in medullary niches. rupress.org/jhi/article/... #InbornErrorsOfImmunity

Using clinical vignettes, Melissa Gans et al. highlight the underlying mechanisms and potential treatments for immune dysregulation in #DownSyndrome. rupress.org/jhi/article/... #HowITreat #Autoimmunity #InbornErrorsOfImmunity @bogunoviclab.bsky.social

Researchers led by Drs. Michael Gantier, Toshiyuki Shimizu, and Ben Corry show that modified #RNA from our own cells naturally blocks TLR7 and TLR8, preventing harmful immune activation. 📖: https://go.nature.com/4azVWjp 🔊: https://bit.ly/40muGA2

Human CD21ˡᵒT-bet⁺ B cells: Not as easy as "ABC"! New review from Stuart G. Tangye (Garvan Institute of Medical Research): rupress.org/jhi/article/... #InbornErrorsOfImmunity #Infections #AutoAntibodies

New hope for these patients: Expanding the scope of PI3K-δ inhibition: Leniolisib treatment in PRKCD deficiency rupress.org/jhi/article/...

Excellent expert consensus for treat CGD

New review from Stuart G. Tangye provides an overview of the discoveries, origins, and complexities of CD21ˡᵒ B cells, and how studying inborn errors of immunity can provide a unique window to understand the molecular requirements for generating these cells. rupress.org/jhi/article/...

A thoughtful consensus on how to manage patients with CGD: How I treat chronic granulomatous disease url: rupress.org/jhi/article/...

This is a thorough, critical, and superb Review of a complex and controversial human B cell subset, the famous "ABC" -- a must-read !👇 Human CD21loT-bet+ B cells: Not as easy as “ABC”! url: rupress.org/jhi/article/...

Does anyone have serum/plasma from a cohort of (ambulatory) patients with herpes zoster (shingles) ? A small cohort would be fine. We will test if they have auto-Abs against type I IFNs, as the risk of zoster increases over 50 yo. Please RT or contact me !

Refractory infantile #IPEX with Treg-restricted FOXP3null expression caused by a novel variant in #FOXP3. New study from Ahmad Rayes, Rosa Bacchetta and colleagues @uofuhealth.bsky.social: rupress.org/jhi/article/... #InbornErrorsOfImmunity #Autoimmunity @clinimmsoc.bsky.social

Familial lupus associated with a P2RY8 variant: navigating the boundary between monogenic disease and genetic susceptibility to #lupus. New report from Clémence David, Marie-Louise Frémond @institutimagine.bsky.social and colleagues: rupress.org/jhi/article/... @esidsociety.bsky.social