The important things about this great case report are 1) that we often think about mycobacterial susceptibility with *loss* of STAT1 signaling (eg MSMD) but this one is gain of function. And 2) no thrush. #IEI

Journal of Human Immunity@jhumimmunity.org · last mo.

#STAT1 gain-of-function variant in a previously healthy patient with disseminated Mycobacterium genavense infection. New study from Kavitha Thiagarajan, Huan Vinh Dong, Karin Nielsen-Saines (University of California, Los Angeles) and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity

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

Journal of Human Immunity@jhumimmunity.org · last mo.

Aaron T. Chin et al. develop a temporal windowing methodology that groups recurrent sinusitis encounters into discrete episodes in electronic health records and improves #immunodeficiency classification. rupress.org/jhi/article/... #IEIs #Phenocopies #ClinicalPhenotypes #Diagnostics

We are shifting our clinical work in #ValleyFever into high gear! We received an NOA from #NIAID / #NIH for a R01 randomized placebo-controlled clinical trial using dupilumab (the "allergy medicine") to treat coccidioidomycosis as an adjunct to antifungals. Recently press highlight ucla.in/4qj52Zl

UCLA studies point to new way to fight potentially deadly Valley Fever

A series of recently published studies show why some people's immune systems are unable to fight off the potentially deadly Valley Fever.

uclahealth.org

Fantastic review of IL-17 family of ligands, receptors, and biology in @science.org from Sarah Gaffen @slg1717.bsky.social. I learned about the alternate IL17A receptor (RA/RD) that doesn't bind IL17F and the importance of A20 in regulating signaling. www.science.org/doi/10.1126/...

The tissue-specific regulation of immunobiology by IL-17 signaling

The tissue-specific roles and downstream signal transduction mechanisms of IL-17 in immunobiology are reviewed.

science.org

Studying hundreds of patients with severe coccidioidomycosis, we found two patterns of immune dysregulation. Th2 skewing affects about 25% of DCM (mostly males!), while T-cell exhaustion (like cancer) arises early during infection in those with DCM and causes reduced responses. Both are treatable!

JCI insight@insight.jci.org · 5mo ago

Two Research articles in this issue explore immune phenotypes from individuals with coccidioidomycosis including those with severe, life-threatening disease: doi.org/10.1172/jci.... & doi.org/10.1172/jci....

I spoke last week at the Univ. of California conference on AI and healthcare data about how we doctors will need to revalue human connection when we care for patients alongside AI. Connection for me brings energy and joy to the intellectual puzzles of the immune system. youtu.be/2yz6Z9ER_cQ?...

We are excited to share a cohort of 18 patients with severe #ValleyFever (coccidioidomycosis) treated with dupilumab and/or interferon gamma, extending our first report in NEJM 2020 (PMID: 32521134). Host-directed immunomodulation works to treat fungal infections as an adjunct to antifungals!

Clinical Infectious Diseases@cidjournal.bsky.social · 7mo ago

Immunomodulation in the Treatment of Disseminated Coccidioidomycosis ✅ Just Accepted 🔗 https://bit.ly/4t2DY0E

We have been working on the T cell dysregulation underlying coccidioidomycosis (Valley fever). Following up on our NEJM paper in 2020 (PMID: 32521134), we've now treated 18 patients at UCLA with immunomodulation (dupilumab and/or interferon gamma). We share a new case series doi.org/10.1093/cid/...

Immunomodulation in the Treatment of Disseminated Coccidioidomycosis

Severe coccidioidomycosis carries high mortality despite antifungals. We treated 18 refractory cases with immune modulation, including augmentation of Type

doi.org

This cool paper builds on the amazing work in hyaluronan and inflammation by @pbollyky.bsky.social's group at Stanford. His team published that a safe, small molecule could block HA synthesis, reduce HA in sputum (PMID: 35499083), and clinically improves lung fibrosis (PMID: 40451287)!

Science Magazine@science.org · 7mo ago

New work deciphers how disruptions to #lymphatic drainage drive fibrosis in transplanted lungs and hearts through the accumulation of hyaluronan—and identifies potential therapeutic targets to prevent lung fibrosis in mice. #ScienceTranslationalMedicine https://scim.ag/3ONyh7H

I'm so excited to share our new paper in Cell where we provided T cells two genes that allow metabolism of a safe form of glucose (derived from cellulose). This fuel allows human CAR-T cells to fight tumors better! Congrats go to Matt Miller, now a postdoc at Salk. www.cell.com/cell/fulltex...

Fungal-derived cellobiose metabolic pathway fuels T cells to bypass intratumoral glucose competition

Equipping T cells with fungal enzymes to utilize cellobiose (a safe and natural disaccharide of glucose obtained from the wood polymer cellulose) enhances their viability and effector function in tumo...

cell.com

Intriguing paper from @josephsunlab.bsky.social about IL12 signaling that comes *before* TCR signaling leading to memory. Re "delayed expression" of IL12R in CD8 T cells, I wonder if that's related to the change from short to full-length transcripts that occurs upon activation (see PMID: 23024274)?

Simon Grassmann 草人@simongrassmann.bsky.social · 8mo ago

Excited to share my paper published today in @cp-immunity.bsky.social! We find that when CTLs integrate antigen and cytokine signaling, the timing of these cues matters - shedding light on an old question: Why do NK cells sometimes behave like CD8+ T cells? www.sciencedirect.com/science/arti...

Yay! I'll be there, and speaking on our use of machine learning at UCLA to find undiagnosed patients with immune deficiency diseases.

Rohit Vashisht@rohitv.bsky.social · 9mo ago

UC Health CDI2 upcoming conference! Thriving through change: Adapting, Advancing, Achieving Stellar listening of speakers, likes of which include @kdpsingh.bsky.social! Register 👇 na.eventscloud.com/website/5224...

This is a fantastic article by the @fletcherlabucb.bsky.social at Berkeley about macrophages assessing and eating the cells they bump into based on their membrane tension. I wonder if regulatory T cells, which also perform trogocytosis, use a similar mechanism (not FcγR-based, obviously).

Fletcher Lab@fletcherlabucb.bsky.social · 10mo ago

How does a macrophage decide to eat or simply nibble? Check out our latest paper! You can also read this nice review. Congrats Caitlin for leading this amazing work! www.nature.com/articles/s41... www.nature.com/articles/s41...

Cool advance in the epigenetics of Lamarckism. I wonder if a recent history of infections in fathers-to-be can be encoded in the epigenetics of sperm and passed down as well (e.g., microRNAs or chromatin organization at interferon response genes after viral infection).

Science Magazine@science.org · 12mo ago

Male mice that exercise can pass their newly gained fitness on to male offspring. If the same holds true in humans, researchers say, fathers could help improve the health of any future children by staying in shape themselves. https://scim.ag/47igpZm

Melissa Lechner's group at UCLA identified both CD4+ (Tfh) and CD8+ (Tc1) T cells as drivers of the autoimmune diabetes that arises after anti-PD1 therapy, and showed the nonspecific JAK inhib ruxolitinib could prevent it! Wow. My suspicion is that targeting IFNg-STAT1 alone probably is enough.

Waggoner Lab@labwaggoner.bsky.social · last yr.

Polyfunctional T follicular helper cells drive checkpoint-inhibitor diabetes and are targeted by JAK inhibitor therapy @jci-insight.bsky.social insight.jci.org/articles/vie...

One the many advances in this incredible paper by Columbia's Milner and Izar labs shows that GOF variants in PIK3CD are not all that rare, including p.M285T that occurs in 1/8000, and is correlated with autoimmune diseases. There are many more APDS patients lurking out there! #IEI #raredisease

Cell - a Cell Press journal@cp-cell.bsky.social · last yr.

Now online! Scalable generation and functional classification of genetic variants in inborn errors of immunity to accelerate clinical diagnosis and treatment

New antifungals are much needed -- 41 of these patients receiving olorofim had coccidioidomycosis. #valleyfever

Oliver Cornely@olivercornely.bsky.social · last yr.

New hope for hard-to-treat fungal infections: Phase 2b results show #Olorofim is effective and well-tolerated in patients with few or no treatment options. Read in The Lancet Infectious Diseases 👉 www.sciencedirect.com/science/arti... #IFD #Antifungals #ClinicalTrials

@elisabethbik.bsky.social re Atl Butte www.kudoboard.com/boards/OMydG...

Kudoboard for Atul Butte | Kudoboard

Collaborate to create a unique, online memorial. Add memories, photos, or videos; invite others to contribute; visit online anytime and print it out as a book of remembrance.

kudoboard.com

⚠️ Effective Monday 2/10/25, NIH indirect rate capped at 15%. Applies to existing & future grants. —> Deep budget cuts & program closures coming to a university near you. Is this the break the glass moment for university administrators who have been silent so far about the attack on science?

Bravo to Paul Bollyky @pbollyky.bsky.social at Stanford for his lab's paper showing that complementary groups of phage can be mixed to provide broad and effective antimicrobial therapy against Pseudomonas and Staph infections. Brilliant work! www.nature.com/articles/s41...

A blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections - Nature Communications

The application of phage therapy for multidrug-resistant infections is mainly limited to personalized therapy due to the narrow host range of individual phages. Here, Kim et al. identify groups of pha...

nature.com