iiinova — where your digital self keeps evolving

Manish Butte @manishbutte.bsky.social · 02/09/2026

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

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Manish Butte @manishbutte.bsky.social · 31/08/2026

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

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Manish Butte @manishbutte.bsky.social · 16/08/2026

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

uclahealth.org

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.

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Manish Butte @manishbutte.bsky.social · 13/06/2026

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/...

science.org

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.

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Manish Butte @manishbutte.bsky.social · 26/05/2026

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!

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Manish Butte @manishbutte.bsky.social · 19/04/2026

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?...

Manish Butte speaking in front of slides

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Manish Butte @manishbutte.bsky.social · 28/03/2026

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!

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Manish Butte @manishbutte.bsky.social · 05/03/2026

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/...

doi.org

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

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Manish Butte @manishbutte.bsky.social · 02/03/2026

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)!

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Manish Butte @manishbutte.bsky.social · 25/02/2026

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...

cell.com

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...

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Manish Butte @manishbutte.bsky.social · 31/01/2026

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)?

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Manish Butte @manishbutte.bsky.social · 28/01/2026

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

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Manish Butte @manishbutte.bsky.social · 22/01/2026

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).

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Manish Butte @manishbutte.bsky.social · 13/10/2025

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).

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Manish Butte @manishbutte.bsky.social · 09/07/2025

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.

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Manish Butte @manishbutte.bsky.social · 21/06/2025

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

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Manish Butte @manishbutte.bsky.social · 18/06/2025

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

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Reposted by Manish Butte

David F. Warner @dwarnersoc.bsky.social · 07/02/2025

⚠️ 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?

grants.nih.gov

NOT-OD-25-068: Supplemental Guidance to the 2024 NIH Grants Policy Statement: Indirect Cost Rates

NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Supplemental Guidance to the 2024 NIH Grants Policy Statement: Indirect Cost Rates NOT-OD-25-068. OD

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