Journal of Human Immunity

Journal of Human Immunity (JHI) @jhumimmunity.org is here! Read the inaugural editorial by @casanovalab.bsky.social outlining #JHI’s vision as the destination for groundbreaking research in human immunity and inborn errors of immunity. https://buff.ly/4hRGpOb #OpenAccess

Mørk, Jensen, Mogensen et al. investigated neutralizing IFN-I #autoantibodies in centenarians from Denmark, Colombia, Australia, and Japan and found that the prevalence of auto-Abs reaches a plateau in centenarians and declines in Japanese and females rupress.org/jhi/article/... #Autoimmunity

The ups and downs of human #UNC93B1: Autoimmune and viral conditions. New review from Elina Idiiatullina, Jean-Laurent Casanova @casanovalab.bsky.social, and Shen-Ying Zhang @shenyingzhang1.bsky.social @rockefeller.edu: rupress.org/jhi/article/... #InbornErrorsOfImmunity #autoimmunity

Jeffrey’s Insights: Next-generation sequencing for primary #immunodeficiency diagnosis, 2019–2025. New study from Jessica Quinn (Jeffrey Modell Foundation) and colleagues: rupress.org/jhi/article/... #Diagnostics #InbornErrorsOfImmunity

BCL10 deficiency: Long-term immune reconstitution following hematopoietic stem cell transplantation. New report from Marwa Ali, Anas M. Alazami, and Hamoud Al-Mousa (King Faisal Specialist Hospital & Research Center): rupress.org/jhi/article/... #InbornErrorsOfImmunity #HSCT

Santiago et al. utilize a large, limited, de-identified dataset to explore characteristics of patients with APDS. Hypertension was found in 28.5% of patients. There was variable usage of leniolisib- and leniolisib-treated patients had lower odds of hypertension. rupress.org/jhi/article/...

Ahuja et al. @newcastleuni.bsky.social describe three siblings with an #immunodeficiency who have a novel homozygous synonymous variant in DOCK2 that creates a defect in mRNA splicing, resulting in a frameshift and loss of DOCK2 protein expression rupress.org/jhi/article/... #InbornErrorsOfImmunity

Belaid et al. report the largest single-country cohort of RAG1/2 deficiency (n=128, Algeria). 2 founder variants explain 77% of cases, yet identical genotypes produced 3 different phenotypes. Mortality (89%) reflected transplant access, not diagnostic delay rupress.org/jhi/article/...

Genotype–phenotype analysis in 333 individuals with heterozygous variants in NFKB1. New study from Sophia Marie Armbruster, Bodo Grimbacher @uni-freiburg.de and colleagues: rupress.org/jhi/article/... #ClinicalPhenotypes

Disease associations for rare immune genetic variants require statistical or rule-based support. New study from Paul E. Gray (Western Sydney University), Stuart G. Tangye @garvaninstitute.bsky.social, and Edwin P. Kirk (UNSW Sydney): rupress.org/jhi/article/... #Autoimmunity #InbornErrorsOfImmunity

Pretransplant immune dysregulation and survival after #HSCT in pediatric inborn errors of immunity. New study from Andrés Soffia, Arturo Borzutzky, and Cristián Sotomayor (Pontificia Universidad Católica de Chile): rupress.org/jhi/article/... #InbornErrorsOfImmunity

Ackerman, @romberglab.bsky.social et al. describe recurrent, sterile inflammatory responses to surgery and trauma in a patient with a heterozygous, truncating NFKB1 variant. This case highlights the prospect of a targeted, personalized immunomodulatory therapy. rupress.org/jhi/article/...

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

Hitoshi Irabu, Masaki Shimizu et al. (Institute of Science Tokyo) identify low-VAF #KRAS variants in two children with systemic #lupus erythematosus and confirms both variants in independent blood samples. rupress.org/jhi/article/... #SLE

Higher serum sCD14 is an independent biomarker for porto-sinusoidal vascular disease risk in #CVID. New report from Laure Delaval, Guy Gorochov, Marion Malphettes @sorbonne-universite.fr @upcite.bsky.social and colleagues: rupress.org/jhi/article/... #ClinicalPhenotypes #InbornErrorsOfImmunity

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

Adults with IEI and their caregivers face a substantial occupational burden. A nationwide study in Italy from Pulvirenti et al. highlights work impairment, healthcare demands and unmet workplace needs and identifies actionable targets to support work participation. rupress.org/jhi/article/... #IEIs

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

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

Using CRISPR/Cas9, Webbers, Rojas-Rodriguez, Kuijpers @amsterdamumc.bsky.social et al. show that disruption of kindlin-3 in cultured #neutrophils largely recapitulates the LAD-III phenotype but some effector functions remain upon stimulation without intact kindlin-3. rupress.org/jhi/article/...

Open-label extension study of #leniolisib in activated PI3Kδ syndrome: Long-term efficacy and safety. New study from V. Koneti Rao, Gulbu Uzel @charlesuni.cuni.cz and colleagues: rupress.org/jhi/article/... #InbornErrorsOfImmunity

Idiiatullina, @casanovalab.bsky.social, and @shenyingzhang1.bsky.social review how, in humans, #UNC93B1 maintains a delicate balance between host defense and tolerance to self. rupress.org/jhi/article/... #InbornErrorsOfImmunity #Autoimmunity

The Jeffrey Modell Foundation’s “Jeffrey’s Insights” next-generation sequencing (NGS) program demonstrates that, for trained clinical immunologists, NGS yields significant diagnostic and clinical value, improving patient care and outcomes. rupress.org/jhi/article/... #InbornErrorsOfImmunity

Ali, Alazami, and Al-Mousa describe a novel case of human BCL10 deficiency with a 13-year follow-up after hematopoietic stem cell transplantation. Their findings expand the clinical and genetic spectrum of this ultra-rare immunodeficiency rupress.org/jhi/article/... #InbornErrorsOfImmunity #HSCT

Highly neutralizing anti–IFN-ω #autoantibodies underlie severe pediatric #adenovirus infection. New study from Chen-Xuan Kang, Cheng-Lung Ku, Chen-Yen Kuo and colleagues (Chang Gung University, Taiwan): rupress.org/jhi/article/... #Infections

Sophia Marie Armbruster, Bodo Grimbacher @uni-freiburg.de et al. review all published patients with NFKB1 variants. Variants were divided into subcohorts & classified into distinct variant classes, & correlative analyses searched for genotype–phenotype correlations rupress.org/jhi/article/...

Paul E. Gray, Stuart G. Tangye, and Edwin P. Kirk question the claimed autoimmune disease associations of heterozygous genetic variants in TNIP1 P2RY8 BLK BANK1 and SH2B3, which lack statistical support and where the allele frequency is too high for a Mendelian effect. rupress.org/jhi/article/...

Andrés Soffia, Arturo Borzutzky, and Cristián Sotomayor show that pretransplant immune dysregulation, quantified using IDDA v2.1, predicts overall survival after #HSCT in children with #InbornErrorsOfImmunity. rupress.org/jhi/article/...

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

Delaval et al. show that higher serum soluble CD14, a surrogate marker for bacterial translocation, and IgA deficiency are independent and early predictive biomarkers for porto-sinusoidal vascular disease risk in patients with common variable immunodeficiency. rupress.org/jhi/article/... #CVID

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

#Autoantibodies neutralizing type I interferons in older twin pairs: Low concordance. New study from Signe Bedsted Clemmensen, Nanna Mørk, Trine H. Mogensen @au.dk and colleagues: rupress.org/jhi/article/... #Infections #Autoimmunity

Lakkaraja and Schmitt et al. observe that IL-10 receptor deficiency is a life-threatening inborn error of immunity associated with early-onset #IBD and find that employing #HSCT results in excellent survival with full donor engraftment. rupress.org/jhi/article/... #InbornErrorsOfImmunity

#Leniolisib, a PI3Kδ inhibitor, improves the pathophysiology of APDS. In @jhumimmunity.org, Rao, Uzel @charlesuni.cuni.cz et al. demonstrate the safety and efficacy of leniolisib in patients with APDS ≥12 years of age receiving up to 7 years of treatment. rupress.org/jhi/article/...

#Leniolisib, a PI3Kδ inhibitor, improves the pathophysiology of APDS. Rao, Uzel @charlesuni.cuni.cz et al. demonstrate the safety and efficacy of leniolisib in patients with APDS ≥12 years of age receiving up to 7 years of treatment. rupress.org/jhi/article/... #InbornErrorsOfImmunity

Our new IRF4 paper follows all 10 known patients with the p.T95R variant: profound combined immunodeficiency, severe infections, and progressive lung disease. HSCT can be curative, but timing matters. Thanks to our international team and the families.

Chen-Xuan Kang, Cheng-Lung Ku, Chen-Yen Kuo et al. describe a case of neutralizing anti–IFN-ω #autoantibodies impairing antiviral defense and driving severe #adenovirus #pneumonia in a child. rupress.org/jhi/article/... #Infections

#Autoantibodies neutralizing type I interferons in #COVID19 patients from Southern Brazil. New study from Renan César Sbruzzi, Fernanda S.L. Vianna @ufrgs.br and colleagues: rupress.org/jhi/article/... #Infections #Phenocopies @casanovalab.bsky.social

How I Treat: Transplantation for primary immune regulatory diseases and inflammatory disorders. From Joseph Hai Oved @columbiamed.bsky.social: rupress.org/jhi/article/... #Infections #autoantibodies #HowITreat

Iglesias-Herrero, Schrijvers et al. longitudinally assess JAK-inhibitor treatment response in two patients w/ #STAT1 gain-of-function & show that it induces rapid but incomplete immune reconstitution, w/ increased TCR diversity and reversal of monocyte hyperinflammation. rupress.org/jhi/article/...

Clemmensen, Mørk, Mogensen et al. investigated the heredity of IFN-I #autoantibodies in adults in a large Danish twin cohort of 1,318 twin pairs. Overall, the data do not support a strong familial aggregation, as reflected by a low concordance rate for IFN-I auto-Abs. rupress.org/jhi/article/...

Management change following NGS diagnosis of inborn errors of immunity: The Australasian experience. Shruti Swamy, Paul E. Gray, Stuart G. Tangye and colleagues: rupress.org/jhi/article/... #ClinicalPhenotypes #Therapeutics #InbornErrorsOfImmunity #Diagnostics

Life-threatening hepatic complications in children with ADA-SCID. New report from Ridhima Aggarwal, Konstantinos Vazouras and colleagues @ucl.ac.uk: rupress.org/jhi/article/... #InbornErrorsOfImmunity #ADASCID #SCID

Antibody deficiency in #MyotonicDystrophy type 1: A differential diagnosis below the radar. New report from Edoardo Galli, Mike Recher and colleagues @biomedizin.unibas.ch @unibas.ch: rupress.org/jhi/article/... #InbornErrorsOfImmunity

#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

Swamy, Gray, Tangye et al. describe an Australian/New Zealand cohort where identification of monogenic #InbornErrorsOfImmunity through next-generation sequencing resulted in management change in 84% of cases including guiding #HSCT and initiating targeted treatment. rupress.org/jhi/article/...

Mosaic #TLR8 gain-of-function in an elderly female treated with JAK inhibitor and adjunctive therapy. New report from Jenny A. Patel, Megan A. Cooper @macattacklab.bsky.social, Ofer Zimmerman and colleagues @washumedicine.bsky.social: rupress.org/jhi/article/... #InbornErrorsOfImmunity