{"title":"BCL10 deficiency: Long-term immune reconstitution following hematopoietic stem cell transplantation.","authors":"Marwa Ali, Anas M Alazami, Hamoud Al-Mousa","doi":"10.70962/jhi.20260126","DOIUrl":"10.70962/jhi.20260126","url":null,"abstract":"<p><p>BCL10 deficiency is a rare combined immunodeficiency characterized by severe infections, chronic diarrhea, hypogammaglobulinemia, and impaired lymphocyte activation despite preserved lymphocyte counts. We report a novel homozygous BCL10 variant with durable cure and immune reconstitution following hematopoietic stem cell transplantation.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laure Delaval, Karim Dorgham, Jehane Fadlallah, Emilie Corvilain, Pierre-Emmanuel Rautou, Eric Oksenhendler, Claire Fieschi, Guy Gorochov, Marion Malphettes
{"title":"Higher serum sCD14 is an independent biomarker for porto-sinusoidal vascular disease risk in CVID.","authors":"Laure Delaval, Karim Dorgham, Jehane Fadlallah, Emilie Corvilain, Pierre-Emmanuel Rautou, Eric Oksenhendler, Claire Fieschi, Guy Gorochov, Marion Malphettes","doi":"10.70962/jhi.20260066","DOIUrl":"10.70962/jhi.20260066","url":null,"abstract":"<p><p>Serum soluble CD14 (sCD14) is used as a surrogate marker for bacterial translocation. This cohort study demonstrates that higher baseline sCD14 levels are an independent biomarker for porto-sinusoidal vascular disease risk in patients with common variable immunodeficiency.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V Koneti Rao, Anna Šedivá, Virgil A S H Dalm, Alessandro Plebani, Catharina Schuetz, Anna Shcherbina, Antonio Trizzino, Yulia Zharankova, Alanvin Orpia, Elaine Kulm, Julia Körholz, Vassilios Lougaris, Yulia Rodina, Jason Bradt, Anurag Relan, Gulbu Uzel
{"title":"Open-label extension study of leniolisib in activated PI3Kδ syndrome: Long-term efficacy and safety.","authors":"V Koneti Rao, Anna Šedivá, Virgil A S H Dalm, Alessandro Plebani, Catharina Schuetz, Anna Shcherbina, Antonio Trizzino, Yulia Zharankova, Alanvin Orpia, Elaine Kulm, Julia Körholz, Vassilios Lougaris, Yulia Rodina, Jason Bradt, Anurag Relan, Gulbu Uzel","doi":"10.70962/jhi.20260040","DOIUrl":"10.70962/jhi.20260040","url":null,"abstract":"<p><p>Activated phosphoinositide 3-kinase delta syndrome (APDS) is an inborn error of immunity characterized by immune deficiency and dysregulation. Leniolisib is a selective phosphoinositide 3-kinase delta inhibitor approved to treat APDS in patients ≥12 years old. We report final results from a single-arm, open-label extension study in 37 patients with APDS (NCT02859727). Median leniolisib exposure was 4.3 years (range, 1.2-7.0 years). Adverse events (AE) were reported in 34 patients; 87% were grade 1. Serious AEs, reported in 10 patients, were deemed unrelated to leniolisib. Two patients discontinued treatment due to AEs: cardiac arrest and Hodgkin's lymphoma. There were significant reductions in annual infection (P = 0.0005) and respiratory infection (P = 0.0017) rates per year of treatment. Immunoglobulin replacement therapy (IRT) use significantly decreased per year of treatment (P = 0.0095). Clinically meaningful improvements in general health scores from the 36-Item Short Form Survey were observed. Overall, long-term use of leniolisib was generally well tolerated, and infections and IRT use reduced over time.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophia Marie Armbruster, Andres Caballero-Oteyza, Oliver Bartsch, Tiziana Lorenzini, Hassan Abolhassani, Samantha Chan, Luis Ignacio González Granado, Victor Garcia-Bustos, Marta Dafne Cabañero Navalon, Nazanin Fathi, Nima Rezaei, Mathieu Fusaro, Roger Colobran, Kaan Boztug, Michele Proietti, Bodo Grimbacher
{"title":"Genotype-phenotype analysis in 333 individuals with heterozygous variants in NFKB1.","authors":"Sophia Marie Armbruster, Andres Caballero-Oteyza, Oliver Bartsch, Tiziana Lorenzini, Hassan Abolhassani, Samantha Chan, Luis Ignacio González Granado, Victor Garcia-Bustos, Marta Dafne Cabañero Navalon, Nazanin Fathi, Nima Rezaei, Mathieu Fusaro, Roger Colobran, Kaan Boztug, Michele Proietti, Bodo Grimbacher","doi":"10.70962/jhi.20260076","DOIUrl":"10.70962/jhi.20260076","url":null,"abstract":"<p><p>Heterozygous germline variants in NFKB1 can be classified into variants with \"known protein defect\" and \"unknown protein effect.\" However, beyond this, NFKB1 variants may be additionally categorized into at least eight distinct variant classes. We conducted a literature review of 67 papers reporting on NFKB1 variants and included four additional individuals, carrying previously unreported NFKB1 variants. We identified 333 individuals with unique variants in NFKB1. Our compiled data revealed that there is no sex predilection, the penetrance-including all heterozygous carriers-was 78%, and the mean age of onset for the \"known protein defect cohort\" was 21.2 years. Individuals harboring variants with a known protein defect demonstrated a higher frequency of malignancies and autoimmune disorders. However, these individuals were less frequently classified as affected than individuals with variants with unknown protein defect. Carriers of whole NFKB1 gene deletions had a significantly higher penetrance to being designated as \"affected,\" but beyond this, the clinical manifestations did not differ between variant classes.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2027-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Tomomasa, Tomoko Uehara, Tomotada Takayama, Madoka Nishimura, Ryosuke Wakatsuki, Xi Yang, Satoshi Okada, Akihiro Fujimoto, Hirokazu Kanegane
{"title":"A possible founder IRAK4 variant in Okinawa, Japan.","authors":"Dan Tomomasa, Tomoko Uehara, Tomotada Takayama, Madoka Nishimura, Ryosuke Wakatsuki, Xi Yang, Satoshi Okada, Akihiro Fujimoto, Hirokazu Kanegane","doi":"10.70962/jhi.20260119","DOIUrl":"10.70962/jhi.20260119","url":null,"abstract":"<p><p>A cluster of cases of IRAK4 deficiency has been identified in Okinawa Prefecture, Japan. All affected families carry the homozygous c.123_124insA variant, suggesting a founder effect and supporting the implementation of targeted newborn screening of IRAK4 deficiency in Okinawa.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13576643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renan César Sbruzzi, Adrian Gervais, Eduarda Sgarioni, Silvia Gress, Helena Suñé Lehmen, Martina Schroeder Wissmann, Bibiana Sampaio de Oliveira Fam, Nathan A Cadore, Mariléa F Feira, Osvaldo Artigalás, Giovanna Câmara Giudicelli, Lucy Bizien, Aurélie Cobat, Qian Zhang, Anne Puel, Paul Bastard, Jean-Laurent Casanova, Fernanda S L Vianna
{"title":"Autoantibodies neutralizing type I interferons in COVID-19 patients from southern Brazil.","authors":"Renan César Sbruzzi, Adrian Gervais, Eduarda Sgarioni, Silvia Gress, Helena Suñé Lehmen, Martina Schroeder Wissmann, Bibiana Sampaio de Oliveira Fam, Nathan A Cadore, Mariléa F Feira, Osvaldo Artigalás, Giovanna Câmara Giudicelli, Lucy Bizien, Aurélie Cobat, Qian Zhang, Anne Puel, Paul Bastard, Jean-Laurent Casanova, Fernanda S L Vianna","doi":"10.70962/jhi.20260096","DOIUrl":"10.70962/jhi.20260096","url":null,"abstract":"<p><p>Inborn errors of type I IFN (IFN-I) immunity and neutralizing autoantibodies (auto-Abs) against IFN-I (AAN-I-IFNs) impair antiviral immunity and underlie critical COVID-19. Their impact on disease severity in different populations, such as Latin American populations, remains to be better understood. This study assessed the presence of AAN-I-IFNs (anti-IFN-α2, anti-IFN-ω, and anti-IFN-β) in a cohort of 458 COVID-19 patients from southern Brazil, stratified as mild (n = 224) versus non-mild (n = 234), or survivors (n = 369) versus deceased (n = 89). AAN-I-IFNs were detected in 17 patients (3.7%), with increasing prevalence across disease severity, present in one (0.4%) mild case and 16 (6.8%) hospitalized cases (P = 0.006); and eight (2.2%) survivors and nine (10.1%) deceased cases (P = 0.008). Anti-IFN-α2 and anti-IFN-ω auto-Abs were most frequently detected, while anti-IFN-β auto-Abs were found in one patient. Our findings highlight the role of AAN-I-IFNs underlying COVID-19 severity in a southern Brazilian population.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Derrick H Y Chong, Caroline Spaner, Ibrahim Elsharawi, Mark Trinder, Haya Al Bitar, Mariam Goubran, Amelia Perrotta, Rachael Horner, Dilys Chen, Jennifer Corpuz, Kun Huang, Trudy Taylor, Ian Marie Lano, Kerri Purdy, Jan P Dutz, Sylvia Pasternak, Richard I Crawford, Luke Y C Chen
{"title":"Skin biopsy in adult-onset Still's disease: A specific, rapid, and widely available diagnostic test.","authors":"Derrick H Y Chong, Caroline Spaner, Ibrahim Elsharawi, Mark Trinder, Haya Al Bitar, Mariam Goubran, Amelia Perrotta, Rachael Horner, Dilys Chen, Jennifer Corpuz, Kun Huang, Trudy Taylor, Ian Marie Lano, Kerri Purdy, Jan P Dutz, Sylvia Pasternak, Richard I Crawford, Luke Y C Chen","doi":"10.70962/jhi.20260088","DOIUrl":"10.70962/jhi.20260088","url":null,"abstract":"<p><p>Adult-onset Still's disease (AOSD) is a diagnostic challenge, as its features overlap with many inflammatory syndromes and no single finding is diagnostic. Skin biopsies showing dyskeratotic keratinocytes (DKs) in the superficial epidermis, including the horny layer, are thought to be highly specific for AOSD but are not included in current diagnostic or classification criteria. We conducted a retrospective clinicopathological study of 16 adults with confirmed AOSD and skin biopsies from a Canadian rare diseases program, and developed a differential diagnosis for superficial DKs using expert consensus and literature review. Clinical morphology varied, but histopathology was similar: 12 of 16 patients had DKs or necrotic keratinocytes in the upper epidermis. Superficial DKs have been reported in conditions distinct from AOSD, but not in its major mimics. Skin biopsy is low-cost, minimally invasive, and widely available and should be performed early in suspected AOSD; superficial DKs should be added to future diagnostic and classification criteria.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TLR8 gain-of-function syndrome.","authors":"Hwi M Gil, Megan A Cooper","doi":"10.70962/jhi.20260172","DOIUrl":"10.70962/jhi.20260172","url":null,"abstract":"<p><p>Toll-like receptor 8 (TLR8) is an endosomal pattern recognition receptor highly expressed in myeloid cells that senses RNA degradation fragments. Monogenic gain-of-function (GOF) variants in TLR8 cause an inborn error of immunity (IEI) with a spectrum of immune-mediated pathology ranging from severe lymphoproliferation with neutropenia and bone marrow failure to anemia and autoimmunity. Half of identified patients have mosaic disease-causing variants, with variant allele fractions as low as 7% sufficient to drive systemic immune dysregulation. This, along with immunologic profiling of patients, demonstrates a dominant mechanism of disease, likely mediated by inflammatory cytokines. Disease-causing variants in TLR8 are enriched at or near agonist and antagonist binding sites in the encoded protein. As a spectrum of disease and genotypes emerges, identifying sensitivity to agonism and resistance to antagonism may provide insight into molecular mechanisms and therapeutic targets. Here, we review the genetics and clinical features of 19 reported cases of TLR8 GOF diseases, and future areas of investigation for this IEI.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High prevalence of autoantibodies neutralizing type I IFNs in Japanese patients with hepatitis C.","authors":"Maki Taniguchi, Chiaki Tao, Takaki Asano, Miyuki Tsumura, Ko Ko, Hiroko Kumada, Takanori Utsumi, Kosuke Noma, Fumiaki Sakura, Kosuke Ashihara, Moe Tamaura, Yoko Mizoguchi, Osamu Ohara, Dusan Bogunovic, Paul Bastard, Jean-Laurent Casanova, Junko Tanaka, Masataka Tsuge, Kazuaki Chayama, Shiro Oka, Satoshi Okada","doi":"10.70962/jhi.20250239","DOIUrl":"10.70962/jhi.20250239","url":null,"abstract":"<p><p>Autoantibodies neutralizing type I IFNs (AAN-I-IFNs) are being identified as major, common, and global determinants of a growing range of severe viral diseases. We examined whether persistent hepatitis C virus (HCV) infection, with or without IFN-α therapy, could induce AAN-I-IFNs. We tested 2,573 HCV patients aged 1-95 years (1,115 treated with IFN-α, 1,458 untreated) and 1,000 healthy controls. AAN-INF-α2 prevalence was significantly higher in hepatitis C patients (2.7%) than in healthy controls (0.7%) and was higher still in those treated with IFN-α (3.9%) than in untreated patients (1.9%) (P = 0.0053). A longitudinal study of 15 IFN-α-treated patients with AAN-IFN-α2 revealed that only one had AAN-IFN-α2 before IFN-α therapy and that 12 patients developed AAN-IFN-α2 in the year following treatment. However, 80% eventually became AAN-IFN-α2 negative. These findings suggest that chronic HCV infection, perhaps due to the chronic production of endogenous IFN-α, and exogenous IFN-α treatment promote the development of AAN-IFN-α2.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ambre Dethier, Fanny Bajolle, Paul Bastard, Laureline Berteloot, Romain Lévy, Filippo Consonni, Quentin Deletang, Eric Dannaoui, Olivier Raisky, Philippe Drabent, Jacinta Bustamante, Fréderic Rieux-Laucat, Anne Puel, Fanny Lanternier, Marie-Louise Frémond, Bénédicte Neven
{"title":"A fatal case of Aspergillus endocarditis in a pediatric patient with STING-associated vasculopathy.","authors":"Ambre Dethier, Fanny Bajolle, Paul Bastard, Laureline Berteloot, Romain Lévy, Filippo Consonni, Quentin Deletang, Eric Dannaoui, Olivier Raisky, Philippe Drabent, Jacinta Bustamante, Fréderic Rieux-Laucat, Anne Puel, Fanny Lanternier, Marie-Louise Frémond, Bénédicte Neven","doi":"10.70962/jhi.20250262","DOIUrl":"10.70962/jhi.20250262","url":null,"abstract":"<p><p>SAVI is a rare STING1 gain-of-function disorder causing systemic inflammation, vasculopathy, and interstitial lung disease. JAK inhibitors are first-line therapy. We report a SAVI patient on prolonged JAK inhibitors who developed opportunistic infections, including fatal Aspergillus endocarditis, underscoring therapeutic challenges.</p>","PeriodicalId":521015,"journal":{"name":"Journal of human immunity","volume":"2 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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