Journal of Clinical Immunology最新文献

{"title":"Similar Kinetics of Pulmonary SARS-CoV-2 Load in Intensive Care Unit Patients with COVID-19 Pneumonia with or Without Autoantibodies Neutralizing Type I Interferons.","authors":"Valentine Le Stang, Paul Bastard, Elise Langouet, Marc Pineton de Chambrun, Juliette Chommeloux, Adrian Gervais, Lucy Bizien, Anne Puel, Aurélie Cobat, Julien Mayaux, Alexandre Demoule, Jean-Laurent Casanova, David Boutolleau, Alain Combes, Sonia Burrel, Charles-Edouard Luyt","doi":"10.1007/s10875-024-01839-x","DOIUrl":"10.1007/s10875-024-01839-x","url":null,"abstract":"<p><strong>Purpose: </strong>The pathogenesis of life-threatening coronavirus disease 2019 (COVID-19) pneumonia in ICU patients can involve pre-existing auto-antibodies (auto-Abs) neutralizing type I interferons (IFNs). The impact of these auto-Abs on SARS-CoV-2 clearance in the lower respiratory tract (LRT) is unclear.</p><p><strong>Methods: </strong>We performed a retrospective study in 99 ICU patients with COVID-19 pneumonia between March and May 2020. LRT SARS-CoV-2 load (intensity and duration) was analyzed according to the presence or not of circulating auto-Abs neutralizing type I IFNs.</p><p><strong>Results: </strong>Among the 99 included patients, 38 (38%) were positive for auto-Abs neutralizing type I IFNs, with 5 (5%) harboring auto-Abs neutralizing IFN-α2 at any concentration, while 33 (33%) had auto-Abs neutralizing only IFN-ω at the lower concentration. SARS-CoV-2 load in the LRT and duration of viral shedding, were similar in patients with or without auto-Abs neutralizing type I IFNs. Patients with auto-Abs had the same mortality than those without auto-Abs, despite greater occurrence of renal failure and ECMO support, and longer duration of mechanical ventilation and ICU stay.</p><p><strong>Conclusion: </strong>In summary, 5% of patients with critical COVID-19 pneumonia carried auto-Abs neutralizing IFN-α2, while about 1/3 harbored auto-Abs neutralizing low concentrations of IFN-ω. The detection of either type of auto-Abs did not impact LRT viral clearance and mortality, although it was associated with greater morbidity and a longer hospitalization. These findings suggest that similar albeit hitherto unknown mechanisms of disease drive critical COVID-19 pneumonia in patients without auto-Abs against type I IFNs.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"45"},"PeriodicalIF":7.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Spectrum of Immune Abnormalities in VICI Syndrome.","authors":"Erin L Frost, Laura Lucas Youngblood, Yuki Hammers, Taylor Fitch, Bojana Pencheva, Shanmuganathan Chandrakasan","doi":"10.1007/s10875-024-01830-6","DOIUrl":"https://doi.org/10.1007/s10875-024-01830-6","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"44"},"PeriodicalIF":7.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.","authors":"Zehra Busra Azizoglu, Royala Babayeva, Zehra Sule Haskologlu, Mustafa Burak Acar, Serife Ayaz-Guner, Fatma Zehra Okus, Mohammad Bilal Alsavaf, Salim Can, Kemal Erdem Basaran, Mehmed Fatih Canatan, Alper Ozcan, Hasret Erkmen, Can Berk Leblebici, Ebru Yilmaz, Musa Karakukcu, Mehmet Kose, Ozlem Canoz, Ahmet Özen, Elif Karakoc-Aydiner, Serdar Ceylaner, Gülsüm Gümüş, Huseyin Per, Hakan Gumus, Halit Canatan, Servet Ozcan, Figen Dogu, Aydan Ikinciogullari, Ekrem Unal, Safa Baris, Ahmet Eken","doi":"10.1007/s10875-024-01832-4","DOIUrl":"10.1007/s10875-024-01832-4","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"43"},"PeriodicalIF":7.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab in a 9-week-old with Netherton Syndrome Leads to Deep Symptom Control.","authors":"Yannik Vollmuth, Narjes Abdulhameed Alelq, Franziska Sattler, Susanne Schmidt, Fabian Hauck","doi":"10.1007/s10875-024-01837-z","DOIUrl":"10.1007/s10875-024-01837-z","url":null,"abstract":"<p><strong>Purpose: </strong>Netherton syndrome (NS) is a rare inborn error of immunity (IEI) with an incidence of approximately 1:200,000 and the phenotypic triad of trichorrhexis invaginate (bamboo hair), congenital ichthyosiform erythroderma, and multiple atopic manifestations. Treatment options especially in infants are scarce and generally not licensed.</p><p><strong>Methods: </strong>Case report of a 9-week-old infant with NS treated with dupilumab off-label.</p><p><strong>Results: </strong>We report rapid and sustained resolution of allergic inflammation, deep symptom control including normalization of the skin microbiome, and catch-up somatic and psychomotor development without adverse drug reactions.</p><p><strong>Conclusion: </strong>Due to the high complication rate of NS, especially in the first years of life, we recommend treatment with dupilumab off-label immediately after the diagnosis has been established.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"42"},"PeriodicalIF":7.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Genetic Evaluation of the Patients with Clinically Diagnosed Inborn Errors of Immunity by Whole Exome Sequencing: Results from a Specialized Research Center for Immunodeficiency in Türkiye.","authors":"Baran Erman, Umran Aba, Canberk Ipsir, Damla Pehlivan, Caner Aytekin, Gokhan Cildir, Begum Cicek, Ceren Bozkurt, Sidem Tekeoglu, Melisa Kaya, Cigdem Aydogmus, Funda Cipe, Gulsan Sucak, Sevgi Bilgic Eltan, Ahmet Ozen, Safa Barıs, Elif Karakoc-Aydiner, Ayca Kıykım, Betul Karaatmaca, Hulya Kose, Dilara Fatma Kocacık Uygun, Fatih Celmeli, Tugba Arikoglu, Dilek Ozcan, Ozlem Keskin, Elif Arık, Elif Soyak Aytekin, Mahmut Cesur, Ercan Kucukosmanoglu, Mehmet Kılıc, Mutlu Yuksek, Zafer Bıcakcı, Saliha Esenboga, Deniz Çagdaş Ayvaz, Asena Pınar Sefer, Sukrü Nail Guner, Sevgi Keles, Ismail Reisli, Ugur Musabak, Nazlı Deveci Demirbas, Sule Haskologlu, Sara Sebnem Kilic, Ayse Metin, Figen Dogu, Aydan Ikinciogulları, Ilhan Tezcan","doi":"10.1007/s10875-024-01841-3","DOIUrl":"10.1007/s10875-024-01841-3","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"41"},"PeriodicalIF":7.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of X-Linked Agammaglobulinaemia Patients.","authors":"Ben Shillitoe, Jaime S Rosa Duque, Sophie H Y Lai, Tsun Ming Lau, Jeffery C H Chan, Helen Bourne, Catherine Stroud, Terry Flood, Matthew Buckland, Winnie Ip, Austen Worth, Scott Hackett, Archana Herwadkar, Tanya Coulter, Catherine Blaney, Stephen Jolles, Tomaz Garcez, Eduardo Moya, Saul Faust, Mark S Pearce, Yu Lung Lau, Andrew R Gennery","doi":"10.1007/s10875-024-01829-z","DOIUrl":"https://doi.org/10.1007/s10875-024-01829-z","url":null,"abstract":"<p><strong>Background: </strong>X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.</p><p><strong>Objectives: </strong>To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies.</p><p><strong>Methods: </strong>Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed.</p><p><strong>Results: </strong>99 patients with a median age of 29.02 years (IQR 12.83-37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04-8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT).</p><p><strong>Conclusions: </strong>Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"40"},"PeriodicalIF":7.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unidentified Fever and Persistent Liver Dysfunction in a Patient with X-Linked Agamaglobulinemia.","authors":"Yishi Zhang, Lang Yu, Yu Zhang, Xuemei Tang, Xiaodong Zhao, Yunfei An","doi":"10.1007/s10875-024-01834-2","DOIUrl":"https://doi.org/10.1007/s10875-024-01834-2","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"39"},"PeriodicalIF":7.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A large cohort from an immunology reference center and an algorithm for the follow-up of chronic neutropenia.","authors":"Canan Caka, Damla Nur Ergenoğlu, Nidanur Sinanoğlu, Ibrahim Cemal Maslak, Hacer Neslihan Bildik, Begüm Çiçek, Saliha Esenboga, Ilhan Tezcan, Deniz Cagdas","doi":"10.1007/s10875-024-01816-4","DOIUrl":"https://doi.org/10.1007/s10875-024-01816-4","url":null,"abstract":"<p><p>Chronic neutropenia causes involve nutritional deficiencies and inborn errors of immunity(IEI), such as severe congenital neutropenia. To classify common chronic neutropenia causes in a pediatric immunology unit. We enrolled 109 chronic neutropenia patients admitted to a pediatric immunology department between 2002-2022. We recorded clinical/laboratory features and genetic characteristics. The male/female ratio was 63/46. Fifty-eight patients had parental consanguinity(57.4%). 26.6% (n = 29) patients had at least one individual in their family with neutropenia. Common symtpoms at presentation were upper respiratory tract infections(URTI)(31.1%), oral aphthae(23.6%), skin infections(23.6%), pneumonia(20.8%), and recurrent abscesses(12.3%). Common infections during follow-up were URTI(56.8%), pneumonia(33%), skin infections(25.6%), gastroenteritis(18.3%), and recurrent abscesses(14,6%). Common long-term complications were dental problems(n = 51), osteoporosis(n = 22), growth retardation(n = 14), malignancy(n = 16)[myelodysplastic syndrome(n = 10), large granulocytic leukemia(n = 1), acute lymphoblastic leukemia(n = 1), Hodgkin lymphoma(n = 1), EBV-related lymphoma(n = 1), leiomyosarcoma(n = 1), and thyroid neoplasm(n = 1)]. We performed a genetic study in 86 patients, and 69(71%) got a genetic diagnosis. Common gene defects were HAX-1(n = 26), ELA-2 (ELANE)(n = 10), AP3B1(n = 4), and ADA-2(n = 4) gene defects. The IEI ratio(70.6%) was high. GCSF treatment(93.4%), immunoglobulin replacement therapy(18.7%), and HSCT(15.9%) were the treatment options. The mortality rate was 12.9%(n = 14). The most common long term complications were dental problems that is three times more common in patients with known genetic mutations. We prepared an algorithm for chronic neutropenia depending on the present cohort. An important rate of inborn errors of immunity, especially combined immunodeficiency(11.9%) was presented in addition to congenital phagocytic cell defects. Early diagnosis will allow us tailor the disease-specific treatment options sooner, preventing irreversible consequences.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"38"},"PeriodicalIF":7.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endophilin A2 Deficiency Impairs Antibody Production in Humans.","authors":"Cybel Mehawej, Eliane Chouery, Roula Farah, Alia Khalil, Setrida El Hachem, Sandra Corbani, Valerie Delague, Issam Mansour, Tarek Najemdeen, Rima Korban, Wissam H Faour, Gerard Lefranc, Andre Megarbane","doi":"10.1007/s10875-024-01827-1","DOIUrl":"https://doi.org/10.1007/s10875-024-01827-1","url":null,"abstract":"<p><p>Endophilin A2, the sole endophilin A family member expressed in hematopoietic cells, regulates various aspects of membrane dynamics, including autophagy and endocytosis. Recent studies in rodents highlight the essential role of endophilin A2 in modulating immune responses. Here we report a homozygous frameshift variant in the SH3GL1 gene (NM_003025.3:c.427delC; p.Leu143Serfs*9), detected by whole exome sequencing in a 14-year-old boy with predominantly antibody deficiency. The patient who is issued from a consanguineous Lebanese family, presents since the age of 18 months with recurrent respiratory tract infections, low peripheral B cell counts and pan-hypogammaglobulinemia, with no history of opportunistic infections. This defect is associated with decrease in switched memory B cells development, impaired in-vitro B cell proliferation and diminished in-vitro IgG production. The detected variant in SH3GL1 segregates with the disease in the family. It significantly decreases the expression of the protein in the patient's peripheral blood compared to healthy controls, thus confirming its pathogenicity. Interestingly, endophilin A2-deficient Sh3gl1^-/- mice have been reported to present defects in germinal center B cell responses and in the production of high-affinity IgG. Our data suggests that endophilin A2 deficiency impairs antibody production in humans. Reporting further cases with mutations in SH3GL1 is needed to better characterize the inborn error of immunity linked to this gene.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"37"},"PeriodicalIF":7.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polysaccharide, Conjugate, and mRNA-based Vaccines are Immunogenic in Patients with Netherton Syndrome.","authors":"Anouk E M Nouwen, Luca M Zaeck, Renske Schappin, Daryl Geers, Lennert Gommers, Susanne Bogers, Willem A Dik, Suzanne G M A Pasmans, Corine H GeurtsvanKessel, Rory D de Vries, Virgil A S H Dalm","doi":"10.1007/s10875-024-01828-0","DOIUrl":"10.1007/s10875-024-01828-0","url":null,"abstract":"<p><strong>Background: </strong>Netherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency.</p><p><strong>Methods: </strong>Vaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls.</p><p><strong>Results: </strong>None of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls.</p><p><strong>Conclusions: </strong>Vaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"45 1","pages":"36"},"PeriodicalIF":7.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}