Journal of Clinical Immunology最新文献

{"title":"Correction to: Successful Immune Reconstitution in a Patient with a TYK2 Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors.","authors":"Yelei Gao, Ya Wang, Lina Zhou, Ge Lv, Jie Yu, Luying Zhang, Yan Meng, Wenli He, Ran Chen, Xiaodong Zhao, Ying Dou","doi":"10.1007/s10875-024-01762-1","DOIUrl":"10.1007/s10875-024-01762-1","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"158"},"PeriodicalIF":7.2,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492187","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":"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, Gökhan 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/s10875-024-01759-w","DOIUrl":"10.1007/s10875-024-01759-w","url":null,"abstract":"<p><p>Molecular diagnosis of inborn errors of immunity (IEI) plays a critical role in determining patients' long-term prognosis, treatment options, and genetic counseling. Over the past decade, the broader utilization of next-generation sequencing (NGS) techniques in both research and clinical settings has facilitated the evaluation of a significant proportion of patients for gene variants associated with IEI. In addition to its role in diagnosing known gene defects, the application of high-throughput techniques such as targeted, exome, and genome sequencing has led to the identification of novel disease-causing genes. However, the results obtained from these different methods can vary depending on disease phenotypes or patient characteristics. In this study, we conducted whole-exome sequencing (WES) in a sizable cohort of IEI patients, consisting of 303 individuals from 21 different clinical immunology centers in Türkiye. Our analysis resulted in likely genetic diagnoses for 41.1% of the patients (122 out of 297), revealing 52 novel variants and uncovering potential new IEI genes in six patients. The significance of understanding outcomes across various IEI cohorts cannot be overstated, and we believe that our findings will make a valuable contribution to the existing literature and foster collaborative research between clinicians and basic science researchers.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"157"},"PeriodicalIF":4.4,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492188","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":"Lymphocyte-Directed Immunomodulation Remits Thymoma-Associated Autoimmune Pneumonitis.","authors":"Elise M N Ferré, Diana X Nichols-Vinueza, Lindsey B Rosen, Peter D Burbelo, Kevin P Fennelly, Joseph Pechacek, Daniel M Goldstein, Anahita Agharahimi, Annapurna Saksena, David E Kleiner, Yesim Yilmaz Demirdag, Arun Rajan, David S Schrump, Steven M Holland, Alexandra F Freeman, Michail S Lionakis","doi":"10.1007/s10875-024-01760-3","DOIUrl":"10.1007/s10875-024-01760-3","url":null,"abstract":"<p><strong>Background: </strong>Thymoma presents with several autoimmune manifestations and is associated with secondary autoimmune regulator (AIRE) deficiency. Pneumonitis has recently been described as an autoimmune manifestation associated with thymoma presenting with similar clinical, radiographic, histological, and autoantibody features as seen in patients with inherited AIRE deficiency who suffer from Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome.</p><p><strong>Objectives: </strong>To treat two patients with biopsy-proven thymoma-associated pneumonitis with lymphocyte-directed immunomodulation.</p><p><strong>Methods: </strong>Two patients with thymoma were enrolled on IRB-approved protocols at the NIH Clinical Center. We performed history and physical examination; laboratory, radiographic, histologic and pulmonary function evaluations; and measurement of the lung-directed autoantibodies KCNRG and BPIFB1 prior to and at 1- and 6-months following initiation of lymphocyte-directed immunomodulation with azathioprine with or without rituximab.</p><p><strong>Results: </strong>Combination T- and B-lymphocyte-directed immunomodulation resulted in improvement of clinical, functional, and radiographic parameters at 6-month follow-up evaluations in both patients with sustained remission up to 12-36 months following treatment initiation.</p><p><strong>Conclusion: </strong>Lymphocyte-directed immunomodulation remitted autoimmune pneumonitis in two patients with thymoma.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"156"},"PeriodicalIF":7.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492189","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":"Novel Mutation in the Moesin (MSN) Gene Leads to Immunodeficiency with Epstein-Barr Virus (EBV) Infection and Dermatomyositis-Like Symptoms.","authors":"Bijun Sun, Luyao Liu, Lingli Han, Qifan Li, Qi Wu, Jia Hou, Wenjie Wang, Wenjing Ying, Qinhua Zhou, Feng Qian, Wei Lu, Xiaochuan Wang, Jinqiao Sun","doi":"10.1007/s10875-024-01755-0","DOIUrl":"10.1007/s10875-024-01755-0","url":null,"abstract":"<p><strong>Purpose: </strong>Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype.</p><p><strong>Methods: </strong>Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays.</p><p><strong>Results: </strong>The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21^low B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls.</p><p><strong>Conclusions: </strong>The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"155"},"PeriodicalIF":7.2,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450614","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":"HLH and Recurrent EBV Lymphoma as the presenting manifestation of MAGT1 Deficiency: A Systematic Review of the Expanding Disease Spectrum.","authors":"Klevi Golloshi, William Mitchell, Deepak Kumar, Sakshi Malik, Suhag Parikh, Ahmed A Aljudi, Sharon M Castellino, Shanmuganathan Chandrakasan","doi":"10.1007/s10875-024-01749-y","DOIUrl":"10.1007/s10875-024-01749-y","url":null,"abstract":"<p><p>Magnesium transporter 1 (MAGT1) gene loss-of-function variants lead to X-linked MAGT1 deficiency with increased susceptibility to EBV infection and N-glycosylation defect (XMEN), a condition with a variety of clinical and immunological effects. In addition, MAGT1 deficiency has been classified as a congenital disorder of glycosylation (CDG) due to its unique role in glycosylation of multiple substrates including NKG2D, necessary for viral protection. Due to the predisposition for EBV, this etiology has been linked with hemophagocytic lymphohistiocytosis (HLH), however only limited literature exists. Here we present a complex case with HLH and EBV-driven classic Hodgkin lymphoma (cHL) as the presenting manifestation of underlying immune defect. However, the patient's underlying immunodeficiency was not identified until his second recurrence of Hodgkin disease, recurrent episodes of Herpes Zoster, and after he had undergone autologous hematopoietic stem cell transplant (HSCT) for refractory Hodgkin lymphoma. This rare presentation of HLH and recurrent lymphomas without some of the classical immune deficiency manifestations of MAGT1 deficiency led us to review the literature for similar presentations and to report the evolving spectrum of disease in published literature. Our systematic review showcased that MAGT1 predisposes to multiple viruses (including EBV) and adds risk of viral-driven neoplasia. The roles of MAGT1 in the immune system and glycosylation were highlighted through the multiple organ dysfunction showcased by the previously validated Immune Deficiency and Dysregulation Activity (IDDA2.1) score and CDG-specific Nijmegen Pediatric CDG Rating Scale (NPCRS) score for the patient cohort in the systematic review.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"153"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419328","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":"Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.","authors":"Zhaoyang Li, Andras Nagy, Dirk Lindner, Kim Duff, Enrique Garcia, Hakan Ay, Juan Carlos Rondon, Leman Yel","doi":"10.1007/s10875-024-01742-5","DOIUrl":"10.1007/s10875-024-01742-5","url":null,"abstract":"<p><strong>Purpose: </strong>Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically.</p><p><strong>Methods: </strong>This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint.</p><p><strong>Results: </strong>Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms.</p><p><strong>Conclusion: </strong>The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"148"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419365","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":"Severe Combined Immunodeficiency from a Homozygous DNA Ligase 1 Mutant with Reduced Catalytic Activity but Increased Ligation Fidelity.","authors":"Huda Alajlan, Vlad-Stefan Raducanu, Yossef Lopez de Los Santos, Muhammad Tehseen, Hibah Alruwaili, Amer Al-Mazrou, Reem Mohammad, Monther Al-Alwan, Alfredo De Biasio, Jasmeen S Merzaban, Hamoud Al-Mousa, Samir M Hamdan, Anas M Alazami","doi":"10.1007/s10875-024-01754-1","DOIUrl":"10.1007/s10875-024-01754-1","url":null,"abstract":"<p><p>A cell's ability to survive and to evade cancer is contingent on its ability to retain genomic integrity, which can be seriously compromised when nucleic acid phosphodiester bonds are disrupted. DNA Ligase 1 (LIG1) plays a key role in genome maintenance by sealing single-stranded nicks that are produced during DNA replication and repair. Autosomal recessive mutations in a limited number of individuals have been previously described for this gene. Here we report a homozygous LIG1 mutation (p.A624T), affecting a universally conserved residue, in a patient presenting with leukopenia, neutropenia, lymphopenia, pan-hypogammaglobulinemia, and diminished in vitro response to mitogen stimulation. Patient fibroblasts expressed normal levels of LIG1 protein but exhibited impaired growth, poor viability, high baseline levels of gamma-H2AX foci, and an enhanced susceptibility to DNA-damaging agents. The mutation reduced LIG1 activity by lowering its affinity for magnesium 2.5-fold. Remarkably, it also increased LIG1 fidelity > 50-fold against 3' end 8-Oxoguanine mismatches, exhibiting a marked reduction in its ability to process such nicks. This is expected to yield increased ss- and dsDNA breaks. Molecular dynamic simulations, and Residue Interaction Network studies, predicted an allosteric effect for this mutation on the protein loops associated with the LIG1 high-fidelity magnesium, as well as on DNA binding within the adenylation domain. These dual alterations of suppressed activity and enhanced fidelity, arising from a single mutation, underscore the mechanistic picture of how a LIG1 defect can lead to severe immunological disease.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"151"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419329","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":"18q Deletion Syndrome Presenting with Late-Onset Combined Immunodeficiency.","authors":"Sho Hashiguchi, Dan Tomomasa, Takuro Nishikawa, Shuji Ishikawa, Harumi Akaike, Hidehiko Kobae, Tsuyoshi Shirai, Toshikage Nagao, Kosuke Noma, Satoshi Okada, Kazuhiro Kamuro, Yasuhiro Okamoto, Hirokazu Kanegane","doi":"10.1007/s10875-024-01751-4","DOIUrl":"10.1007/s10875-024-01751-4","url":null,"abstract":"<p><p>Patients with chromosome 18q deletion syndrome generally experience hypogammaglobulinemia. Herein, we describe two patients with chromosome 18q deletion syndrome who presented with late-onset combined immune deficiency (LOCID), which has not been previously reported. Patient 1 was a 29-year-old male with 18q deletion syndrome, who was being managed for severe motor and intellectual disabilities at the Yamabiko Medical Welfare Center for 26 years. Although the patient had few infections, he developed Pneumocystis pneumonia at the age of 28. Patient 2, a 48-year-old female with intellectual disability and congenital malformations, was referred to Tokyo Medical and Dental University Hospital with abnormal bilateral lung shadows detected on her chest radiography. Computed tomography showed multiple lymphadenopathies and pneumonia. A lymph node biopsy of the inguinal region revealed granulomatous lymphadenitis, and a chromosomal examination revealed 18q deletion. Array-based genomic hybridization analysis revealed deletion at 18q21.32-q22.3 for patient 1 and at 18q21.33-qter for patient 2. Immune status work-up of the two patients revealed panhypogammaglobulinemia, decreased number of memory B cells and naïve CD4⁺ and/or CD8⁺ cells, reduced response on the carboxyfluorescein diacetate succinimidyl ester T-cell division test, and low levels of T-cell receptor recombination excision circles and Ig κ-deleting recombination excision circles. Consequently, both patients were diagnosed with LOCID. Although patients with 18q deletion syndrome generally experience humoral immunodeficiency, the disease can be further complicated by cell-mediated immunodeficiency, causing combined immunodeficiency. Therefore, patients with 18q deletion syndrome should be regularly tested for cellular/humoral immunocompetence.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"154"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419325","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":"Effective Management of XLA Associated Enteropathy with Vedolizumab Monotherapy.","authors":"Ekra Rai, Ali Doroudchi, Benjamin Nulsen, Ramee Younes, Caroline Y Kuo","doi":"10.1007/s10875-024-01747-0","DOIUrl":"10.1007/s10875-024-01747-0","url":null,"abstract":"","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"150"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419326","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":"Successful Immune Reconstitution in a Patient with a TYK2 Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors.","authors":"Yelei Gao, Ya Wang, Lina Zhou, Ge Lv, Jie Yu, Luying Zhang, Yan Meng, Wenli He, Ran Chen, Xiaodong Zhao, Ying Dou","doi":"10.1007/s10875-024-01753-2","DOIUrl":"10.1007/s10875-024-01753-2","url":null,"abstract":"<p><p>A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107α secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-α or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":"44 7","pages":"152"},"PeriodicalIF":7.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419364","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}