Clinical immunology最新文献

{"title":"Mechanisms of age-related Treg dysfunction in an arthritic environment","authors":"Taihei Nishiyama ,&nbsp;Ayako Ohyama ,&nbsp;Haruka Miki ,&nbsp;Hiromitsu Asashima ,&nbsp;Yuya Kondo ,&nbsp;Hiroto Tsuboi ,&nbsp;Hiroshi Ohno ,&nbsp;Hitoshi Shimano ,&nbsp;Isao Matsumoto","doi":"10.1016/j.clim.2024.110337","DOIUrl":"10.1016/j.clim.2024.110337","url":null,"abstract":"<div><p>Rheumatoid arthritis (RA) is an autoimmune disease characterized by a polyarticular synovitis. In recent years, elderly onset rheumatoid arthritis (EORA) has been increasing. Treg cells in RA have been reported to be dysfunctional, but the relationship between aging and their functional changes is unclear. Here, we found that Treg cells from EORA patients had increased percentages, but decreased activity compared to those from younger onset RA (YORA) patients. In experiments using arthritis model mice, decreased suppressive function and oxygen consumption rate (OCR) were observed in Treg cells only from old arthritic mice. Furthermore, type I interferon (IFN) signaling was upregulated in Treg cells from old GIA mice, and IFN-β decreased the suppressive function of Treg cells. Our findings demonstrate that increased type I IFN signaling in old Treg cells is induced only in the arthritic environment and relates to decreased suppressive function of Treg cells, gets involved in EORA.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110337"},"PeriodicalIF":4.5,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-IL12p40 autoantibodies in a teenage girl with multiple recurrent abscesses","authors":"Ana Paola Macias Robles ,&nbsp;Aristine Cheng ,&nbsp;Steven M. Holland ,&nbsp;Saul O. Lugo Reyes","doi":"10.1016/j.clim.2024.110335","DOIUrl":"10.1016/j.clim.2024.110335","url":null,"abstract":"<div><p>More frequent among adults, phenocopies may be caused by somatic mutations or anti-cytokine autoantibodies, mimicking the phenotypes of primary immunodeficiencies. A fourteen-year-old girl was referred for a two-year history of weight loss and multiple recurrent abscesses, complicated recurrent pneumonia, pyelonephritis, osteomyelitis, and septic shock, without fever. She had started with nausea, hyporexia, and weight loss, then with abscesses in her hands, knee, ankle, and spleen. She also developed a rib fracture and left thoracic herpes zoster. The patient was cachectic, with normal vital signs, bilateral crackles on chest auscultation, tumefaction of the knee joint, and poorly healed wounds in hands and chest, oozing a yellowish fluid. Chest computed tomography revealed multiple bilateral bronchiectases. Laboratory workup reported chronic anemia, leukocytosis, neutrophilia, mild lymphopenia, thrombocytosis, pan-hypergammaglobulinemia, and elevated acute serum reactants. Lymphocyte subsets were low but present. <em>Mycobacterium tuberculosis</em> was detected via polymerase chain reaction in a bone biopsy specimen from ankle osteomyelitis. Whole-exome sequencing failed to identify a monogenic defect. Interleukin-12 was found markedly elevated in the serum of the patient. Phosphorylation of STAT4, induced by increasing doses of IL-12, was neutralized by patient serum, confirming the presence of anti-IL12 autoantibodies. IL-12 and IL-23 are crucial cytokines in the defense against intracellular microorganisms, the induction of interferon-gamma production by lymphocytes, and other inflammatory functions. Patients who develop neutralizing serum autoantibodies against IL12 manifest late in life with weight loss, multiple recurrent abscesses, poor wound healing, and fistulae. Treatment with anti-CD20 monoclonal antibodies was effective.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110335"},"PeriodicalIF":4.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of neutrophils in autoimmune diseases","authors":"Zhuoshu Li ,&nbsp;Qianjin Lu","doi":"10.1016/j.clim.2024.110334","DOIUrl":"10.1016/j.clim.2024.110334","url":null,"abstract":"<div><p>Historically, neutrophils have been primarily regarded as short-lived immune cells that act as initial responders to antibacterial immunity by swiftly neutralizing pathogens and facilitating the activation of adaptive immunity. However, recent evidence indicates that their roles are considerably more complex than previously recognized. Neutrophils comprise distinct subpopulations and can interact with various immune cells, release granular proteins, and form neutrophil extracellular traps. These functions are increasingly recognized as contributing factors to tissue damage in autoimmune diseases. This review comprehensively examines the physiological functions and heterogeneity of neutrophils, their interactions with other immune cells, and their significance in autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, antineutrophil cytoplasmic antibody-associated vasculitis, multiple sclerosis, and others. This review aims to provide a deeper understanding of the function of neutrophils in the development and progression of autoimmune disorders.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110334"},"PeriodicalIF":4.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient subtyping analysis of baseline multi-omic data reveals distinct pre-immune states associated with antibody response to seasonal influenza vaccination","authors":"Cigdem Sevim Bayrak ,&nbsp;Christian V. Forst ,&nbsp;Drew R. Jones ,&nbsp;David J. Gresham ,&nbsp;Smruti Pushalkar ,&nbsp;Shaohuan Wu ,&nbsp;Christine Vogel ,&nbsp;Lara K. Mahal ,&nbsp;Elodie Ghedin ,&nbsp;Ted Ross ,&nbsp;Adolfo García-Sastre ,&nbsp;Bin Zhang","doi":"10.1016/j.clim.2024.110333","DOIUrl":"10.1016/j.clim.2024.110333","url":null,"abstract":"<div><p>Understanding the molecular mechanisms underpinning diverse vaccination responses is critical for developing efficient vaccines. Molecular subtyping can offer insights into heterogeneous nature of responses and aid in vaccine design. We analyzed multi-omic data from 62 haemagglutinin seasonal influenza vaccine recipients (2019–2020), including transcriptomics, proteomics, glycomics, and metabolomics data collected pre-vaccination. We performed a subtyping analysis on the integrated data revealing five subtypes with distinct molecular signatures. These subtypes differed in the expression of pre-existing adaptive or innate immunity signatures, which were linked to significant variation in baseline immunoglobulin A (IgA) and hemagglutination inhibition (HAI) titer levels. It is worth noting that these differences persisted through day 28 post-vaccination, indicating the effect of initial immune state on vaccination response. These findings highlight the significance of interpersonal variation in baseline immune status as a crucial factor in determining the effectiveness of seasonal vaccines. Ultimately, incorporating molecular profiling could enable personalized vaccine optimization.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110333"},"PeriodicalIF":4.5,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152166162400442X/pdfft?md5=b197e5b33782b0398c0c27e2a11fb373&pid=1-s2.0-S152166162400442X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pediatric lymphoproliferative disorders associated with inborn errors of immunity","authors":"Jinjun Cheng ,&nbsp;Blachy J. Dávila Saldaña ,&nbsp;Shanmuganathan Chandrakasan ,&nbsp;Michael Keller","doi":"10.1016/j.clim.2024.110332","DOIUrl":"10.1016/j.clim.2024.110332","url":null,"abstract":"<div><p>Both non-malignant and malignant lymphoproliferative disorders (LPD) are commonly seen in patients with inborn errors of immunity (IEI), which may be the presenting manifestations or may develop during the IEI disease course. Here we review the clinical, histopathological, and molecular features of benign and malignant LPD associated with IEI and recognize the diagnostic challenges.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110332"},"PeriodicalIF":4.5,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs in clinically healed lesions are potential cellular candidates for recurrence of psoriasis","authors":"Lu Peng ,&nbsp;Wenqi Liu ,&nbsp;Yufan Cheng ,&nbsp;Ling Chen ,&nbsp;Zhu Shen","doi":"10.1016/j.clim.2024.110328","DOIUrl":"10.1016/j.clim.2024.110328","url":null,"abstract":"<div><p>Biological antibodies targeting key cytokines such as IL-17 and IL-23 have revolutionized psoriasis outcome. However, the recurrence remains an urgent challenge to be addressed. Currently, most of the descriptions of skin T-cell characteristics in psoriasis are derived from lesional and non-lesional skin, and their characteristics in resolved lesions (clinically healed lesions) remain vague. In order to further elucidate the cellular mechanism of recurrence, we performed single-cell sequencing and multiplexed immunohistochemical staining of T-cell subsets in autologous resolved lesion (RL), on-site recurrent psoriatic lesion (PL), and adjacent normal-appearing skin (NS) of psoriasis. By comparing with PL and NS tissues, we identified three potential cellular candidates for recurrence in clinically healed lesions: IL-17A/F double producing T cells, unstable Tregs and quiescent TRMs. Our results provide research clues for elucidating the immunological recurrence mechanism of psoriasis, and further work is needed to deepen our findings.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110328"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141781130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders","authors":"Rohan Ameratunga ,&nbsp;Hilary Longhurst ,&nbsp;Euphemia Leung ,&nbsp;Richard Steele ,&nbsp;Klaus Lehnert ,&nbsp;See-Tarn Woon","doi":"10.1016/j.clim.2024.110320","DOIUrl":"10.1016/j.clim.2024.110320","url":null,"abstract":"<div><p>Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment.</p><p>Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis.</p><p>Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and <em>H. influenzae</em> type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23).</p><p>This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110320"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth","authors":"Xuejiao Ji ,&nbsp;Guixian Huang ,&nbsp;Ying Peng ,&nbsp;Juechu Wang ,&nbsp;Xia Cai ,&nbsp;Enzhuo Yang ,&nbsp;Liying Zhu ,&nbsp;Yuan Wu ,&nbsp;Wei Sha ,&nbsp;Feifei Wang ,&nbsp;Ling Shen ,&nbsp;Hongbo Shen","doi":"10.1016/j.clim.2024.110331","DOIUrl":"10.1016/j.clim.2024.110331","url":null,"abstract":"<div><p>Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, <em>Mycobacteria tuberculosis</em> (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137⁺Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137⁻Vγ2Vδ2 T-cells. In response to HMBPP, CD137⁺Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137⁻Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137⁺Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of <em>GM-CSF</em> and <em>de novo</em> production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in Mϕ. Concurrently, exosomes produced by CD137⁺Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137⁺Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110331"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent decrease of circulating T follicular helper cells correlates with disease severity in elderly patients with COVID-19","authors":"Yihan Wang ,&nbsp;Qiu Wang ,&nbsp;Furong He ,&nbsp;Nan Qiao ,&nbsp;Xuejun Li ,&nbsp;Liqun Wei ,&nbsp;Lingjin Sun ,&nbsp;Weiqian Dai ,&nbsp;Ying Li ,&nbsp;Xueyang Pang ,&nbsp;Jiayi Hu ,&nbsp;Chuan Huang ,&nbsp;Guangchen Yang ,&nbsp;Chongjie Pang ,&nbsp;Zhidong Hu ,&nbsp;Man Xing ,&nbsp;Chunxiao Wan ,&nbsp;Dongming Zhou","doi":"10.1016/j.clim.2024.110329","DOIUrl":"10.1016/j.clim.2024.110329","url":null,"abstract":"<div><p>Overwhelming evidence has shown that aging is a significant risk factor for COVID-19-related hospitalizations, death and other adverse health outcomes. Particular T cell subsets that susceptible to aging and associated with COVID-19 disease severity requires further elucidation. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. Adaptive immunity was assessed across the COVID-19 severity spectrum. Patients underwent age-dependent CD4⁺ T lymphopenia, preferential loss of circulating T follicular regulatory cells (cTfh) subsets including cTfh-em, cTfh-cm, cTfh1, cTfh2, cTfh17 and circulating T follicular regulatory cells (cTfr), which regulated antibody production through different pathways and correlated with COVID-19 severity, were observed. Moreover, vaccination improved cTfh-cm, cTfh2, cTfr proportion and promoted NAb production. In conclusion, the elderly had gone through age-dependent cTfh subsets deficiency, which impeded NAb production and enabled aggravation of COVID-19 to critical illness, whereas SARS-CoV-2 vaccine inoculation helped to rejuvenate cTfh, cTfr and intensify NAb responses.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110329"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of early life cytomegalovirus infection on the immune profile of children","authors":"Ilse Ekman ,&nbsp;Anna-Mari Schroderus ,&nbsp;Tytti Vuorinen ,&nbsp;Mikael Knip ,&nbsp;Riitta Veijola ,&nbsp;Jorma Toppari ,&nbsp;Jorma Ilonen ,&nbsp;Johanna Lempainen ,&nbsp;Tuure Kinnunen","doi":"10.1016/j.clim.2024.110330","DOIUrl":"10.1016/j.clim.2024.110330","url":null,"abstract":"<div><p>Cytomegalovirus (CMV) infection has a life-long impact on the immune system, particularly on memory T cells. However, the effect of early life CMV infection on the phenotype and functionality of T cells in infants and especially longitudinal changes occurring during childhood have not been explored in detail.</p><p>The phenotype and functionality of peripheral blood CD8+ and CD4+ T cells from children infected with CMV in early life (&lt; 6 months of age) was analyzed using high-dimensional flow cytometry. Samples from CMV IgG-seropositive (CMV+) children were collected at 6 months and 6 years of age and compared to samples from CMV-seronegative (CMV-) children.</p><p>Early life CMV infection caused multiple alterations within T cells. These include downregulation of CD28 expression and upregulation of CD57 expression within both CD27+ early and CD27- late effector memory CD8+ and CD4+ T-cells at 6 months of age. Of these changes, only alterations within the highly differentiated late effector memory compartment persisted at the age of 6 years.</p><p>Early life CMV-infection has a distinct impact on developing CD8+ and CD4+ memory T cell compartments. It appears to induce both temporary as well as longer-lasting alterations, which may affect the functionality of the immune system throughout life.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"266 ","pages":"Article 110330"},"PeriodicalIF":4.5,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S152166162400439X/pdfft?md5=931b03a110ce6e0633849a154751734a&pid=1-s2.0-S152166162400439X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}