Clinical immunology最新文献

{"title":"Job's not done: BCG-itis as the first manifestation of hyper-IgE syndrome. A case report and review of the literature","authors":"Aidé Tamara Staines-Boone ,&nbsp;Edna Venegas-Montoya ,&nbsp;Jorge Alberto García Campos ,&nbsp;Jennifer Alejandra Obregón García ,&nbsp;Julieta C. Marmolejo Bjirsdorp ,&nbsp;Yuridia Salazar Gálvez ,&nbsp;Mario Ernesto Cruz-Muñoz ,&nbsp;Lizbeth Blancas Galicia ,&nbsp;Edgar Alejandro Medina-Torres ,&nbsp;Sara Elva Espinosa-Padilla ,&nbsp;Diana Olguín Calderón ,&nbsp;Laura Berrón-Ruiz ,&nbsp;Saul O. Lugo Reyes","doi":"10.1016/j.clim.2025.110639","DOIUrl":"10.1016/j.clim.2025.110639","url":null,"abstract":"<div><div>The <em>Bacille Calmette-Guérin</em> (BCG) vaccine is widely used to prevent tuberculosis (TB), especially in newborns and children in high TB prevalence areas. Though generally safe, it can cause adverse reactions like BCG-itis, a localized inflammatory response, and BCG-osis, a systemic infection. This case report details the clinical journey of a male toddler from a non-consanguineous family who presented with regional BCG-itis and later developed a disseminated mycobacterial infection. The patient had a history of recurrent suppurative otitis media and chronic granulomatous inflammation, with mycobacteria identified through biopsy. Despite initial treatments, he exhibited persistent and severe symptoms, including central nervous system abscesses, onychomycosis, and elevated serum Immunoglobulin E levels (13,160 IU/ml). Whole-exome sequencing identified a pathogenic heterozygous missense variant in <em>STAT3</em> exon 13 (c.1144C &gt; T, p.Arg382Trp), confirming autosomal dominant Hyper-IgE Syndrome. The patient showed improvement with antibiotics and intravenous immunoglobulin, yet struggled with relapses upon dose reduction of antitubercular drugs. The literature review revealed two similar cases, underscoring the importance of genetic and immunological insights in managing adverse vaccine reactions in Hyper-IgE Syndrome. CD4+ Th17 cells and interleukins 17, 21, 22, and 23 are crucial in fighting mycobacteria by activating autophagy in infected monocytes and MAIT cells. Type 2 interferon immunity and superoxide production are key in combating mycobacterial diseases like Mendelian Susceptibility to Mycobacterial Disease and Chronic Granulomatous Disease. Studies show that Asian and Latin American patients are overrepresented in non-tuberculous mycobacterial infections due to mandatory BCG vaccination at birth. It is recommended to contraindicate BCG vaccination in patients with known or suspected immune deficiencies and delay live vaccines until 6 months of age.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110639"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534394","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":"IMPDH2 facilitates CD4+ T cell activation through AKT/mTOR pathway by upregulating SRPK1 in myasthenia gravis","authors":"Yingjie Ren ,&nbsp;Tao Wu ,&nbsp;Zhaojun Liu ,&nbsp;Lifang Li ,&nbsp;Ying Li ,&nbsp;Guanghao Xin ,&nbsp;Shanshan Peng ,&nbsp;Jingyan Niu ,&nbsp;Biying Chen ,&nbsp;Hanlu Cai ,&nbsp;Qinghua Tian ,&nbsp;Lihua Wang ,&nbsp;Huixue Zhang","doi":"10.1016/j.clim.2025.110634","DOIUrl":"10.1016/j.clim.2025.110634","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Myasthenia gravis (MG) is a T cell-mediated autoimmune disease characterized by abnormal immune responses, particularly the hyperactivation of CD4+ T cells, which may disrupt signal transmission at the neuromuscular junction. Inosine-5′-monophosphate dehydrogenase-2 (IMPDH2) has been reported to participate in immune activation and is likely associated with T cells, but its role in the pathogenesis of MG remains unclear. Therefore, the present study aimed to elucidate the mechanism through which IMPDH2 regulates CD4+ T cells in MG.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, IMPDH2 expression was measured by qRT-PCR in peripheral blood mononuclear cells (PBMCs) collected from 60 MG patients and 60 healthy controls. Western blotting was additionally performed to detect IMPDH2 protein expression in six MG patients (three ocular and three generalized), compared with six healthy controls matched by age, gender, and sample collection time. CD4+ T cells were then isolated from PBMCs of MG patients and healthy controls by immunomagnetic bead sorting, and IMPDH2 expression was further analyzed by qRT-PCR. Subsequently, correlations between IMPDH2 expression levels and clinical indices (neutrophil and lymphocyte counts) as well as disease severity (Myasthenia Gravis Activities of Daily Living scores and Quantitative Myasthenia Gravis scores) were assessed. Additionally, flow cytometry, EdU assays, and CCK-8 assays were employed to evaluate the effects of IMPDH2 knockdown or overexpression on CD4+ T cell apoptosis and proliferation. The expression of apoptosis-related proteins was detected by western blotting. Mass spectrometry (MS), co-immunoprecipitation (Co-IP), and kinase inhibitor-based Co-IP validation assays were used to screen and verify proteins potentially interacting with IMPDH2 in CD4+ T cells. The colocalization of IMPDH2 and its binding proteins in CD4+ T cells was confirmed by confocal fluorescence microscopy and quantitative analysis. Furthermore, western blotting was performed to assess regulatory interactions between IMPDH2 and its binding proteins upon knockdown of either molecule. Western blotting was also used to detect protein levels within MG-related signaling pathways following IMPDH2 knockdown or overexpression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;IMPDH2 expression was significantly elevated in PBMCs and CD4+ T cells from MG patients compared with healthy controls. Clinical data analysis demonstrated a positive correlation between IMPDH2 expression and both lymphocyte and neutrophil counts in MG patients. Additionally, IMPDH2 expression positively correlated with MG disease severity. Functionally, upregulation or downregulation of IMPDH2 correspondingly promoted or suppressed CD4+ T cell proliferation and apoptosis. Mechanistically, direct interactions between IMPDH2 and SRPK1 were confirmed in vitro, and IMPDH2 was found to regulate SRPK1 expression, subsequently affecting CD4+ T cell prolifer","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110634"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488124","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":"Association of peripheral blood mitochondrial DNA gene variation and methylation levels with rheumatoid arthritis","authors":"Qian Huang ,&nbsp;Xue-Qian Cai ,&nbsp;Zhi-Qiang Li ,&nbsp;Yan Liu ,&nbsp;Hai-Feng Pan","doi":"10.1016/j.clim.2025.110641","DOIUrl":"10.1016/j.clim.2025.110641","url":null,"abstract":"<div><h3>Objective</h3><div>Mitochondrial dysfunction is closely related to the pathogenesis of various autoimmune diseases, and mitochondrial DNA (mtDNA) gene variations are associated with the susceptibility to autoimmune diseases. This study aimed to investigate association between mtDNA genetic variants, methylation levels and rheumatoid arthritis (RA).</div></div><div><h3>Method</h3><div>We performed mtDNA whole genome sequencing in 32 RA patients and 32 controls, and then validated 8 mtDNA variants using the SNaPshot™ multiplex technique in 452 RA patients and 457 controls. The methylation levels of 4 mtDNA genes were measured in 108 RA patients and 107 controls by MethylTarget technique.</div></div><div><h3>Results</h3><div>We found that <em>ND5</em> gene m.12705 T genotype, <em>tRNA-Pro</em> gene m.16304C genotype, <em>tRNA-Pro</em> gene m.16319 A genotype were significantly associated with RA susceptibility in entire population and female population. Moreover, the increased frequency of m.12705 T and the decreased frequency of m.16304C were significantly related to anti-CCP positive in RA patients. While <em>tRNA-Pro</em> gene m.16092 T &gt; C, m.16189 T &gt; C, <em>RNR2</em> gene m.2706 T &gt; G, <em>ND2</em> gene m.4833 A &gt; G, m.5108 T &gt; C showed no association with the risk of RA. When compared to controls, the methylation levels of <em>ND5, RNR2, ND2</em> genes were significantly decreased in RA patients. In addition, <em>ND5, RNR2</em> methylation levels were linked to erythrocyte sedimentation rate, and m.12705C &gt; T variant significantly influenced <em>ND5</em> methylation level among RA patients.</div></div><div><h3>Conclusion</h3><div>Multiple mtDNA variants in <em>ND5</em>, <em>tRNA-Pro</em> genes and methylation levels of <em>ND5, RNR2, ND2</em> genes were significantly associated with genetic susceptibility to RA in Chinese population.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110641"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556372","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":"Hypothalamic pituitary adrenal axis hormone changes during IL-17A inhibition with secukinumab in patients with psoriasis","authors":"F. Krefting ,&nbsp;S. Hölsken ,&nbsp;W. Sondermann ,&nbsp;M. Schedlowski","doi":"10.1016/j.clim.2025.110611","DOIUrl":"10.1016/j.clim.2025.110611","url":null,"abstract":"<div><h3>Purpose</h3><div>Secukinumab, an interleukin-17 A (IL-17 A) inhibitor, is an approved treatment for psoriasis, but effects on the hypothalamic pituitary adrenal (HPA) axis are unknown.</div></div><div><h3>Methods</h3><div>In a 16-week randomized controlled trial, 105 patients with psoriasis received secukinumab at either 300 or 75 mg. Plasma levels of IL-17 A, cortisol, adrenocorticotropic hormone, prolactin, dehydroepiandrosterone and perceived stress using Perceived Stress Scale (PSS-10) were measured at baseline and every four weeks. Treatment response was assessed using Psoriasis Area and Severity Index (PASI).</div></div><div><h3>Results</h3><div>Both dosage groups showed significant increases in IL-17 A and cortisol, with no differences between groups. Cortisol increased by approximately 33 %, indicating activation of HPA axis. Changes in cortisol did not correlate with PASI. PSS-10 inversely correlated with cortisol at baseline, and shifted positive during follow-up.</div></div><div><h3>Conclusion</h3><div>Secukinumab treatment in psoriasis is accompanied by HPA axis activation. Further studies are needed to determine the duration, mechanisms, and magnitude of this activation.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110611"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336815","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":"Compound heterozygous NFKB1 missense variants in cis associated with immunodeficiency","authors":"Manfred Fliegauf ,&nbsp;Kelly Nitschke ,&nbsp;Pavla Mrovecova ,&nbsp;Sara Posadas-Cantera ,&nbsp;Nadezhda Camacho-Ordonez ,&nbsp;Klaus Warnatz ,&nbsp;Baerbel Keller ,&nbsp;Bodo Grimbacher","doi":"10.1016/j.clim.2025.110637","DOIUrl":"10.1016/j.clim.2025.110637","url":null,"abstract":"<div><div>Heterozygous pathogenic <em>NFKB1</em> variants are one of the most frequent monogenic causes of disease in patients with inborn errors of immunity (IEI) and mainly compromise protein expression. <em>NFKB1</em> encodes the precursor protein p105, which is processed into p50, the key transcription factor of canonical NF-κB1 signaling. Insufficiency of p105/p50 presents with immunodeficiency and autoinflammation.</div><div>Here, we evaluated two <em>NFKB1</em> missense variants, identified in compound heterozygosity <em>in cis</em> (c.[150A&gt;C;156A&gt;C]; p.[Gln50His;Lys52Asn]) in a patient with immunodeficiency. While the isomorphic Q50H variant enhanced the rather marginal defect of K52N, the combination of both caused a pathogenic protein damage in p50. Our findings highlight an inherent challenge when analyzing single variants ‘isolated’ from their genetic context. Particularly when filtering out additional variants, <em>e.g.</em> based on allele frequencies, pathogenic effects originating from compound heterozygosity may be overlooked.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110637"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470831","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":"Plasma anti-ATP7A/B autoantibodies as potential biomarkers for the detection and prognosis of non-small cell lung cancer","authors":"Lulu Zhang ,&nbsp;Aichen Liu ,&nbsp;Peiqi Yu ,&nbsp;Jing Li ,&nbsp;Xiaobin Cao ,&nbsp;Yihao Liang ,&nbsp;Wenke Sun ,&nbsp;Songyun Ouyang ,&nbsp;Liping Dai ,&nbsp;Jingjing Liu","doi":"10.1016/j.clim.2025.110617","DOIUrl":"10.1016/j.clim.2025.110617","url":null,"abstract":"<div><div>Autoantibodies against tumor-associated antigens (TAAs) in the plasma have demonstrated potential as biomarkers for cancer detection and prognosis. Copper transport proteins ATP7A and ATP7B (copper ATPase transporter α and β peptides, respectively), identified as TAAs, are abnormally expressed in patients with non-small cell lung cancer (NSCLC) and represent potential diagnostic biomarkers. In this study, we aimed to evaluate the diagnostic and prognostic values of plasma autoantibodies targeting ATP7A/B in NSCLC. The expression levels of anti-ATP7A/B autoantibodies were detected in a verification group of 75 patients with NSCLC and 75 normal controls (NC) and confirmed in a validation group including 253 patients with NSCLC, 253 patients with benign pulmonary nodules (BPN), and 253 NC using the enzyme-linked immunosorbent assay method. The results showed that the expression levels of anti-ATP7A/B autoantibodies in patients with NSCLC were significantly higher than in those with BPN and in NC. The anti-ATP7A/B autoantibodies distinguished NSCLC from NC with AUC values of 0.785 (95 % CI: 0.746–0.824) and 0.849 (95 % CI: 0.816–0.882), respectively. Those autoantibodies distinguished NSCLC from BPN with AUC values of 0.772 (95 % CI: 0.731–0.812) and 0.777 (95 % CI: 0.736–0.817), respectively. Additionally, the combination of anti-ATP7A and anti-ATP7B autoantibodies improved the efficacy of NSCLC diagnosis with increased AUC values. The prognostic values of anti-ATP7A/B autoantibodies were analyzed in 356 patients with NSCLC. The anti-ATP7B autoantibody served as an independent prognostic predictor for NSCLC, as high expression levels predicted poor prognosis. In conclusion, this study demonstrated the potential benefits of anti-ATP7A/B autoantibodies as biomarkers for NSCLC detection and prognosis.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110617"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145414210","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":"Prognostic value of lymphocyte-to-monocyte ratio in relapsed/refractory adult T-cell Leukemia/lymphoma patients receiving mogamulizumab","authors":"Yutaka Shimazu ,&nbsp;Takuro Kameda ,&nbsp;Toshio Kitawaki ,&nbsp;Ayako Kamiunten ,&nbsp;Masaaki Sekine ,&nbsp;Hiroshi Kawano ,&nbsp;Seiichi Sato ,&nbsp;Kouichi Maeda ,&nbsp;Takanori Toyama ,&nbsp;Noriaki Kawano ,&nbsp;Kiyoshi Yamashita ,&nbsp;Masanori Takeuchi ,&nbsp;Junzo Ishizaki ,&nbsp;Kazuya Shimoda ,&nbsp;Akifumi Takaori-Kondo","doi":"10.1016/j.clim.2025.110616","DOIUrl":"10.1016/j.clim.2025.110616","url":null,"abstract":"<div><h3>Background</h3><div>Mogamulizumab, an anti-CCR4 monoclonal antibody, is approved for relapsed/refractory (r/r) aggressive adult T-cell leukemia/lymphoma (ATL), although durable responses are limited.</div></div><div><h3>Objective</h3><div>To identify biomarkers associated with mogamulizumab efficacy, focusing on host immune status and known prognostic factors.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 315 patients with r/r aggressive ATL using real-world data from Japan. Clinical and prognostic variables were analyzed for association with overall survival (OS), stratified by mogamulizumab use.</div></div><div><h3>Results</h3><div>Among 315 patients, 97 received mogamulizumab (Moga [+]). One-year OS was higher in Moga (+) than Moga (−) patients (51.2 % vs. 34.0 %, <em>p</em> = 0.006). Multivariate analysis identified age &lt; 70, PS 0–1, cCa &lt; 11 mg/dL, albumin ≥3.5 g/dL, LDH &lt; 265 IU/L, LMR ≥ 2.6, and Moga (+) use as independent predictors of OS. In Moga (+) patients, cCa and LMR remained independent prognostic factors.</div></div><div><h3>Conclusion</h3><div>LMR is a novel prognostic factor in r/r ATL and may provide useful information when considering mogamulizumab-based treatment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110616"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426464","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":"Oral live attenuated polio vaccines induce enhanced T-cell responses with broad antigen recognition compared to inactivated polio vaccines","authors":"Julia Snyder ,&nbsp;Marni Slavik ,&nbsp;Patrick Harvey ,&nbsp;Roxana Del Rio-Guerra ,&nbsp;Bernardo A. Mainou ,&nbsp;Alessandro Sette ,&nbsp;Beth D. Kirkpatrick ,&nbsp;Alba Grifoni ,&nbsp;Jessica W. Crothers","doi":"10.1016/j.clim.2025.110607","DOIUrl":"10.1016/j.clim.2025.110607","url":null,"abstract":"<div><h3>Summary</h3><div>Little is known about the immunologic mechanisms responsible for observed differences in mucosal immunity following vaccination with oral live attenuated polio vaccines (OPVs) compared to inactivated polio vaccines (IPVs). Here, we used a flow cytometric activation-induced marker (AIM)-based approach to investigate vaccine-related differences in T cell response using peripheral blood samples from healthy adults enrolled in two polio vaccine trials. Our findings indicate that vaccination with OPVs (1) enhances CD4+ T cell responses, and (2) expands CD4+ and CD8+ antigen recognition of non-structural proteins. Fecal shedding of OPVs was associated with enhanced T cell responses, and primary CD8+ T cell responses appear to correlate with early control of fecal viral shedding. Our results indicate that OPVs induce broad cellular immunity to polioviruses, which may help explain their enhanced ability to stimulate effective pathogen-specific mucosal immunity.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110607"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145279098","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":"Serum cytokine profiling identifies IL-17A and IL-10 as prognostic biomarkers for disease outcome in pediatric acute lymphoblastic leukemia","authors":"Qian Ye ,&nbsp;Jin Rao ,&nbsp;Li Zhang ,&nbsp;Muxia Yan ,&nbsp;Huishan Chen ,&nbsp;Yanping Yi ,&nbsp;Hua Jiang ,&nbsp;Xiaoliang Deng ,&nbsp;Yiqian Wang","doi":"10.1016/j.clim.2025.110638","DOIUrl":"10.1016/j.clim.2025.110638","url":null,"abstract":"<div><div>Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, yet reliable serum biomarkers for prognosis and relapse prediction remain limited. We profiled serum cytokines in 60 pediatric ALL patients and 19 healthy controls using the Aimplex Cytokine Assay, and evaluated predictive performance via receiver operating characteristic (ROC) analysis and least absolute shrinkage and selection operator (LASSO) regression. ALL patients exhibited significantly elevated levels of IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TNF-α compared with controls. Among these, IL-17A and IL-10 showed the strongest associations with disease severity and relapse risk, with higher baseline levels correlating with increased relapse probability (<em>p</em> = 0.02 and <em>p</em> = 0.005) and longer time to achieve remission in multivariate LASSO models. These findings identify IL-17A and IL-10 as promising prognostic biomarkers for pediatric ALL, with potential application in risk stratification and guiding individualized treatment strategies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110638"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476593","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":"Autoantibody fine specificity restriction is associated with clinical response in RA treated with abatacept and methotrexate","authors":"Pauline Brevet ,&nbsp;André Gillibert ,&nbsp;Léna Le Goaréguer ,&nbsp;Claire Lattard ,&nbsp;Laurent Drouot ,&nbsp;Rémi Varin ,&nbsp;Marie-Laure Golinski ,&nbsp;Sophie Candon ,&nbsp;Olivier Boyer ,&nbsp;Thierry Lequerré ,&nbsp;Olivier Vittecoq ,&nbsp;Manuel Fréret","doi":"10.1016/j.clim.2025.110610","DOIUrl":"10.1016/j.clim.2025.110610","url":null,"abstract":"<div><h3>Objective</h3><div>Anti-modified protein antibodies (AMPA) are central in rheumatoid arthritis (RA). We evaluated whether changes in fine specificities (FS) of anti-citrullinated protein antibodies (ACPA) and anti-CarP antibodies relate to clinical prognosis in RA patients treated with abatacept (ABA) plus methotrexate (MTX).</div></div><div><h3>Methods</h3><div>A multiplex bead immunoassay measured 6 ACPA FS and 1 anti-CarP FS in 59 anti-CCP+ RA patients (IgG, IgA). Disease activity (DAS28-CRP) and FS levels were assessed at baseline (M0) and 6 months (M6).</div></div><div><h3>Results</h3><div>After 6 months of ABA+MTX, several FS decreased with frequent negative seroconversion (NS). Higher baseline anti-citrullinated α-enolase (ACit-ENO1) IgG levels predicted better outcome (decrease of −0.17 DAS28 score per decile, 95 % CI −0.27 to −0.07, <em>p</em> = 0.03). Among patients with ≥1 positive FS at M0, a higher number of NS across 14 FS (IgG/IgA) correlated with greater improvement (−0.27 DAS28 score per antibody, 95 % CI −0.39 to −0.15, <em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>In this cohort of limited size, clinical response at M6 with ABA+MTX treatment was associated with the restriction of the autoantibody repertoire of IgG and IgA classes in RA patients.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110610"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353960","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}