Pub Date : 2025-11-01DOI: 10.1016/j.clim.2025.110635
Erik Cimé-Aké , Guadalupe Lima , Emilio Godínez-Lazarini , Sandra Juárez , Hilda Marín-López , Daniela Flores-Hernández , Ileana Flores-Hernández , Amairani Gómez-Rodríguez , Diego F. Hernández-Ramírez , Luis Llorente , Hilda Fragoso-Loyo
The objective was to assess the expression of senescence and exhaustion markers in CD4+ and CD8+ T-cell subsets, along with the p16INK4a gene, in patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI), compared with SLE patients without CI and healthy controls (HC). All participants underwent a standardized neurocognitive test battery, and CI was defined as performance ≥2 SD below the normative mean in ≥1 cognitive domain. The expression of immunosenescence and exhaustion markers was assessed by flow cytometry; expression of p16INK4a was assessed by qPCR. The SLE-CI group demonstrated a higher CD4+/CD8+ inverted ratio and increased p16INK4a expression. Compared with both SLE patients without CI and HC, SLE-CI patients exhibited reduced expression of CTLA-4+, LAG-3+, and PD-L1+ on CD4+ T-cells, as well as decreased PD-L1+ and TIM-3+ expression on CD8+ T-cells. Immunosenescence and T-cell exhaustion may contribute to the pathogenesis of CI in SLE.
{"title":"Immunosenescent and exhausted T cells in systemic lupus erythematosus patients with cognitive impairment","authors":"Erik Cimé-Aké , Guadalupe Lima , Emilio Godínez-Lazarini , Sandra Juárez , Hilda Marín-López , Daniela Flores-Hernández , Ileana Flores-Hernández , Amairani Gómez-Rodríguez , Diego F. Hernández-Ramírez , Luis Llorente , Hilda Fragoso-Loyo","doi":"10.1016/j.clim.2025.110635","DOIUrl":"10.1016/j.clim.2025.110635","url":null,"abstract":"<div><div>The objective was to assess the expression of senescence and exhaustion markers in CD4<sup>+</sup> and CD8<sup>+</sup> T-cell subsets, along with the p16<sup>INK4a</sup> gene, in patients with systemic lupus erythematosus (SLE) and cognitive impairment (CI), compared with SLE patients without CI and healthy controls (HC). All participants underwent a standardized neurocognitive test battery, and CI was defined as performance ≥2 SD below the normative mean in ≥1 cognitive domain. The expression of immunosenescence and exhaustion markers was assessed by flow cytometry; expression of p16<sup>INK4a</sup> was assessed by qPCR. The SLE-CI group demonstrated a higher CD4<sup>+</sup>/CD8<sup>+</sup> inverted ratio and increased p16<sup>INK4a</sup> expression. Compared with both SLE patients without CI and HC, SLE-CI patients exhibited reduced expression of CTLA-4<sup>+</sup>, LAG-3<sup>+</sup>, and PD-L1<sup>+</sup> on CD4<sup>+</sup> T-cells, as well as decreased PD-L1<sup>+</sup> and TIM-3<sup>+</sup> expression on CD8<sup>+</sup> T-cells. Immunosenescence and T-cell exhaustion may contribute to the pathogenesis of CI in SLE.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110635"},"PeriodicalIF":3.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145437712","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}
Pub Date : 2025-10-31DOI: 10.1016/j.clim.2025.110632
Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen
Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.
{"title":"Natural history of clinical manifestations in activated phosphoinositide 3-kinase δ syndrome (APDS): Time-to-event analyses using the European Society for Immunodeficiencies-APDS registry","authors":"Maria Elena Maccari , Sven Kracker , Anita Chandra , Stephan Ehl , Markus G. Seidel , Joanne Tutein Nolthenius , Laura J. Clark , Jennifer Page , Annabel Griffiths , John Whalen","doi":"10.1016/j.clim.2025.110632","DOIUrl":"10.1016/j.clim.2025.110632","url":null,"abstract":"<div><div>Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110632"},"PeriodicalIF":3.8,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430450","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}
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.
Objective
To identify biomarkers associated with mogamulizumab efficacy, focusing on host immune status and known prognostic factors.
Methods
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.
Results
Among 315 patients, 97 received mogamulizumab (Moga [+]). One-year OS was higher in Moga (+) than Moga (−) patients (51.2 % vs. 34.0 %, p = 0.006). Multivariate analysis identified age < 70, PS 0–1, cCa < 11 mg/dL, albumin ≥3.5 g/dL, LDH < 265 IU/L, LMR ≥ 2.6, and Moga (+) use as independent predictors of OS. In Moga (+) patients, cCa and LMR remained independent prognostic factors.
Conclusion
LMR is a novel prognostic factor in r/r ATL and may provide useful information when considering mogamulizumab-based treatment.
背景：Mogamulizumab是一种抗ccr4单克隆抗体，被批准用于复发/难治性（r/r）侵袭性成人t细胞白血病/淋巴瘤（ATL），尽管持久的反应有限。目的：鉴定与mogamulizumab疗效相关的生物标志物，重点关注宿主免疫状态和已知预后因素。方法：我们回顾性分析了日本315例r/r侵袭性ATL患者的真实数据。分析临床和预后变量与总生存期（OS）的相关性，并按mogamulizumab的使用进行分层。结果：315例患者中，97例患者接受了mogamulizumab （Moga[+]）治疗。Moga（+）组1年OS高于Moga（-）组（51.2 % vs. 34.0 %,p = 0.006）。结论：LMR是r/r ATL的一个新的预后因素，在考虑莫加珠单抗治疗时可能提供有用的信息。
{"title":"Prognostic value of lymphocyte-to-monocyte ratio in relapsed/refractory adult T-cell Leukemia/lymphoma patients receiving mogamulizumab","authors":"Yutaka Shimazu , Takuro Kameda , Toshio Kitawaki , Ayako Kamiunten , Masaaki Sekine , Hiroshi Kawano , Seiichi Sato , Kouichi Maeda , Takanori Toyama , Noriaki Kawano , Kiyoshi Yamashita , Masanori Takeuchi , Junzo Ishizaki , Kazuya Shimoda , 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 < 70, PS 0–1, cCa < 11 mg/dL, albumin ≥3.5 g/dL, LDH < 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":"2025-10-30","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}
Pub Date : 2025-10-24DOI: 10.1016/j.clim.2025.110617
Lulu Zhang , Aichen Liu , Peiqi Yu , Jing Li , Xiaobin Cao , Yihao Liang , Wenke Sun , Songyun Ouyang , Liping Dai , Jingjing Liu
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.
{"title":"Plasma anti-ATP7A/B autoantibodies as potential biomarkers for the detection and prognosis of non-small cell lung cancer","authors":"Lulu Zhang , Aichen Liu , Peiqi Yu , Jing Li , Xiaobin Cao , Yihao Liang , Wenke Sun , Songyun Ouyang , Liping Dai , 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":"2025-10-24","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}
Pub Date : 2025-10-24DOI: 10.1016/j.clim.2025.110615
Jinny Tsang , Avid Mohammadi , Sareh Bagherichimeh , Yoojin Choi , Azadeh Fazel , Elizabeth Tevlin , Sanja Huibner , Sara V. Good , Wangari Tharao , Bryan Coburn , Rupert Kaul
Elevated cervicovaginal cytokines/chemokines and epithelial disruption are associated with HIV risk. While penile-vaginal sex induces transient cervicovaginal inflammation and epithelial disruption, there is considerable interindividual heterogeneity. We defined genital inflammation using a multi-cytokine score and hypothesized that sex-induced inflammation would depend on the pre-existing vaginal immune milieu. We quantified HIV-associated immune factors in cervicovaginal secretions of HIV-uninfected women before and 1 h after penile-vaginal sex. Cervicovaginal IgA and IgG increased after sex, and baseline IgA was associated with inflammatory cytokines and epithelial disruption. Post-sex vaginal immune factors strongly associated and clustered with pre-sex concentrations, and participants with baseline inflammation remained inflamed after sex. Sex induced greater relative changes in inflammatory cytokines and epithelial disruption among participants with lower baseline levels, but not in chemokines. In conclusion, the baseline vaginal milieu determines the inflammatory effects of sex; specifically, sex elicits a greater change in inflammatory responses in women with baseline vaginal immunoquiescence.
{"title":"The baseline vaginal immune milieu is an important determinant of the inflammatory response induced by penile-vaginal sex","authors":"Jinny Tsang , Avid Mohammadi , Sareh Bagherichimeh , Yoojin Choi , Azadeh Fazel , Elizabeth Tevlin , Sanja Huibner , Sara V. Good , Wangari Tharao , Bryan Coburn , Rupert Kaul","doi":"10.1016/j.clim.2025.110615","DOIUrl":"10.1016/j.clim.2025.110615","url":null,"abstract":"<div><div>Elevated cervicovaginal cytokines/chemokines and epithelial disruption are associated with HIV risk. While penile-vaginal sex induces transient cervicovaginal inflammation and epithelial disruption, there is considerable interindividual heterogeneity. We defined genital inflammation using a multi-cytokine score and hypothesized that sex-induced inflammation would depend on the pre-existing vaginal immune milieu. We quantified HIV-associated immune factors in cervicovaginal secretions of HIV-uninfected women before and 1 h after penile-vaginal sex. Cervicovaginal IgA and IgG increased after sex, and baseline IgA was associated with inflammatory cytokines and epithelial disruption. Post-sex vaginal immune factors strongly associated and clustered with pre-sex concentrations, and participants with baseline inflammation remained inflamed after sex. Sex induced greater relative changes in inflammatory cytokines and epithelial disruption among participants with lower baseline levels, but not in chemokines. In conclusion, the baseline vaginal milieu determines the inflammatory effects of sex; specifically, sex elicits a greater change in inflammatory responses in women with baseline vaginal immunoquiescence.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110615"},"PeriodicalIF":3.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463283","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}
Pub Date : 2025-10-21DOI: 10.1016/j.clim.2025.110610
Pauline Brevet , André Gillibert , Léna Le Goaréguer , Claire Lattard , Laurent Drouot , Rémi Varin , Marie-Laure Golinski , Sophie Candon , Olivier Boyer , Thierry Lequerré , Olivier Vittecoq , Manuel Fréret
Objective
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).
Methods
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).
Results
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, p = 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, p < 0.0001).
Conclusions
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.
目的：抗修饰蛋白抗体（AMPA）在类风湿关节炎（RA）中起中心作用。我们评估了抗瓜氨酸蛋白抗体（ACPA）和抗鲤鱼抗体的精细特异性（FS）变化是否与阿巴接受（ABA）加甲氨蝶呤（MTX）治疗的RA患者的临床预后有关。方法：采用多头免疫分析法检测59例抗ccp + RA患者（IgG、IgA）的6个ACPA FS和1个anti-CarP FS。在基线（M0）和6 个月（M6）时评估疾病活度（DAS28-CRP）和FS水平。结果：ABA+MTX治疗6 个月后，几个FS下降，血清转化阴性（NS）频繁发生。基线抗瓜氨酸α-烯醇化酶（ACit-ENO1） IgG水平越高，预后越好（DAS28评分每十分位数降低-0.17,95% % CI -0.27至-0.07,p = 0.03）。在M0≥1阳性FS的患者中，14个FS （IgG/IgA）中NS数量越多，改善程度越高（每个抗体DAS28评分-0.27,95% % CI -0.39至-0.15,p ）。结论：在这个规模有限的队列中，ABA+MTX治疗在M6时的临床反应与RA患者IgG和IgA类自身抗体库的限制有关。
{"title":"Autoantibody fine specificity restriction is associated with clinical response in RA treated with abatacept and methotrexate","authors":"Pauline Brevet , André Gillibert , Léna Le Goaréguer , Claire Lattard , Laurent Drouot , Rémi Varin , Marie-Laure Golinski , Sophie Candon , Olivier Boyer , Thierry Lequerré , Olivier Vittecoq , 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> < 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":"2025-10-21","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}
Pub Date : 2025-10-18DOI: 10.1016/j.clim.2025.110611
F. Krefting , S. Hölsken , W. Sondermann , M. Schedlowski
Purpose
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.
Methods
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).
Results
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.
Conclusion
Secukinumab treatment in psoriasis is accompanied by HPA axis activation. Further studies are needed to determine the duration, mechanisms, and magnitude of this activation.
目的：Secukinumab是一种白细胞介素-17 A （IL-17 A）抑制剂，是一种被批准的银屑病治疗药物，但对下丘脑-垂体-肾上腺（HPA）轴的影响尚不清楚。方法：在一项为期16周的随机对照试验中，105例银屑病患者接受300或75 mg的secukinumab治疗。在基线和每四周测量血浆IL-17 A、皮质醇、促肾上腺皮质激素、催乳素、脱氢表雄酮水平和感知应激量表（PSS-10）。使用银屑病面积和严重程度指数（PASI）评估治疗效果。结果：两剂量组IL-17 A和皮质醇均显著升高，组间无差异。皮质醇升高约33% %，表明HPA轴被激活。皮质醇的变化与PASI无关。PSS-10与皮质醇在基线时呈负相关，在随访期间转为正相关。结论：Secukinumab治疗银屑病伴HPA轴激活。需要进一步的研究来确定这种激活的持续时间、机制和程度。
{"title":"Hypothalamic pituitary adrenal axis hormone changes during IL-17A inhibition with secukinumab in patients with psoriasis","authors":"F. Krefting , S. Hölsken , W. Sondermann , 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":"2025-10-18","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}
Pub Date : 2025-10-18DOI: 10.1016/j.clim.2025.110612
Jesús Daniel Zambrano-Romero , Diana Berenice Ríos-Ramírez, Verónica Yutsil García-Rasilla, Blanca Estela Ruiz-Medina, Paula Licona-Limón
Transforming growth factor β (TGF-β) is recognized as an anti-inflammatory cytokine that negatively affects effector CD8 T cells. However, its impact is not confined to the effector CD8 T cell population; TGF-β also plays a role in suppressing naïve CD8 T cell activation, preserving stemness, and influencing the function and differentiation of memory CD8 T cells. Memory CD8 T cells are vital for eradicating pathogens that have previously infected the host. Both tissue-resident and central memory CD8 T cells have demonstrated a dependency on TGF-β for their differentiation. The mechanisms underlying many of these TGF-β effects remain unclear. This review summarizes the roles of TGF-β in various CD8 T cell subsets, with an emphasis on the memory T cell compartment, and discusses recent findings regarding its influence on memory CD8 T cell differentiation as well as open questions in the field.
{"title":"TGF-β: A silent player regulating CD8 T cell memory","authors":"Jesús Daniel Zambrano-Romero , Diana Berenice Ríos-Ramírez, Verónica Yutsil García-Rasilla, Blanca Estela Ruiz-Medina, Paula Licona-Limón","doi":"10.1016/j.clim.2025.110612","DOIUrl":"10.1016/j.clim.2025.110612","url":null,"abstract":"<div><div>Transforming growth factor β (TGF-β) is recognized as an anti-inflammatory cytokine that negatively affects effector CD8 T cells. However, its impact is not confined to the effector CD8 T cell population; TGF-β also plays a role in suppressing naïve CD8 T cell activation, preserving stemness, and influencing the function and differentiation of memory CD8 T cells. Memory CD8 T cells are vital for eradicating pathogens that have previously infected the host. Both tissue-resident and central memory CD8 T cells have demonstrated a dependency on TGF-β for their differentiation. The mechanisms underlying many of these TGF-β effects remain unclear. This review summarizes the roles of TGF-β in various CD8 T cell subsets, with an emphasis on the memory T cell compartment, and discusses recent findings regarding its influence on memory CD8 T cell differentiation as well as open questions in the field.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110612"},"PeriodicalIF":3.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336785","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}
Pub Date : 2025-10-16DOI: 10.1016/j.clim.2025.110613
Islam M. Ghazi , Ahmed F. Omar , Wasim S. El Nekidy , Gehan Harb , Diaa Alrahmany
Introduction
Inherited hematological disorders, affecting immune cell quantity and function, compromise immune system efficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited enzymopathy and has been implicated in compromised immune cell function and host defense, and in elevating infection vulnerability. This study explores the impact of G6PD deficiency on immune cellular response and infection-related mortality.
Method
Adults with G6PD deficiency and bacterial infections (2017–2021) were analyzed. Demographics, comorbidities, laboratory parameters, and microbiological data were assessed. Cox proportional hazards regression analyzed the association between white blood cell (WBC) count and 28-day mortality. The data analysis was conducted using the R software statistical programming language.
Results
The investigation included 334 bacterial infection episodes representing 202 unique patients who fulfilled the inclusion criteria. A 19.2 % 28-day mortality rate was observed. Males, those aged ≥60, and patients with comorbidities had higher mortality. Anemia, high globulin, and elevated liver enzymes were associated with mortality. The majority of patients demonstrated reduced WBC counts (<9.8 × 109/L) during infection, significantly contributing to increased mortality risk (HR: 1.95, p = 0.008). Males exhibited a more pronounced impact. This study reveals heightened mortality risk in G6PD-deficient patients with diminished WBC counts during infections. Elevated CRP, globulins, and liver enzymes indicated severe infections, contrasting the unexpected non-response in WBC counts.
Conclusion
Vigilance in treating infections in G6PD-deficient patients, especially in males, is crucial for favorable outcomes. Diagnostic reliance on altered WBC counts in this population may misguide clinical decisions. G6PD deficiency poses a unique challenge in infection management, emphasizing the need for tailored interventions and exploration of alternative biomarkers for assessing severity and predicting mortality. Further studies and larger cohorts are essential for a comprehensive understanding and improved clinical practices.
简介：遗传性血液病，影响免疫细胞的数量和功能，损害免疫系统的效率。葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症是最常见的x连锁遗传性酶病，与免疫细胞功能和宿主防御受损以及感染易感性升高有关。本研究探讨G6PD缺乏对免疫细胞反应和感染相关死亡率的影响。方法：分析2017-2021年G6PD缺乏症和细菌感染的成年人。评估了人口统计学、合并症、实验室参数和微生物学数据。Cox比例风险回归分析白细胞（WBC）计数与28天死亡率之间的关系。数据分析采用R软件统计编程语言进行。结果：调查包括334例细菌感染事件，代表202例符合纳入标准的独特患者。28天死亡率为19.2 %。年龄≥60岁的男性和有合并症的患者死亡率较高。贫血、高球蛋白和肝酶升高与死亡率相关。大多数患者在感染期间表现出白细胞计数减少（9/L），这显著增加了死亡风险（HR: 1.95, p = 0.008）。男性表现出更明显的影响。该研究揭示了感染期间WBC计数减少的g6pd缺陷患者的死亡风险增加。升高的CRP，球蛋白和肝酶表明严重感染，与WBC计数的意外无反应形成对比。结论：警惕治疗g6pd缺陷患者，尤其是男性患者的感染，是获得良好结果的关键。在这一人群中，对白细胞计数改变的诊断依赖可能会误导临床决策。G6PD缺乏症对感染管理提出了独特的挑战，强调需要量身定制的干预措施和探索替代生物标志物来评估严重程度和预测死亡率。进一步的研究和更大的队列对于全面理解和改进临床实践是必不可少的。
{"title":"Innate immune response to bacterial infections in hospitalized glucose-6-phosphate dehydrogenase-deficient patients; diagnostic value of white blood cell count","authors":"Islam M. Ghazi , Ahmed F. Omar , Wasim S. El Nekidy , Gehan Harb , Diaa Alrahmany","doi":"10.1016/j.clim.2025.110613","DOIUrl":"10.1016/j.clim.2025.110613","url":null,"abstract":"<div><h3>Introduction</h3><div>Inherited hematological disorders, affecting immune cell quantity and function, compromise immune system efficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common X-linked inherited enzymopathy and has been implicated in compromised immune cell function and host defense, and in elevating infection vulnerability. This study explores the impact of G6PD deficiency on immune cellular response and infection-related mortality.</div></div><div><h3>Method</h3><div>Adults with G6PD deficiency and bacterial infections (2017–2021) were analyzed. Demographics, comorbidities, laboratory parameters, and microbiological data were assessed. Cox proportional hazards regression analyzed the association between white blood cell (WBC) count and 28-day mortality. The data analysis was conducted using the R software statistical programming language.</div></div><div><h3>Results</h3><div>The investigation included 334 bacterial infection episodes representing 202 unique patients who fulfilled the inclusion criteria. A 19.2 % 28-day mortality rate was observed. Males, those aged ≥60, and patients with comorbidities had higher mortality. Anemia, high globulin, and elevated liver enzymes were associated with mortality. The majority of patients demonstrated reduced WBC counts (<9.8 × 10<sup>9</sup>/L) during infection, significantly contributing to increased mortality risk (HR: 1.95, <em>p</em> = 0.008). Males exhibited a more pronounced impact. This study reveals heightened mortality risk in G6PD-deficient patients with diminished WBC counts during infections. Elevated CRP, globulins, and liver enzymes indicated severe infections, contrasting the unexpected non-response in WBC counts.</div></div><div><h3>Conclusion</h3><div>Vigilance in treating infections in G6PD-deficient patients, especially in males, is crucial for favorable outcomes. Diagnostic reliance on altered WBC counts in this population may misguide clinical decisions. G6PD deficiency poses a unique challenge in infection management, emphasizing the need for tailored interventions and exploration of alternative biomarkers for assessing severity and predicting mortality. Further studies and larger cohorts are essential for a comprehensive understanding and improved clinical practices.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"282 ","pages":"Article 110613"},"PeriodicalIF":3.8,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318096","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}
Pub Date : 2025-10-13DOI: 10.1016/j.clim.2025.110609
Emmanuel Ledoult , Thomas Guerrier , Sylvain Dubucquoi , Martin Figeac , Céline Villenet , Blanche Daunou , Helene Behal , Mohammad Ryadh Pokeerbux , Thomas Machet , Vincent Koether , Aurore Collet , David Launay , Lille Covid Research network (LICORNE)
COVID-19 induces a marked plasmablast (PB) expansion, whose functional role remains unclear. We performed B-cell immunophenotyping and multiplex cytokine analysis in a prospective cohort of 50 COVID-19 patients. PB expansion occurred early and correlated with both maximal disease severity and inflammatory markers. A retrospective cohort of 282 steroid-naïve patients was used to validate PB dynamics, model trajectories, and perform transcriptomic profiling. Two PB trajectories emerged: a transient one and a persistent, amplified one, the latter associated with a sixfold increase in 30-day mortality (p < 0.001). In severe cases, PB upregulated purine metabolism genes; in non-severe cases, they expressed interferon and CIITA-mediated MHC-II programs. BAFF levels at day 7 correlated with severity suggesting a role in sustaining PB expansion. PB exhibit functional duality in COVID-19—acting as immune regulators in non-severe cases and as inflammation amplifiers in severe disease. BAFF emerges as a potential therapeutic target in PB-driven immune dysregulation.
Trial registration.ClinicalTrials.govNCT04327180 and NCT04341792.
{"title":"Dual role of plasmablasts as immune regulators or amplifiers in COVID-19","authors":"Emmanuel Ledoult , Thomas Guerrier , Sylvain Dubucquoi , Martin Figeac , Céline Villenet , Blanche Daunou , Helene Behal , Mohammad Ryadh Pokeerbux , Thomas Machet , Vincent Koether , Aurore Collet , David Launay , Lille Covid Research network (LICORNE)","doi":"10.1016/j.clim.2025.110609","DOIUrl":"10.1016/j.clim.2025.110609","url":null,"abstract":"<div><div>COVID-19 induces a marked plasmablast (PB) expansion, whose functional role remains unclear. We performed B-cell immunophenotyping and multiplex cytokine analysis in a prospective cohort of 50 COVID-19 patients. PB expansion occurred early and correlated with both maximal disease severity and inflammatory markers. A retrospective cohort of 282 steroid-naïve patients was used to validate PB dynamics, model trajectories, and perform transcriptomic profiling. Two PB trajectories emerged: a transient one and a persistent, amplified one, the latter associated with a sixfold increase in 30-day mortality (<em>p</em> < 0.001). In severe cases, PB upregulated purine metabolism genes; in non-severe cases, they expressed interferon and CIITA-mediated MHC-II programs. BAFF levels at day 7 correlated with severity suggesting a role in sustaining PB expansion. PB exhibit functional duality in COVID-19—acting as immune regulators in non-severe cases and as inflammation amplifiers in severe disease. BAFF emerges as a potential therapeutic target in PB-driven immune dysregulation.</div><div><strong>Trial registration.</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> <span><span>NCT04327180</span><svg><path></path></svg></span> and <span><span>NCT04341792</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"281 ","pages":"Article 110609"},"PeriodicalIF":3.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298833","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}
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