Immunity & Ageing最新文献

{"title":"Distinct immunomodulation elicited by young versus aged extracellular vesicles in bone marrow-derived macrophages.","authors":"Dora Livkisa, Tsung-Lin Lee, Wei-Ting Yeh, Manuel S V Jaimes, Barbara Szomolay, Chia-Te Liao, David J Lundy","doi":"10.1186/s12979-024-00472-x","DOIUrl":"10.1186/s12979-024-00472-x","url":null,"abstract":"<p><strong>Background: </strong>Previous research has indicated that extracellular vesicles (EVs) potentially play significant roles in multiple ageing phenotypes. This study uses a factorial experimental design to explore the interactions between circulating EVs and bone marrow-derived macrophages (BMDMs) isolated from young (7-12 weeks) and aged (70-90 weeks) mice.</p><p><strong>Results: </strong>In this study, plasma EVs from young (Y_EV) and aged (O_EV) mice were isolated and compared based on abundance, size, and miRNA cargo. Compared to some previous studies, we found relatively few differences in EV miRNA cargo between Y_EVs and O_EVs. Young and old EVs were then used to stimulate naïve BMDMs isolated from young (Y_BMDM) and aged (O_BMDM) mice. A panel of five \"M1\" and six \"M2\" macrophage markers were used to assess the degree of polarisation. Our results revealed differences in the immunomodulatory effects of Y_EVs and O_EVs in Y_BMDMs and O_BMDMs. Y_EVs induced less pro-inflammatory gene expression, while O_EVs exhibited a more varied impact, promoting both pro- and anti-inflammatory markers. However, neither EV population induced a clearly defined 'M1' or 'M2' macrophage phenotype. We also report that EVs elicited responses that differed markedly from those induced by whole plasma. Plasma from old mice had strong pro-inflammatory effects on Y_BMDMs, increasing Il1b, Nlrp3 and Tnfa. However, O_EVs did not have these effects, supporting current evidence that EVs are a separate component of circulating factors during ageing. More research is needed to elucidate specific factors involved in inflammageing processes.</p><p><strong>Conclusions: </strong>Our findings reveal age-related differences in EV cargo and function, with young EVs tending to suppress inflammatory markers more effectively than aged EVs. However, this is not straightforward, and EVs often promoted both M1 and M2 markers. These results suggest that EVs are a distinct component of circulating factors and hold potential for therapeutic strategies aimed at mitigating age-related inflammation and immune dysregulation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"72"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480269","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":"Inhibiting IL11: a novel approach to turning back the clock.","authors":"Osama Ahmad, Muhammad Haris","doi":"10.1186/s12979-024-00477-6","DOIUrl":"10.1186/s12979-024-00477-6","url":null,"abstract":"<p><p>The World Health Organization recognizes frailty and multimorbidity as major global health issues and underscores the need for effective interventions. Recent advances have identified interleukin-11 (IL-11), a pro-inflammatory cytokine, as a key player in modulating aging pathways (such as ERK, AMPK, mTOR and JAK-STAT3). Studies have shown that IL-11 inhibition can lead to improved health span and lifespan in animal models, with potential applications in humans. By targeting IL-11, researchers aim to mitigate age-related diseases, such as cancer, fibrosis, and multimorbidity, which pose significant healthcare challenges worldwide. IL-11 inhibition offers a promising strategy, with preclinical trials demonstrating its ability to regenerate renal cells, reduce hepatocyte death, and mitigate liver fibrosis. Further research is necessary to fully elucidate the mechanisms of IL-11 inhibition and its therapeutic potential. If successful, this approach could lead to the development of novel pharmacological interventions, promoting healthier aging and increasing human lifespan.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"71"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480271","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":"Association between serum IgM and all-cause mortality risk in Chinese centenarians: a prospective cohort study.","authors":"Weiguang Zhang, Yuting Duan, Zhe Li, Yue Niu, Bin Wang, Zhe Feng, Ding Sun, Hao Li, Zehao Zhang, Zeyu Qu, Miao Liu, Hongyan Hu, Qiao Zhu, Yujian Chen, Chaoxue Ning, Shihui Fu, Shanshan Yang, Shengshu Wang, Yali Zhao, Yao He, Xiangmei Chen, Yizhi Chen","doi":"10.1186/s12979-024-00475-8","DOIUrl":"https://doi.org/10.1186/s12979-024-00475-8","url":null,"abstract":"<p><strong>Background: </strong>We investigated the associations between IgM, IgG, IgA, and IgE levels and all-cause mortality risk in Chinese centenarians.</p><p><strong>Methods: </strong>All participants were from the China Hainan Centenarian Cohort Study. Eligible participants were divided into quartiles based on their IgM, IgG, IgA, and IgE levels. We used restricted cubic spline analyses, Cox regression analyses, and Kaplan-Meier survival curves to analyze associations between IgM, IgG, IgA, and IgE and all-cause mortality risk.</p><p><strong>Results: </strong>A total of 906 centenarian participants were included in this study (81.2% female; median age, 102 years). During a median follow-up of 30.1 months, 838 (92.5%) participants died. Restricted cubic spline analysis revealed a nonlinear relationship (\"L\" type) between serum IgM level and all-cause mortality. Compared with the higher three quartiles of serum IgM level, the lowest quartile was associated with a higher risk of death (Q1 versus Q2-Q4: HR, 1.365; 95% CI, 1.166-1.598; P < 0.001). Among individuals for whom IgM < 0.708 g/L (Q1), the risk of all-cause mortality was 36.5% higher. Kaplan-Meier analyses showed that centenarians with lower serum IgM levels had significantly shorter median survival time (Q1 versus Q2-Q4: 26 months versus 32 months, log-rank P = 0.001).</p><p><strong>Conclusion: </strong>Serum IgM levels in centenarians significantly correlated with the risk of death, suggesting that they are suitable for predicting the overall risk of death in centenarians and can be used as an independent predictor of death.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"70"},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480268","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":"Health characteristics associated with persistence of SARS-CoV-2 antibody responses after repeated vaccinations in older persons over time: the Doetinchem cohort study.","authors":"Yunus Kuijpers, Joanna Kaczorowska, H Susan J Picavet, Mary-Lène de Zeeuw-Brouwer, Marjan Kuijer, Irene Slits, Esther Gijsbers, Ryanne Rutkens, Lia de Rond, W M Monique Verschuren, Anne-Marie Buisman","doi":"10.1186/s12979-024-00476-7","DOIUrl":"https://doi.org/10.1186/s12979-024-00476-7","url":null,"abstract":"<p><strong>Background: </strong>Older persons elicit heterogeneous antibody responses to vaccinations that generally are lower than those in younger, healthier individuals. As older age and certain comorbidities can influence these responses we aimed to identify health-related variables associated with antibody responses after repeated SARS-CoV-2 vaccinations and their persistence thereafter in SARS-CoV-2 infection-naïve and previously infected older persons.</p><p><strong>Method: </strong>In a large longitudinal study of older persons of the general population 50 years and over, a sub-cohort of the longitudinal Doetinchem cohort study (n = 1374), we measured IgG antibody concentrations in serum to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N). Samples were taken following primary vaccination with BNT162b2 or AZD1222, pre- and post-vaccination with a third and fourth BNT162b2 or mRNA-1273 (Wuhan), and up to a year after a fifth BNT162b2 bivalent (Wuhan/Omicron BA.1) vaccine. Associations between persistence of antibody concentrations over time and age, sex, health characteristics including cardiometabolic and inflammatory diseases as well as a frailty index were tested using univariable and multivariable models.</p><p><strong>Results: </strong>The booster doses substantially increased anti-SARS-CoV-2 Spike S1 (S1) antibody concentrations in older persons against both the Wuhan and Omicron strains. Older age was associated with decreased antibody persistence both after the primary vaccination series and up to 1 year after the fifth vaccine dose. In infection-naïve persons the presence of inflammatory diseases was associated with an increased antibody response to the third vaccine dose (Beta = 1.53) but was also associated with reduced persistence over the 12 months following the fifth (bivalent) vaccine dose (Beta = -1.7). The presence of cardiometabolic disease was associated with reduced antibody persistence following the primary vaccination series (Beta = -1.11), but this was no longer observed after bivalent vaccination.</p><p><strong>Conclusion: </strong>Although older persons with comorbidities such as inflammatory and cardiometabolic diseases responded well to SARS-CoV-2 booster vaccinations, they showed a reduced persistence of these responses. This might indicate that especially these more vulnerable older persons could benefit from repeated booster vaccinations.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"68"},"PeriodicalIF":5.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480270","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":"Quercetin ameliorates lupus symptoms by promoting the apoptosis of senescent Tfh cells via the Bcl-2 pathway.","authors":"Feng Xiong, Kai Shen, Di Long, Suqing Zhou, Pinglang Ruan, Yue Xin, Yuezheng Xiao, Weijun Peng, Ming Yang, Haijing Wu, Qianjin Lu","doi":"10.1186/s12979-024-00474-9","DOIUrl":"https://doi.org/10.1186/s12979-024-00474-9","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4⁺ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4⁺ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"69"},"PeriodicalIF":5.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480272","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":"Inflammation scores based on C-reactive protein and albumin predict mortality in hospitalized older patients independent of the admission diagnosis.","authors":"Mirko Di Rosa, Jacopo Sabbatinelli, Angelica Giuliani, Miriam Carella, Daniele Magro, Leonardo Biscetti, Luca Soraci, Francesco Spannella, Massimiliano Fedecostante, Federica Lenci, Elena Tortato, Lorenzo Pimpini, Maurizio Burattini, Sara Cecchini, Antonio Cherubini, Anna Rita Bonfigli, Maria Capalbo, Antonio Domenico Procopio, Carmela Rita Balistreri, Fabiola Olivieri","doi":"10.1186/s12979-024-00471-y","DOIUrl":"10.1186/s12979-024-00471-y","url":null,"abstract":"<p><p>Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"67"},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Melatonin enhances NK cell function in aged mice by increasing T-bet expression via the JAK3-STAT5 signaling pathway.","authors":"Caiying Liang, Rongrong Song, Jieyu Zhang, Jie Yao, Ziyun Guan, Xiaokang Zeng","doi":"10.1186/s12979-024-00470-z","DOIUrl":"10.1186/s12979-024-00470-z","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"66"},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362421","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":"Monocyte-driven inflamm-aging reduces intestinal barrier function in females.","authors":"Candice Quin, Jessica A Breznik, Allison E Kennedy, Erica N DeJong, Catherine M Andary, Sofya Ermolina, Donald J Davidson, Jinhui Ma, Michael G Surette, Dawn M E Bowdish","doi":"10.1186/s12979-024-00469-6","DOIUrl":"10.1186/s12979-024-00469-6","url":null,"abstract":"<p><strong>Background: </strong>The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans. In addition, despite being well-established that biological sex impacts aging physiology, its influence on intestinal barrier function and inflamm-aging has not been explored.</p><p><strong>Results: </strong>In this study, we observed sex differences in markers of intestinal barrier integrity, where females had increased epithelial permeability throughout life as compared to males. With age, females had an age-associated increase in circulating bacterial products and metabolites such as LPS and kynurenine, suggesting reduced barrier function. Females also had age-associated increases in established markers of inflamm-aging, including peripheral blood monocytes as well as TNF and CRP. To determine if impaired barrier function was driving inflamm-aging, we performed a mediation analysis. The results show that the loss of intestinal barrier integrity was not the mediator of inflamm-aging in humans. Instead, persistent, low-grade inflammation with age preceded the increase in circulating bacterial products, which we confirmed using animal models. We found, as in humans, that sex modified age-associated increases in circulating monocytes in mice, and that inflammation mediates the loss of intestinal barrier function.</p><p><strong>Conclusion: </strong>Taken together, our results suggest that higher basal intestinal permeability in combination with age-associated inflammation, increases circulating LPS in females. Thus, targeting barrier permeability in females may slow the progression of inflamm-aging, but is unlikely to prevent it.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"65"},"PeriodicalIF":5.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332026","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":"Association of adipose tissue inflammation and physical fitness in older adults.","authors":"Anna Tylutka, Barbara Morawin, Natalia Torz, Joanna Osmólska, Kacper Łuszczki, Paweł Jarmużek, Agnieszka Zembron-Lacny","doi":"10.1186/s12979-024-00468-7","DOIUrl":"https://doi.org/10.1186/s12979-024-00468-7","url":null,"abstract":"<p><p>An active lifestyle is of key importance for reduction of obesity and inflammation, as well as circulating levels of adipokines. Therefore, the aim of our study was to assess the relationship of physical fitness with chronic inflammatory status, and to evaluate biomarkers useful in the analysis of adipose tissue dysfunction. Sixty-three older adults (69.6 ± 5.1 years) were allocated to a high n = 31 (women n = 23 and men n = 8 male) or low physical fitness n = 32 (women n = 29 and men n = 3) group based on gait speed values (1.4-1.8 m/s or ≤ 1.3 m/s). The gait speed correlated with hand grip strength (r_s = 0.493, p = 0.0001) and with leptin level (R = -0.372, p = 0.003), which shows the benefits of physical activity on muscle strength and circulating adipokines. In low physical fitness group, 58.1% individuals had adiponectin to leptin ratio (Adpn/Lep) < 0.5 revealing dysfunction of adipose tissue and high cardiometabolic risk; 20% of the group were obese with BMI ≥ 30 kg/m². In high physical fitness group, 25.8% of individuals had Adpn/Lep ≥ 1.0 i.e., within the reference range. Markers of systemic inflammation were significantly related to physical fitness: CRP/gait speed (r_s = -0.377) and HMGB-1/gait speed (r_s = -0.264). The results of the ROC analysis for Adpn (AUC = 0.526), Lep (AUC = 0.745) and HMGB-1 (AUC = 0.689) indicated their diagnostic potential for clinical prognosis in older patients. The optimal threshold values corresponded to 1.2 μg/mL for Adpn (sensitivity 74.2%, specificity 41.9%, OR = 1.4, 95%Cl 0.488-3.902), 6.7 ng/mL for Lep (sensitivity 56.2%, specificity 93.5%, OR = 14.8, 95%Cl 3.574-112.229), 2.63 mg/L for CRP (sensitivity 51.6%, specificity 84.3%, OR = 4.4, 95% Cl 1.401- 16.063) and 34.2 ng/mL for HMGB-1 (sensitivity 62.0%, specificity 86.6%, OR = 12.0, 95%Cl 3.254-61.614). The highest sensitivity and specificity were observed for Leptin and HMGB-1. The study revealed changes in inflammatory status in older adults at various levels of physical fitness and demonstrated diagnostic usefulness of adipokines in the assessment of adipose tissue inflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"64"},"PeriodicalIF":5.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332025","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":"Repeated COVID-19 mRNA vaccination results in IgG4 class switching and decreased NK cell activation by S1-specific antibodies in older adults","authors":"Anne T. Gelderloos, Marije K. Verheul, Irene Middelhof, Mary-Lène de Zeeuw-Brouwer, Robert S. van Binnendijk, Anne-Marie Buisman, Puck B. van Kasteren","doi":"10.1186/s12979-024-00466-9","DOIUrl":"https://doi.org/10.1186/s12979-024-00466-9","url":null,"abstract":"Previous research has shown that repeated COVID-19 mRNA vaccination leads to a marked increase of SARS-CoV-2 spike-specific serum antibodies of the IgG4 subclass, indicating far-reaching immunoglobulin class switching after booster immunization. Considering that repeated vaccination has been recommended especially for older adults, the aim of this study was to investigate IgG subclass responses in the ageing population and assess their relation with Fc-mediated antibody effector functionality. Spike S1-specific IgG subclass concentrations (expressed in arbitrary units per mL), antibody-dependent NK cell activation, complement deposition and monocyte phagocytosis were quantified in serum from older adults (n = 38–50, 65–83 years) at one month post-second, -third and -fifth vaccination. Subclass distribution in serum was compared to that in younger adults (n = 64, 18–47 years) at one month post-second and -third vaccination. Compared to younger individuals, older adults showed increased levels of IgG2 and IgG4 at one month post-third vaccination (possibly related to factors other than age) and a further increase following a fifth dose. The capacity of specific serum antibodies to mediate NK cell activation and complement deposition relative to S1-specific total IgG concentrations decreased upon repeated vaccination. This decrease associated with an increased IgG4/IgG1 ratio. In conclusion, these findings show that, like younger individuals, older adults produce antibodies with reduced functional capacity upon repeated COVID-19 mRNA vaccination. Additional research is needed to better understand the mechanisms underlying these responses and their potential implications for vaccine effectiveness. Such knowledge is vital for the future design of optimal vaccination strategies in the ageing population.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"19 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259694","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}