Pub Date : 2024-12-18DOI: 10.1016/j.clicom.2024.12.003
Venkata Yeramilli , Michael Harper , Riadh Cheddadi , Colin Martin
Maternal stress is a risk factor for preterm birth and is associated with adverse birth outcomes and immune adaptations in the baby. In this study, we used a murine model of prenatal stress and measured serum immunoglobulin levels in the dams and offspring following stress. We found a significant decrease in the levels of all IgG subclasses in dams following stress. In contrast, we observed an increase in the levels of IgG1, IgG2b and IgG3 in the offspring derived from stressed dams compared to unstressed controls. We made similar observations in offspring that were fed corticosterone in drinking water during gestation indicating that these changes in immunoglobulin (Ig) levels are mediated by excess cortisol. Overall, the results from these studies will help better understand the casual link between prenatal maternal stress and compromised neonatal immunity and will help develop optimal vaccination strategies to protect both the pregnant women and infant.
{"title":"Maternal prenatal stress modulates antibody levels in offspring","authors":"Venkata Yeramilli , Michael Harper , Riadh Cheddadi , Colin Martin","doi":"10.1016/j.clicom.2024.12.003","DOIUrl":"10.1016/j.clicom.2024.12.003","url":null,"abstract":"<div><div>Maternal stress is a risk factor for preterm birth and is associated with adverse birth outcomes and immune adaptations in the baby. In this study, we used a murine model of prenatal stress and measured serum immunoglobulin levels in the dams and offspring following stress. We found a significant decrease in the levels of all IgG subclasses in dams following stress. In contrast, we observed an increase in the levels of IgG1, IgG2b and IgG3 in the offspring derived from stressed dams compared to unstressed controls. We made similar observations in offspring that were fed corticosterone in drinking water during gestation indicating that these changes in immunoglobulin (Ig) levels are mediated by excess cortisol. Overall, the results from these studies will help better understand the casual link between prenatal maternal stress and compromised neonatal immunity and will help develop optimal vaccination strategies to protect both the pregnant women and infant.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 27-33"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-15DOI: 10.1016/j.clicom.2024.12.002
Atsushi Iwai
β-glucans consisting of β-(1,3)-linked glucose as the main chain (hereafter simply called “β-glucan”) are suggested to have the potential for many beneficial effects on health. Among known beneficial effects, the most notable effect of β-glucan would be the antitumor effect. The antitumor effect of β-glucan has been known since the mid-twentieth century. In current cancer treatments where immune checkpoint inhibitors are attracting attention, it is expected that the combined administration of β-glucan will exhibit a greater therapeutic effect. The antitumor effect of β-glucan is believed to be closely linked to the receptors that recognize β-glucan. On the other hand, it has been clarified that there are many receptors for the recognition of β-glucan, in addition to CR3 (complement receptor 3) and dectin-1 (dendritic cell-associated C-type lectin-1), the well-known β-glucan receptors. This review focused on various β-glucan receptors reported previously and discusses the molecular mechanisms through which β-glucans exhibit antitumor effects.
{"title":"Involvement of β-glucan receptors on the antitumor activity of β-glucans","authors":"Atsushi Iwai","doi":"10.1016/j.clicom.2024.12.002","DOIUrl":"10.1016/j.clicom.2024.12.002","url":null,"abstract":"<div><div>β-glucans consisting of β-(1,3)-linked glucose as the main chain (hereafter simply called “β-glucan”) are suggested to have the potential for many beneficial effects on health. Among known beneficial effects, the most notable effect of β-glucan would be the antitumor effect. The antitumor effect of β-glucan has been known since the mid-twentieth century. In current cancer treatments where immune checkpoint inhibitors are attracting attention, it is expected that the combined administration of β-glucan will exhibit a greater therapeutic effect. The antitumor effect of β-glucan is believed to be closely linked to the receptors that recognize β-glucan. On the other hand, it has been clarified that there are many receptors for the recognition of β-glucan, in addition to CR3 (complement receptor 3) and dectin-1 (dendritic cell-associated C-type lectin-1), the well-known β-glucan receptors. This review focused on various β-glucan receptors reported previously and discusses the molecular mechanisms through which β-glucans exhibit antitumor effects.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 1-17"},"PeriodicalIF":0.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-13DOI: 10.1016/j.clicom.2024.12.001
José E Belizário
Diverse classes of antimicrobial peptides (AMPs) produced by keratinocytes, sebocytes, epithelial cells of apocrine and eccrine sweat glands and innate immune cells are continually released in the skin tissue layers. Together they exert the fine homeostatic control of the host immune cells-skin microbiome interactions, inhibiting bacterial overgrowth and skin barrier disruption. Under a variety of pathological conditions, up or down regulation of AMP expression can contribute to microbial diversity imbalance or dysbiosis, which can initiate or worsen the most common cutaneous diseases. This review updates on the roles of dermcidin, defensins, cathelicidins and S100 proteins as modulators of microbiomes, inflammation and recurrent bacterial infections in psoriasis, atopic dermatitis and hidradenitis suppurativa. The top most significant disease-immune signaling pathways mediated by the cytokines IL-1, TNF-α, IL-17, IL-23 and IL-33 are also reviewed. Current studies suggest that raising and lowering of host cell- and bacterial-derived AMPs may directly affect microbiome and immunity homeostasis at local body sites. Molecular genetics and microbiome studies should help us to investigate the bacterial species and AMPs synergistic or harmful interactions with causal gene variants, harnessing their potential clinical application in the journey of skin disease patients.
{"title":"Role of skin antimicrobial peptides in the pathogenesis of psoriasis, atopic dermatitis and hidradenitis suppurative: Highlights on dermcidin","authors":"José E Belizário","doi":"10.1016/j.clicom.2024.12.001","DOIUrl":"10.1016/j.clicom.2024.12.001","url":null,"abstract":"<div><div>Diverse classes of antimicrobial peptides (AMPs) produced by keratinocytes, sebocytes, epithelial cells of apocrine and eccrine sweat glands and innate immune cells are continually released in the skin tissue layers. Together they exert the fine homeostatic control of the host immune cells-skin microbiome interactions, inhibiting bacterial overgrowth and skin barrier disruption. Under a variety of pathological conditions, up or down regulation of AMP expression can contribute to microbial diversity imbalance or dysbiosis, which can initiate or worsen the most common cutaneous diseases. This review updates on the roles of dermcidin, defensins, cathelicidins and S100 proteins as modulators of microbiomes, inflammation and recurrent bacterial infections in psoriasis, atopic dermatitis and hidradenitis suppurativa. The top most significant disease-immune signaling pathways mediated by the cytokines IL-1, TNF-α, IL-17, IL-23 and IL-33 are also reviewed. Current studies suggest that raising and lowering of host cell- and bacterial-derived AMPs may directly affect microbiome and immunity homeostasis at local body sites. Molecular genetics and microbiome studies should help us to investigate the bacterial species and AMPs synergistic or harmful interactions with causal gene variants, harnessing their potential clinical application in the journey of skin disease patients.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 18-26"},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anti-type-I interferon (IFN) autoantibodies have been associated with severe COVID-19. Their association with long COVID, however, is unclear.
Anti-IFN-α2 antibody levels were followed-up for one year in individuals hospitalized for acute COVID-19 (n=97). Specific anti-IFN-α2 antibodies were detected in 5/97 patients. High anti-IFN-α2 antibody levels during acute infection were only detected in patients admitted to ICU (3/42), of whom 2 had persistent high levels and residual changes on chest computed tomography 12 months post-infection. Two patients not admitted to ICU had undetectable antibodies during acute infection, but had low detectable antibody levels 12 months post-infection; one of whom suffered from long COVID.
In conclusion, anti-IFN-α2 antibodies during acute infection are not associated with post-SARS-CoV-2 residual sequelae. Two patients with initially undetectable anti-IFN-α2 autoantibodies showed increased autoantibody levels 12 months post-infection. Additional large studies are needed to study the potential role of loss of tolerance after SARS-CoV-2 infection in long COVID.
{"title":"Long-term follow-up of anti-IFN-α2 autoantibody levels in hospitalized individuals with COVID-19","authors":"Maaike Cockx , Nick Geukens , Birthe Michiels , Doreen Dillaerts , Eveline Claeys , Olivia Vandekerckhove , Natalie Lorent , Xavier Bossuyt","doi":"10.1016/j.clicom.2024.11.001","DOIUrl":"10.1016/j.clicom.2024.11.001","url":null,"abstract":"<div><div>Anti-type-I interferon (IFN) autoantibodies have been associated with severe COVID-19. Their association with long COVID, however, is unclear.</div><div>Anti-IFN-α2 antibody levels were followed-up for one year in individuals hospitalized for acute COVID-19 (n=97). Specific anti-IFN-α2 antibodies were detected in 5/97 patients. High anti-IFN-α2 antibody levels during acute infection were only detected in patients admitted to ICU (3/42), of whom 2 had persistent high levels and residual changes on chest computed tomography 12 months post-infection. Two patients not admitted to ICU had undetectable antibodies during acute infection, but had low detectable antibody levels 12 months post-infection; one of whom suffered from long COVID.</div><div>In conclusion, anti-IFN-α2 antibodies during acute infection are not associated with post-SARS-CoV-2 residual sequelae. Two patients with initially undetectable anti-IFN-α2 autoantibodies showed increased autoantibody levels 12 months post-infection. Additional large studies are needed to study the potential role of loss of tolerance after SARS-CoV-2 infection in long COVID.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"6 ","pages":"Pages 26-30"},"PeriodicalIF":0.0,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142700055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.clicom.2024.10.002
Yohei Sato , Yamato Hanawa , Akihito Tsubota
Mutations in NF-κB-related molecules result in combined immunodeficiency characterized by recurrent infection. In this study, we aimed to investigate the association between mutations in NF-κB family members, RELA, RELB, and RELC, and regulatory T cell (Treg) function in humans. RELA, RELB, and RELC were knocked out using CRISPR/Cas9-mediated homologous recombination in CD4+/CD8+ T cells and Tregs isolated from healthy donors. The RELA, RELB, and RELC knockouts did not alter the phenotype or cytokine production profile of CD4+/CD8+ T cells or Jurkat cells. Similar to that observed in knockout mice, RELA or RELC knockout in MT-2 cells and freshly isolated Tregs reduced FOXP3 expression and the immune suppressive function of Tregs. Additionally, PD-L1 expression in effector T cells and Tregs decreased considerably following RELC knockdown. These findings demonstrated that the deletion of RELA or RELC resulted in the loss of Treg-like phenotype and function owing to the downregulation of FOXP3 expression.
{"title":"CRISPR/Cas9-mediated RELA and RELC knockout in human regulatory T cells abrogates FOXP3 expression and suppressive function","authors":"Yohei Sato , Yamato Hanawa , Akihito Tsubota","doi":"10.1016/j.clicom.2024.10.002","DOIUrl":"10.1016/j.clicom.2024.10.002","url":null,"abstract":"<div><div>Mutations in NF-κB-related molecules result in combined immunodeficiency characterized by recurrent infection. In this study, we aimed to investigate the association between mutations in NF-κB family members, RELA, RELB, and RELC, and regulatory T cell (Treg) function in humans. <em>RELA, RELB</em>, and <em>RELC</em> were knocked out using CRISPR/Cas9-mediated homologous recombination in CD4<sup>+</sup>/CD8<sup>+</sup> T cells and Tregs isolated from healthy donors. The <em>RELA, RELB</em>, and <em>RELC</em> knockouts did not alter the phenotype or cytokine production profile of CD4<sup>+</sup>/CD8<sup>+</sup> T cells or Jurkat cells. Similar to that observed in knockout mice, <em>RELA</em> or <em>RELC</em> knockout in MT-2 cells and freshly isolated Tregs reduced FOXP3 expression and the immune suppressive function of Tregs. Additionally, PD-L1 expression in effector T cells and Tregs decreased considerably following RELC knockdown. These findings demonstrated that the deletion of RELA or RELC resulted in the loss of Treg-like phenotype and function owing to the downregulation of FOXP3 expression.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"6 ","pages":"Pages 15-25"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-07DOI: 10.1016/j.clicom.2024.09.001
Spencer Fang , Joshua Pillai , Baharullah Mahin
Deficiency of Interleukin-1 receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory disease first reported in 2009. To date, 33 patients have been previously characterized and reported in literature. To the best of our knowledge, there have been no recent studies that have broadly evaluated recent advances in understanding of this challenging and life-threatening condition. Herein, we comprehensively reviewed the etiology and cytogenetic abnormalities of DIRA. We then investigated the current diagnostics used for identifying the variants of this disease. Furthermore, we report the demographics and characteristics broadly found in the current patient sample. Lastly, we discuss the treatments (antibiotics, corticosteroids, etc.) and the primary biologics (anakinra, canakinumab, adalimumab, and rilonacept) used in patients, along with current information on their clinical safety and efficacy. Overall, although further investigations are required for this disease, this review may be informative to clinicians treating and managing patients presenting with DIRA.
白细胞介素-1受体拮抗剂缺乏症（DIRA）是一种罕见的常染色体隐性自身炎症性疾病，于2009年首次报道。迄今为止，已有 33 例患者的特征被描述出来，并有文献报道。据我们所知，近期还没有任何研究广泛评估了对这种具有挑战性且危及生命的疾病的最新认识进展。在此，我们全面回顾了 DIRA 的病因和细胞遗传学异常。然后，我们研究了目前用于识别这种疾病变异体的诊断方法。此外，我们还报告了目前患者样本中广泛存在的人口统计学特征。最后，我们讨论了患者使用的治疗方法（抗生素、皮质类固醇等）和主要生物制剂（阿纳金拉、卡纳库单抗、阿达木单抗和利龙赛普），以及有关其临床安全性和有效性的最新信息。总之，尽管这种疾病还需要进一步的研究，但这篇综述可能会对治疗和管理DIRA患者的临床医生有所启发。
{"title":"Deficiency of interleukin-1 receptor antagonist: An updated review of the pathogenesis, clinical characteristics, and treatments","authors":"Spencer Fang , Joshua Pillai , Baharullah Mahin","doi":"10.1016/j.clicom.2024.09.001","DOIUrl":"10.1016/j.clicom.2024.09.001","url":null,"abstract":"<div><p>Deficiency of Interleukin-1 receptor antagonist (DIRA) is a rare autosomal recessive autoinflammatory disease first reported in 2009. To date, 33 patients have been previously characterized and reported in literature. To the best of our knowledge, there have been no recent studies that have broadly evaluated recent advances in understanding of this challenging and life-threatening condition. Herein, we comprehensively reviewed the etiology and cytogenetic abnormalities of DIRA. We then investigated the current diagnostics used for identifying the variants of this disease. Furthermore, we report the demographics and characteristics broadly found in the current patient sample. Lastly, we discuss the treatments (antibiotics, corticosteroids, etc.) and the primary biologics (anakinra, canakinumab, adalimumab, and rilonacept) used in patients, along with current information on their clinical safety and efficacy. Overall, although further investigations are required for this disease, this review may be informative to clinicians treating and managing patients presenting with DIRA.</p></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"6 ","pages":"Pages 9-14"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772613424000131/pdfft?md5=efd31efbf265a26f98baec737ce483c3&pid=1-s2.0-S2772613424000131-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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