Clinical Immunology Communications最新文献

{"title":"The role of the T helper 17 and T regulatory cell ratio in the gut-thyroid axis","authors":"Julia Williams,&nbsp;Anna Gruvstad Melén,&nbsp;Michelle Barrow","doi":"10.1016/j.clicom.2025.06.002","DOIUrl":"10.1016/j.clicom.2025.06.002","url":null,"abstract":"<div><div>Alterations to the gut microbiota (GM) and its metabolites have been associated with Hashimoto’s Thyroiditis (HT) via modulation of T helper 17 (Th17) and T regulatory (Treg) cells. However, in comparison to other autoimmune diseases there is a shortfall in research investigating pathophysiological mechanisms. The aim of this review was to evaluate mechanisms linking the GM to the immune modulation of Th17 and Tregs in the context of HT.</div><div>A systematic literature search was undertaken in two tranches: 1) review papers; 2) primary human, animal and <em>in vitro</em> evidence. 80 papers met the inclusion criteria. Primary papers were critically appraised using SIGN50 and ARRIVE guidelines. Narrative analysis of the key mechanistic themes from primary studies was conducted and a network diagram was developed.</div><div>Th17 has a pathogenic phenotype but the context by which this conversion occurs is less well understood. Results suggested microbiota induced production of interleukin-6, interleukin-23 and serum amyloid A proteins play a role. However, downregulation of Tregs could be a prerequisite given their role in T effector cell suppression. Short-chain fatty acids may promote Treg activity; therefore, reduced levels could create a pathogenic environment. Translocation of lipopolysaccharides was indicated as a potential inducer of Th17. Evidence to support the migration of T cells primed in the intestines to other tissues also provided plausibility for mechanisms involving the gut-thyroid axis.</div><div>The findings suggest that the GM and its metabolites have immunomodulatory effects on the Th17/Treg ratio. However, research is lacking in HT patients and experimental thyroiditis animal models.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 10-25"},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DOCK8 deficiency patient presenting with purpura fulminans caused by group A β-hemolytic Streptococcus sepsis","authors":"Abduarahman Almutairi ,&nbsp;Nouf Althubaiti ,&nbsp;Khaled Abuneim ,&nbsp;Ghaziaa Alanezi ,&nbsp;Abdullah Alamer ,&nbsp;Imad A El Hag ,&nbsp;Fayhan J Alroqi ,&nbsp;Abdulrahman Alrasheed ,&nbsp;Waleed Al Maneea","doi":"10.1016/j.clicom.2025.06.001","DOIUrl":"10.1016/j.clicom.2025.06.001","url":null,"abstract":"<div><div>We report a male infant presenting with Purpura fulminans (PF) secondary to sepsis caused by group A β-hemolytic Streptococcus (GAS) associated with hyper-IgE syndrome due to deletion mutation in <em>DOCK8</em>. The patient, previously healthy, presented with clinical symptoms of fever, lethargy, hypotension with blood culture confirming GAS infection. Subsequently, he developed purpuric skin lesions on his extremities which progressed to gangrene necessitating amputation of his fingers and toes. The findings underscore the importance of considering inborn error of immunity, especially DOCK8 deficiency, in cases of infant presenting with acute infectious PF.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 6-9"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of CD38brightHLA-DR+ T cells using a rapid flow cytometry-based assay to aid in the diagnosis of hemophagocytic lymphohistiocytosis and immune regulatory disorders in adult subjects","authors":"Aaruni Khanolkar,&nbsp;Erin Weyers,&nbsp;Ramakrishna Sompallae,&nbsp;Matthew D. Krasowski","doi":"10.1016/j.clicom.2025.05.004","DOIUrl":"10.1016/j.clicom.2025.05.004","url":null,"abstract":"<div><div>Rapid and accurate diagnosis of patients suspected of suffering from hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH) is a critical aspect of timely management for such disorders. Soluble IL-2Rα (sIL-2Rα) and plasma ferritin constitute the mainstay of frontline laboratory investigations performed to establish a clinical diagnosis for these patients. However, there is a paucity of clinical laboratories that perform the sIL-2Rα measurement as a <em>stat</em> test which can delay the diagnosis and management of these patients. Consequently, rapid flow cytometry-based tests that measure T cell activation are currently being evaluated. Previous studies have examined the utility of flow-cytometry based testing in pediatric subjects with HLH and immune dysregulation disorders. In this report, we assessed the utility of our flow-cytometry based test in adult patients suspected of HLH and discuss its performance in relation to what has been reported previously in the literature for pediatric patients.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 1-5"},"PeriodicalIF":0.0,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and significance of anti-citrullinated cyclic peptide antibodies in relapsing polychondritis","authors":"Damien Sène ,&nbsp;Sophie Hue ,&nbsp;Pascale Ghillani-Dalbin ,&nbsp;Sophie Caillat-Zucman ,&nbsp;Jean-Charles Piette","doi":"10.1016/j.clicom.2025.05.003","DOIUrl":"10.1016/j.clicom.2025.05.003","url":null,"abstract":"","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 79-81"},"PeriodicalIF":0.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gal-9: A potential game-changer in COVID-19 severity assessment","authors":"Eduardo Davi Lima da Silva ,&nbsp;Heloisa Isabela Leão ,&nbsp;Ryan Cordeiro Silva ,&nbsp;Nathália Tavares Ferreira ,&nbsp;Amanda Pinheiro de Barros Albuquerque ,&nbsp;André Machado de Siqueira ,&nbsp;Michelly Cristiny Pereira ,&nbsp;Michelle Melgarejo da Rosa ,&nbsp;Moacyr Jesus Barreto de Melo Rêgo ,&nbsp;Maira Galdino da Rocha Pitta","doi":"10.1016/j.clicom.2025.05.002","DOIUrl":"10.1016/j.clicom.2025.05.002","url":null,"abstract":"<div><h3>Background</h3><div>This study investigates Galectin-9 (Gal-9) as a potential biomarker for COVID-19 severity, aiming to improve patient stratification and guide clinical management.</div></div><div><h3>Design and methods</h3><div>We analyzed Gal-9 levels (blood and saliva) in 112 mild, 57 severe COVID-19 patients, 93 symptomatic non-COVID-19 individuals, and 70 controls (healthy controls) using ELISA and RT-qPCR.</div></div><div><h3>Results</h3><div>Both mild and severe COVID-19 patients exhibited elevated Galectin-9 (Gal-9) levels, with severe cases showing significantly higher serum levels (mRNA and protein) compared to mild or healthy controls. This suggests Galectin-9 involvement in the acute phase, as levels declined within 15 days post-diagnosis. Fever and cough correlated with disease severity. ROC analysis demonstrated high accuracy in patient stratification. Furthermore, we detected elevated Galectin-9 protein in the saliva of individuals with mild COVID-19, highlighting its potential as a non-invasive biomarker for early disease detection.</div></div><div><h3>Conclusion</h3><div>This study identifies Gal-9 as a promising biomarker for COVID-19 severity. Elevated Gal-9 levels hold potential for improved patient stratification and clinical management, highlighting the importance of biomarker research in understanding COVID-19 pathophysiology.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 64-71"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of the interleukin-1 receptor antagonist: Characterizing the molecular consequences of loss-of-function IL1RN variants from structural and biochemical evidence","authors":"Joshua Pillai ,&nbsp;Spencer Fang","doi":"10.1016/j.clicom.2025.05.001","DOIUrl":"10.1016/j.clicom.2025.05.001","url":null,"abstract":"<div><div>Deficiency of interleukin-1 receptor antagonist (DIRA) is a rare autoinflammatory disease with neonatal onset defined by periostitis, pustulosis, and sterile osteomyelitis. DIRA is caused by biallelic loss-of-function mutations in the <em>IL1RN</em> gene, including 16 cytogenetic abnormalities to date. Due to the rarity of the condition, limited studies have evaluated the molecular basis and consequences of pathogenic <em>IL1RN</em> variants. Herein, we reviewed structural data from the crystal structure of IL-1Ra/IL-1R1 complex along with complementary experimental evidence from prior studies to characterize impacts on protein folding and binding affinity to IL-1R1. Furthermore, we define the hypomorphic R26X variant and suggest that genomic distance influences the ability of translation reinitiation in the context of DIRA, as another variant in the N-terminal did not undergo the same mechanism. Lastly, we provide a multiple-sequence alignment and structural template to better streamline analyses and reporting of novel <em>IL1RN</em> variants in the near future.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 72-78"},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes","authors":"Susanna P.C. Höppener ,&nbsp;Saskia R. Veldkamp ,&nbsp;Mark C.H. de Groot ,&nbsp;Saskia Haitjema ,&nbsp;Julia Drylewicz ,&nbsp;Jaap Jan Boelens ,&nbsp;Caroline A. Lindemans ,&nbsp;Joris van Montfrans ,&nbsp;Annet van Royen-Kerkhof ,&nbsp;Marc H.A. Jansen","doi":"10.1016/j.clicom.2025.04.001","DOIUrl":"10.1016/j.clicom.2025.04.001","url":null,"abstract":"<div><div>Hypogammaglobulinemia is a known side effect of rituximab (RTX) in adults, but its prevalence and persistence in children remain underexplored. This retrospective cohort study at a tertiary care center examines the prevalence and clinical outcomes of hypogammaglobulinemia in pediatric patients after RTX therapy. Patients aged ≤ 18 years treated with RTX for various indications between 2000 and 2020 were included. Patients were classified as having hypogammaglobulinemia when (1) IgG levels were &lt;-2<em>SD</em> below reference for age, or (2) when they received immunoglobulin replacement therapy (IGRT) for the indication hypogammaglobulinemia. Hypogammaglobulinemia after RTX treatment was observed in 74/134 patients (55.2 %). Persistent hypogammaglobulinemia (&gt;6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic &gt;5 years. Low baseline IgG and IgM levels were significantly associated with persistent hypogammaglobulinemia, while patients receiving RTX therapy for autoimmune diseases were less frequently affected. CD19⁺ <em>B</em> cells reconstituted in a median of 11 months (<em>IQR</em>=[7.3–18.0]), while CD19⁺CD27⁺IgG⁺ switched memory B cells took significantly longer, with a median of 1.8 years (<em>IQR</em>=[1.0–2.9]). Three patients developed class-switch recombination-deficiencies and never recovered. Recurrent infections, of which two fatal, were recorded in 18 patients and were significantly more prevalent in those with persistent hypogammaglobulinemia. In conclusion, over half of children had low IgG levels and/or required IGRT for hypogammaglobulinemia following RTX therapy. Persistent hypogammaglobulinemia was associated with low pre-RTX IgG and/or IgM levels. Children with hypogammaglobulinemia after RTX are often IGRT-dependent, experience recurrent (and sometimes fatal) infections, and may develop secondary immunoglobulin class-switch defects.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 55-63"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143943645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expansion of SARS-CoV-2 mutations in patient with B-cell lymphoma and rare combination of ACE2, TLR4, DDX58 and IFIH1 variations: A retrospective analysis of the virus-host interplay","authors":"Angelina Trifonova ,&nbsp;Adelina Yosifova ,&nbsp;Atanas Syarov ,&nbsp;Andrey Velichkov ,&nbsp;Martin Pasev ,&nbsp;Svetlomir Takov ,&nbsp;Kalina Madarzhieva ,&nbsp;Krassimir Angelov ,&nbsp;Radoslava Vazharova ,&nbsp;Velislava Terzieva","doi":"10.1016/j.clicom.2025.02.001","DOIUrl":"10.1016/j.clicom.2025.02.001","url":null,"abstract":"<div><div>Lessons from the COVID-19 outbreak suggest a highly variable individual clinical course of infection and unpredictable outcomes among infected individuals. In this retrospective study, we examined the intra-host viral evolution in an immunocompromised patient with B-cell lymphoma, severe COVID-19, and a two-stage, long-lasting in-hospital period with lethal outcome. The whole-genome sequencing profile demonstrated a dynamic accumulation of new viral mutations in the entire viral genome, mainly in S1-RBD and Nsp12, against the background of antiviral treatment and convalescent plasma transfusion. Long range-PCR and nanopore sequencing of <em>ACE2, TLR7, TLR8, TLR4, DDX58,</em> and <em>IFIH1</em> genes revealed single nucleotide substitutions in the ACE2, TLR4, DDX58, IFIH1, and TLR7 receptors, negatively affecting the disease course from the onset. Our results demonstrate that genetic variations in host innate immunity and impaired adaptive immunity facilitate the accumulation of viral mutations that overcome antiviral treatment and passive antibody transfer, affecting the course of SARS-CoV-2 infection.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 47-54"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577284","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}

{"title":"Serological responses to SARS-CoV-2 in vaccinated and unvaccinated individuals: A Canadian study","authors":"Andrea Monjo ,&nbsp;Tania Rodríguez-Ramos ,&nbsp;Mark R. Bruder ,&nbsp;Nguyen T.K. Vo ,&nbsp;Mark Oremus ,&nbsp;Kevin J. Stinson ,&nbsp;Brian Dixon ,&nbsp;Marc G Aucoin","doi":"10.1016/j.clicom.2025.02.002","DOIUrl":"10.1016/j.clicom.2025.02.002","url":null,"abstract":"<div><div>COVID-19 severity has been correlated with older age, male sex, and the presence of comorbidities; it is hypothesized that SARS-CoV-2 antibody responses are also correlated.159 unvaccinated patients with SARS-CoV-2 infections were assessed for IgA, IgG, and IgM titers, which were compared with disease severity, age, sex, presence of comorbidities, and time since infection. Anti-S and anti-Nucleocapsid (N) IgG responses were compared between unvaccinated and vaccinated SARS-CoV-2 positive patients. Anti-S IgA and IgM were better indicators of disease severity than IgG. IgG responses were more likely for patients over 60 years old. Female patients over 60 were more likely to have an antibody response than female patients under 60. Vaccinated patients had a stronger IgG response against S protein than against N protein likely due to immune imprinting. Disease severity was correlated with anti-S antibody responses and comorbidities in unvaccinated patients.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 39-46"},"PeriodicalIF":0.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549428","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}

{"title":"Fever of unknown origin in a dialysis patient: A case report of dialyzer membrane allergy","authors":"Muhammad Adnan Zaman ,&nbsp;Tahlyn Miller ,&nbsp;Warsha Korani ,&nbsp;Mina Jilani","doi":"10.1016/j.clicom.2025.01.001","DOIUrl":"10.1016/j.clicom.2025.01.001","url":null,"abstract":"<div><div>Fever following hemodialysis presents a diagnostic challenge, often raising concerns about infection. However, non-infectious causes, such as allergic reactions to dialysis membranes, must also be considered. Dialyzer-related reactions, particularly to synthetic membranes like polysulfone, are increasingly recognized as contributors to post-dialysis fever. Although modern dialysis technology has improved biocompatibility by eliminating acetate buffers and sterilizing ethylene oxide, acute hypersensitivity reactions still occur. These reactions are classified into Type A (anaphylactic) and Type B (non-anaphylactic), each with distinct symptoms. Proper identification of these reactions is essential for management, as switching to a more biocompatible membrane is often required. This case report describes a 38-year-old male who developed a fever after hemodialysis in a prison facility. Initial workup ruled out infection, with negative blood cultures and elevated IgE levels suggesting a hypersensitivity reaction to the polysulfone membrane. The patient's symptoms resolved following a switch to a hypoallergenic dialyzer.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"7 ","pages":"Pages 34-38"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143167299","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}