Pub Date : 2025-12-01Epub Date: 2025-09-18DOI: 10.1016/j.clicom.2025.09.004
Vanessa Mylenna Florêncio de Carvalho , Bárbara de Oliveira Silva , Priscilla Stela Santana de Oliveira , Thacianna Barreto da Costa , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Michelly Cristiny Pereira , Maira Galdino da Rocha Pitta
Background
Although vaccines and treatments exist, new SARS-CoV-2 variants continue to emerge. An imbalance between apoptosis and autophagy may contribute to COVID-19 pathogenesis, leading to tissue damage and inflammation.
Objective
To investigate the role of cell death-related proteins during SARS-CoV-2 infection and their associations with clinical variables.
Methods
A total of 140 samples were analyzed (n = 73 infected, n = 67 uninfected). Gene expression of apoptotic and autophagic markers was evaluated by RT-qPCR in peripheral blood mononuclear cells. Caspase 3/7 activity was assessed using flow cytometry.
Results
Infected patients showed higher expression of CASPASE 3, BID (p < 0.05), and MAP1LC3 (p < 0.01). CASPASE 3 expression was higher in variant omicron, male sex, high viral load, and various clinical symptoms. Caspase 3/7 activity increased in CD4⁺ T and B cells of individuals infected with SARS-CoV-2.
Conclusions
Although our previous results with CASPASE 3 are promising and suggest that it may become a potential therapeutic target, additional studies are needed to confirm these hypotheses and evaluate potential intervention strategies.
{"title":"CASPASE-3 expression and activity in PBMCs associate with SARS-CoV-2 infection and clinical features","authors":"Vanessa Mylenna Florêncio de Carvalho , Bárbara de Oliveira Silva , Priscilla Stela Santana de Oliveira , Thacianna Barreto da Costa , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Michelly Cristiny Pereira , Maira Galdino da Rocha Pitta","doi":"10.1016/j.clicom.2025.09.004","DOIUrl":"10.1016/j.clicom.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Although vaccines and treatments exist, new SARS-CoV-2 variants continue to emerge. An imbalance between apoptosis and autophagy may contribute to COVID-19 pathogenesis, leading to tissue damage and inflammation.</div></div><div><h3>Objective</h3><div>To investigate the role of cell death-related proteins during SARS-CoV-2 infection and their associations with clinical variables.</div></div><div><h3>Methods</h3><div>A total of 140 samples were analyzed (<em>n</em> = 73 infected, <em>n</em> = 67 uninfected). Gene expression of apoptotic and autophagic markers was evaluated by RT-qPCR in peripheral blood mononuclear cells. Caspase 3/7 activity was assessed using flow cytometry.</div></div><div><h3>Results</h3><div>Infected patients showed higher expression of CASPASE 3, BID (<em>p</em> < 0.05), and MAP1LC3 (<em>p</em> < 0.01). CASPASE 3 expression was higher in variant omicron, male sex, high viral load, and various clinical symptoms. Caspase 3/7 activity increased in CD4⁺ T and B cells of individuals infected with SARS-CoV-2.</div></div><div><h3>Conclusions</h3><div>Although our previous results with CASPASE 3 are promising and suggest that it may become a potential therapeutic target, additional studies are needed to confirm these hypotheses and evaluate potential intervention strategies.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 81-89"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218944","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}
Pub Date : 2025-12-01Epub Date: 2025-09-09DOI: 10.1016/j.clicom.2025.09.002
Shadab Seraji , Kamran Balighi , Amir Hooshang Ehsani , Ala Ehsani , Hamidreza Mahmoudi , Maryam Daneshpazhooh , Pedram Noormohammadpour , Saman Al Zahawi , Zeinab Aryanian , Parvaneh Hatami
Background
Bullous pemphigoid is a subepidermal autoimmune blistering disease caused by auto-antibodies directed against specific components of the basement membrane molecules. It has been shown that T cell function and B cell survival depend on B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily. Its contribution to the formation of BP is yet unknown, though.
Aim
To measure the serum level of cytokines B cell activating factor (BAFF) and proliferation inducing ligand (APRIL), as well as BP180 and BP230 antibodies in patients with bullous pemphigoid before and after treatment.
Methods
New patients with a confirmed diagnosis of bullous pemphigoid from a tertiary care hospital were selected. After obtaining written consent, blood samples were taken according to the required standards, and the levels of the above indices were checked before and four months after treatment.
Results
This prospective case-control study recruited 32 patients with newly diagnosed BP and 24 healthy controls. Based on the obtained results, BAFF and APRIL levels were higher in the case group than the control group both before and after the treatment. Specifically, the changes in the BAFF index were statistically significant in both conditions: before treatment compared to controls (P = 0.001) and after treatment compared to controls (P = 0.015). Similarly, significant changes were observed in the APRIL index for the cases when comparing before treatment to controls (P < 0.001). Interestingly, those who have been treated with rituximab experienced a high level of BAFF even after treatment and in comparison with the healthy group but a decline in APRIL, BP180, and BP230.
Conclusions
The results of this study showed a decrease in APRIL, BP180, and BP230 indices in patients with Bullous pemphigoid after treatment in accordance with clinical improvement and remission. This study is one step forward in elaborating the role of BAFF and APRIL in the pathogenesis and monitoring of patients with BP.
{"title":"Profiling the serum cytokine B cell activating factor (BAFF),proliferation inducing ligand (APRIL), and BP180, BP230 antibodies in bullous pemphigoid patients before and after treatment: a prospective case-control study","authors":"Shadab Seraji , Kamran Balighi , Amir Hooshang Ehsani , Ala Ehsani , Hamidreza Mahmoudi , Maryam Daneshpazhooh , Pedram Noormohammadpour , Saman Al Zahawi , Zeinab Aryanian , Parvaneh Hatami","doi":"10.1016/j.clicom.2025.09.002","DOIUrl":"10.1016/j.clicom.2025.09.002","url":null,"abstract":"<div><h3>Background</h3><div>Bullous pemphigoid is a subepidermal autoimmune blistering disease caused by auto-antibodies directed against specific components of the basement membrane molecules. It has been shown that T cell function and B cell survival depend on B-cell activating factor (BAFF), a member of the tumor necrosis factor superfamily. Its contribution to the formation of BP is yet unknown, though.</div></div><div><h3>Aim</h3><div>To measure the serum level of cytokines B cell activating factor (BAFF) and proliferation inducing ligand (APRIL), as well as BP180 and BP230 antibodies in patients with bullous pemphigoid before and after treatment.</div></div><div><h3>Methods</h3><div>New patients with a confirmed diagnosis of bullous pemphigoid from a tertiary care hospital were selected. After obtaining written consent, blood samples were taken according to the required standards, and the levels of the above indices were checked before and four months after treatment.</div></div><div><h3>Results</h3><div>This prospective case-control study recruited 32 patients with newly diagnosed BP and 24 healthy controls. Based on the obtained results, BAFF and APRIL levels were higher in the case group than the control group both before and after the treatment. Specifically, the changes in the BAFF index were statistically significant in both conditions: before treatment compared to controls (<em>P</em> = 0.001) and after treatment compared to controls (<em>P</em> = 0.015). Similarly, significant changes were observed in the APRIL index for the cases when comparing before treatment to controls (<em>P</em> < 0.001). Interestingly, those who have been treated with rituximab experienced a high level of BAFF even after treatment and in comparison with the healthy group but a decline in APRIL, BP180, and BP230.</div></div><div><h3>Conclusions</h3><div>The results of this study showed a decrease in APRIL, BP180, and BP230 indices in patients with Bullous pemphigoid after treatment in accordance with clinical improvement and remission. This study is one step forward in elaborating the role of BAFF and APRIL in the pathogenesis and monitoring of patients with BP.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 75-80"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095120","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}
Pub Date : 2025-12-01Epub Date: 2025-06-28DOI: 10.1016/j.clicom.2025.06.003
Carolina Coradi , Beatriz Geovana Leite Vacario , Marina Rayciki Sotomayor , Victor Pereira da Silva , Gabriela Bonetti Bellandi , Luísa Cristina Fortuna da Silva , Carlos Frederico de Almeida , Carolina Panis
Research into paraneoplastic neurologic syndromes (PNS) has advanced significantly. This progress is reflected in the continuous refinement of diagnostic criteria and the introduction of novel antibodies for research purposes. Recently, there have been insights into the involvement of T cells in the pathophysiology of certain PNS, although many aspects of the underlying mechanisms remain to be fully understood. In breast cancer, there is emerging evidence linking drug treatments to the onset of PNS, and associated molecular mechanisms enrolling the immune system have been delineated. Here, we explore the evolving understanding of paraneoplastic neurologic syndrome development in breast cancer patients, emphasizing the immunological molecular pathways involved and the role of cytotoxic chemotherapy and immunotherapy in this context.
{"title":"Paraneoplastic neurologic syndromes in breast cancer: Immunological mechanisms and therapeutic insights","authors":"Carolina Coradi , Beatriz Geovana Leite Vacario , Marina Rayciki Sotomayor , Victor Pereira da Silva , Gabriela Bonetti Bellandi , Luísa Cristina Fortuna da Silva , Carlos Frederico de Almeida , Carolina Panis","doi":"10.1016/j.clicom.2025.06.003","DOIUrl":"10.1016/j.clicom.2025.06.003","url":null,"abstract":"<div><div>Research into paraneoplastic neurologic syndromes (PNS) has advanced significantly. This progress is reflected in the continuous refinement of diagnostic criteria and the introduction of novel antibodies for research purposes. Recently, there have been insights into the involvement of T cells in the pathophysiology of certain PNS, although many aspects of the underlying mechanisms remain to be fully understood. In breast cancer, there is emerging evidence linking drug treatments to the onset of PNS, and associated molecular mechanisms enrolling the immune system have been delineated. Here, we explore the evolving understanding of paraneoplastic neurologic syndrome development in breast cancer patients, emphasizing the immunological molecular pathways involved and the role of cytotoxic chemotherapy and immunotherapy in this context.</div></div>","PeriodicalId":100269,"journal":{"name":"Clinical Immunology Communications","volume":"8 ","pages":"Pages 26-37"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564050","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}
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 ACE2, TLR7, TLR8, TLR4, DDX58, and IFIH1 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.
{"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 , Adelina Yosifova , Atanas Syarov , Andrey Velichkov , Martin Pasev , Svetlomir Takov , Kalina Madarzhieva , Krassimir Angelov , Radoslava Vazharova , 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-05-13DOI: 10.1016/j.clicom.2025.05.002
Eduardo Davi Lima da Silva , Heloisa Isabela Leão , Ryan Cordeiro Silva , Nathália Tavares Ferreira , Amanda Pinheiro de Barros Albuquerque , André Machado de Siqueira , Michelly Cristiny Pereira , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , Maira Galdino da Rocha Pitta
Background
This study investigates Galectin-9 (Gal-9) as a potential biomarker for COVID-19 severity, aiming to improve patient stratification and guide clinical management.
Design and methods
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.
Results
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.
Conclusion
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.
{"title":"Gal-9: A potential game-changer in COVID-19 severity assessment","authors":"Eduardo Davi Lima da Silva , Heloisa Isabela Leão , Ryan Cordeiro Silva , Nathália Tavares Ferreira , Amanda Pinheiro de Barros Albuquerque , André Machado de Siqueira , Michelly Cristiny Pereira , Michelle Melgarejo da Rosa , Moacyr Jesus Barreto de Melo Rêgo , 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-02-28DOI: 10.1016/j.clicom.2025.02.002
Andrea Monjo , Tania Rodríguez-Ramos , Mark R. Bruder , Nguyen T.K. Vo , Mark Oremus , Kevin J. Stinson , Brian Dixon , Marc G Aucoin
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.
{"title":"Serological responses to SARS-CoV-2 in vaccinated and unvaccinated individuals: A Canadian study","authors":"Andrea Monjo , Tania Rodríguez-Ramos , Mark R. Bruder , Nguyen T.K. Vo , Mark Oremus , Kevin J. Stinson , Brian Dixon , 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-04-29DOI: 10.1016/j.clicom.2025.04.001
Susanna P.C. Höppener , Saskia R. Veldkamp , Mark C.H. de Groot , Saskia Haitjema , Julia Drylewicz , Jaap Jan Boelens , Caroline A. Lindemans , Joris van Montfrans , Annet van Royen-Kerkhof , Marc H.A. Jansen
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 <-2SD 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 (>6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic >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+B cells reconstituted in a median of 11 months (IQR=[7.3–18.0]), while CD19+CD27+IgG+ switched memory B cells took significantly longer, with a median of 1.8 years (IQR=[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.
{"title":"Persistent hypogammaglobulinemia after rituximab therapy in pediatric patients, prevalence and clinical outcomes","authors":"Susanna P.C. Höppener , Saskia R. Veldkamp , Mark C.H. de Groot , Saskia Haitjema , Julia Drylewicz , Jaap Jan Boelens , Caroline A. Lindemans , Joris van Montfrans , Annet van Royen-Kerkhof , 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 <-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 (>6 months) was observed in 46/91 patients (50.5 %), of whom 9 patients remained hypogammaglobulinemic >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<sup>+</sup> <em>B</em> cells reconstituted in a median of 11 months (<em>IQR</em>=[7.3–18.0]), while CD19<sup>+</sup>CD27<sup>+</sup>IgG<sup>+</sup> 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-01-09DOI: 10.1016/j.clicom.2025.01.001
Muhammad Adnan Zaman , Tahlyn Miller , Warsha Korani , Mina Jilani
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.
{"title":"Fever of unknown origin in a dialysis patient: A case report of dialyzer membrane allergy","authors":"Muhammad Adnan Zaman , Tahlyn Miller , Warsha Korani , 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":"2025-06-01","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}