Challenges for gene editing in common variable immunodeficiency disorders: Current and future prospects
Clin Immunol. 2023 Nov 25:109854. doi: 10.1016/j.clim.2023.109854. Online ahead of print.ABSTRACTThe original CRISPR Cas9 gene editing system and subsequent innovations offers unprecedented opportunities to correct severe genetic defects including those causing Primary Immunodeficiencies (PIDs). Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic PID in adults and children. Unlike many other PIDs, patients meeting CVID criteria do not have a definable genetic defect and cannot be considered to have an inborn error of immunity (IEI). Patients with a CVID phenotype carrying a causative mutatio...
Source: Clinical Immunology - November 28, 2023 Category: Allergy & Immunology Authors: Rohan Ameratunga Euphemia Leung See-Tarn Woon Edward Lea Caroline Allan Lydia Chan Hilary Longhurst Richard Steele Russell Snell Klaus Lehnert Source Type: research
Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis
In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic ...
Source: Clinical Immunology - November 28, 2023 Category: Allergy & Immunology Authors: Yaoyu Pu Ruijuan Cheng Qiuping Zhang Tianwen Huang Chenyang Lu Zhigang Tang Yutong Zhong Liang Wu Bruce D Hammock Kenji Hashimoto Yubin Luo Yi Liu Source Type: research
Changes in mucosal IgG4 < sup > + < /sup > - and IL-10 < sup > + < /sup > -cell frequencies in adults with eosinophilic esophagitis on a two-food elimination diet
Clin Immunol. 2023 Nov 25:109853. doi: 10.1016/j.clim.2023.109853. Online ahead of print.ABSTRACTEosinophilic esophagitis (EoE) is increasingly diagnosed in patients with dysphagia. Type-2 immunity can induce EoE histopathology via non-IgE-dependent mechanisms, possibly involving IgG4 and IL-10. To elucidate the contribution of this response to EoE pathogenesis, we examined its association with clinical and histologic endpoints in adult EoE patients given a two-food elimination diet. IgG4- and IL-10-expressing cells were counted in esophageal biopsies and serum food-specific IgG4 measured at baseline and follow-up. Variabl...
Source: Clinical Immunology - November 28, 2023 Category: Allergy & Immunology Authors: Ramapraba Appanna Domenico Gargano Alessandro Caputo Fabio De Bartolomeis Luca Ricciardi Antonella Santonicola Berenice Stefanelli Laura Caiazza Marialuisa Guarciariello Antonio D'Antonio Raffaella D'Auria Valeria Conti Vincenzo Casolaro Paola Iovino Source Type: research
Challenges for gene editing in common variable immunodeficiency disorders: Current and future prospects
Clin Immunol. 2023 Nov 25:109854. doi: 10.1016/j.clim.2023.109854. Online ahead of print.ABSTRACTThe original CRISPR Cas9 gene editing system and subsequent innovations offers unprecedented opportunities to correct severe genetic defects including those causing Primary Immunodeficiencies (PIDs). Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic PID in adults and children. Unlike many other PIDs, patients meeting CVID criteria do not have a definable genetic defect and cannot be considered to have an inborn error of immunity (IEI). Patients with a CVID phenotype carrying a causative mutatio...
Source: Clinical Immunology - November 28, 2023 Category: Allergy & Immunology Authors: Rohan Ameratunga Euphemia Leung See-Tarn Woon Edward Lea Caroline Allan Lydia Chan Hilary Longhurst Richard Steele Russell Snell Klaus Lehnert Source Type: research
Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis
In this study, we report elevated sEH expression in the joints of CIA (collagen-induced arthritis) rats, concomitant with diminished levels of two significant EpFAs. Additionally, increased sEH expression was detected in both the synovium of CIA rats and in the synovium and fibroblast-like synoviocytes (FLS) of RA patients. The sEH inhibitor TPPU attenuated the migration and invasion capabilities of FLS derived from RA patients and to reduce the secretion of inflammatory factors by these cells. Our findings indicate a pivotal role for sEH in RA pathogenesis and suggest that sEH inhibitors offer a promising new therapeutic ...
Source: Clinical Immunology - November 28, 2023 Category: Allergy & Immunology Authors: Yaoyu Pu Ruijuan Cheng Qiuping Zhang Tianwen Huang Chenyang Lu Zhigang Tang Yutong Zhong Liang Wu Bruce D Hammock Kenji Hashimoto Yubin Luo Yi Liu Source Type: research
Ruxolitinib attenuates acute rejection and can serve as an immune induction therapy in heart transplantation
Clin Immunol. 2023 Nov 24:109851. doi: 10.1016/j.clim.2023.109851. Online ahead of print.ABSTRACTThe benefits of IL2RA antagonists in heart transplant patients are controversial. We aimed to elucidate the effects of IL2RA antagonists and identify targets that could be better than IL2RA antagonists. By using single-cell RNA sequencing of immune cells at different time points in patients receiving IL2RA antagonists, we identified nineteen types of cells. We revealed higher IL2RA expression in regulatory T cells (Tregs), suggesting that IL2RA antagonists attenuated IL-2-induced Treg activation. CD4_C04_IFNGR1 and CD8_C05_IFIT...
Source: Clinical Immunology - November 26, 2023 Category: Allergy & Immunology Authors: Yuan Chang Mengda Xu Yu Zhang Xiao Chen Yixuan Sheng Menghao Tao Hang Zhang Zhenyu Xu Shengshou Hu Jiangping Song Source Type: research
Fibroblasts in immune-mediated inflammatory diseases: The soil of inflammation
Clin Immunol. 2023 Nov 24:109849. doi: 10.1016/j.clim.2023.109849. Online ahead of print.ABSTRACTAs one of the most abundant stromal cells, fibroblasts are primarily responsible for the production and remodeling of the extracellular matrix. Traditionally, fibroblasts have been viewed as quiescent cells. However, recent advances in multi-omics technologies have demonstrated that fibroblasts exhibit remarkable functional diversity at the single-cell level. Additionally, fibroblasts are heterogeneous in their origins, tissue locations, and transitions with stromal cells. The dynamic nature of fibroblasts is further underscore...
Source: Clinical Immunology - November 26, 2023 Category: Allergy & Immunology Authors: Yifan Zhou Tianyu Cao Zhiguo Li Hongjiang Qiao Erle Dang Shuai Shao Gang Wang Source Type: research
Efficacy and safety of 5-aminolevulinic acid in adult-onset Still's disease: A preclinical study in mice and a pilot study in humans
Clin Immunol. 2023 Nov 23;257:109846. doi: 10.1016/j.clim.2023.109846. Online ahead of print.ABSTRACTThe study aimed to investigate the therapeutic effects of 5-aminolevulinic acid/sodium ferrous citrate (5-ALA/SFC) on adult-onset Still's disease (AOSD), specifically focusing on arthritis and macrophage activation syndrome (MAS). We used mouse models to assess the impact of 5-ALA/SFC on collagen-induced arthritis (CIA) and MAS induced by synthetic oligonucleotides containing CpG motifs (CpG-S-ODN). Additionally, we conducted a pilot study with AOSD patients receiving prednisolone (PSL) treatment and 5-ALA/SFC administratio...
Source: Clinical Immunology - November 25, 2023 Category: Allergy & Immunology Authors: Tomohiro Koga Remi Sumiyoshi Yoshika Tsuji Ken Kodama Yushiro Endo Kaori Furukawa Atsushi Kawakami Source Type: research
B-cell activating factor gene variants in multiple sclerosis: Possible associations with disease susceptibility among females
Clin Immunol. 2023 Nov 21:109847. doi: 10.1016/j.clim.2023.109847. Online ahead of print.ABSTRACTAlthough B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility. 156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-P...
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Charalampos Skarlis Vassilis Papadopoulos Sylvia Raftopoulou Clio P Mavragani Maria-Eleftheria Evangelopoulos Source Type: research
Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk
CONCLUSION: While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, β2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.PMID:37995947 | DOI:10.1016/j.clim.2023.109845 (Source: Clinical Immunology)
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Marc Emmenegger Vishalini Emmenegger Srikanth Mairpady Shambat Thomas C Scheier Alejandro Gomez-Mejia Chun-Chi Chang Pedro D Wendel-Garcia Philip K Buehler Thomas Buettner Dirk Roggenbuck Silvio D Brugger Katrin B M Frauenknecht Source Type: research
B-cell activating factor gene variants in multiple sclerosis: Possible associations with disease susceptibility among females
Clin Immunol. 2023 Nov 21:109847. doi: 10.1016/j.clim.2023.109847. Online ahead of print.ABSTRACTAlthough B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility. 156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-P...
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Charalampos Skarlis Vassilis Papadopoulos Sylvia Raftopoulou Clio P Mavragani Maria-Eleftheria Evangelopoulos Source Type: research
Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk
CONCLUSION: While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, β2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.PMID:37995947 | DOI:10.1016/j.clim.2023.109845 (Source: Clinical Immunology)
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Marc Emmenegger Vishalini Emmenegger Srikanth Mairpady Shambat Thomas C Scheier Alejandro Gomez-Mejia Chun-Chi Chang Pedro D Wendel-Garcia Philip K Buehler Thomas Buettner Dirk Roggenbuck Silvio D Brugger Katrin B M Frauenknecht Source Type: research
B-cell activating factor gene variants in multiple sclerosis: Possible associations with disease susceptibility among females
Clin Immunol. 2023 Nov 21:109847. doi: 10.1016/j.clim.2023.109847. Online ahead of print.ABSTRACTAlthough B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility. 156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-P...
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Charalampos Skarlis Vassilis Papadopoulos Sylvia Raftopoulou Clio P Mavragani Maria-Eleftheria Evangelopoulos Source Type: research
Antiphospholipid antibodies are enriched post-acute COVID-19 but do not modulate the thrombotic risk
CONCLUSION: While we have recapitulated previous findings, we conclude that the presence of the aPL, most notably PT, β2GPI, AnV IgM, and CL IgG in COVID-19 are not associated with a higher incidence of thrombotic events.PMID:37995947 | DOI:10.1016/j.clim.2023.109845 (Source: Clinical Immunology)
Source: Clinical Immunology - November 23, 2023 Category: Allergy & Immunology Authors: Marc Emmenegger Vishalini Emmenegger Srikanth Mairpady Shambat Thomas C Scheier Alejandro Gomez-Mejia Chun-Chi Chang Pedro D Wendel-Garcia Philip K Buehler Thomas Buettner Dirk Roggenbuck Silvio D Brugger Katrin B M Frauenknecht Source Type: research
A novel homozygous Y140X mutation of ISG15 causes diverse type I interferonopathies in sibling patients with cutaneous lesions or recurrent parenchymal pneumonia
CONCLUSIONS: We report two sibling patients harboring the same novel ISG15 mutation showing diverse clinical features, and one harbored a rare phenotype of pneumonia. These findings expand the clinical spectrum of ISG15 deficiency and identify baricitinib as therapeutic candidate.PMID:37984483 | DOI:10.1016/j.clim.2023.109844 (Source: Clinical Immunology)
Source: Clinical Immunology - November 20, 2023 Category: Allergy & Immunology Authors: Qiling Xu Wenyan Li Qian Zhao Lu Zhao Ge Lv Gan Sun Yelei Gao Yuan Ding Zhiyong Zhang Lina Zhou Yongwen Chen Xuemei Tang Jin Zhu Xiaodong Zhao Yunfei An Source Type: research
