scholarly journals Abnormal Exacerbation of Moderately Differentiated Gastric Adenocarcinoma in a Patient with TAFRO Syndrome: An Impaired Tumor Immunity?

2022 ◽  
pp. 7-11
Author(s):  
Tadaaki Inano ◽  
Hajime Yasuda ◽  
Yutaka Tsukune ◽  
Miyuki Tsutsui ◽  
Nadila Wali ◽  
...  

TAFRO syndrome is a relatively new disease entity first reported in 2010. We report a case of TAFRO syndrome accommodated by abnormal exacerbation of moderately differentiated gastric adenocarcinoma. The pathophysiology of TAFRO syndrome is largely unknown, but because the disease often responds to immunosuppressive therapy and also because T follicular helper (Tfh) cells are reported to be drastically decreased in TAFRO syndrome, involvement of a dysregulated immune system can be speculated. Growing evidence points toward a pivotal role of Tfh cells in tumor immunity through supporting ectopic lymphoid structures, which are recruitment sites for cells directly engaging in antitumor activity such as CD8<sup>+</sup> T cells, NK cells, and macrophages. In fact, Tfh cells are reported to positively correlate with longer survival in human colorectal and breast cancer. Combined with our observations of hyperprogressive gastric cancer in the presented patient, an impaired tumor immunity is strongly indicated in TAFRO syndrome.

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Xueli Fan ◽  
Yanfang Jiang ◽  
Jinming Han ◽  
Jingyao Liu ◽  
Yafen Wei ◽  
...  

Objective. This study aimed to examine the potential role of memory T follicular helper (Tfh) cells in patients with neuromyelitis optica/neuromyelitis optica spectrum disorders (NMO/NMOSD).Methods. The percentages of different subsets of circulating memory Tfh cells in 25 NMO/NMOSD patients before and after treatment as well as in 17 healthy controls were examined by flow cytometry. The levels of IL-21 and AQP4 Ab in plasma and CSF were measured by ELISA.Results. The percentages and numbers of circulating memory Tfh cells, ICOS+, CCR7−, CCR7−ICOS+, CCR7+, CCR7+ICOS+memory Tfh cells, and the levels of IL-21 in plasma and CSF were significantly increased in NMO/NMOSD patients. The percentages of CCR7−and CCR7−ICOS+memory Tfh cells were positively correlated with ARR, plasma IL-21, and AQP4 Ab levels. The percentages of CCR7+and CCR7+ICOS+memory Tfh cells were positively correlated with CSF white blood cell counts, proteins, and IL-21 levels. Treatment with corticosteroids significantly reduced the numbers of CCR7−ICOS+and CCR7+ICOS+memory Tfh cells as well as plasma IL-21 levels in patients with partial remission.Conclusions. Our findings indicate that circulating memory Tfh cells may participate in the relapse and development of NMO/NMOSD and may serve as a new therapeutic target.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jianping Wu ◽  
David Cui ◽  
Xianzhi Yang ◽  
Jianzhou Lou ◽  
Jie Lin ◽  
...  

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. The role of T follicular helper (TFH) cells in EV71-infected children remains unclear in regulating humoral immunity. The frequency of circulating ICOShigh/PD-1highCXCR5+CD4+TFH cells in the children with mild and severe EV71 infection and healthy controls (HC) was detected by flow cytometry, respectively. IL-21 and IL-6 mRNA expression and their serum levels, Bcl-6 mRNA expression, and specific neutralizing antibodies against EV71 (NAb-EV71) were measured. In the acute stage of patients with EV71 infection, increased frequencies of circulating TFH cells with ICOShighand PD-1highexpression in the mild and severe patients were observed, and the positive correlations among the frequencies of circulating TFH cells and the serum levels of IL-21, IL-6, and NAb-EV71 titres were detected, respectively. Moreover, the expressions of IL-6 and IL-21 mRNA in PBMCs from patients were also significantly higher than those of HC. However, further analysis did not reveal any significant differences between mild and severe patients. These data indicate a role of TFH cells and associated cytokines in modulating the humoral response during the pathogenesis of EV71 infection.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Ding ◽  
Rui Su ◽  
Ruihe Wu ◽  
Hongwei Xue ◽  
Yanyan Wang ◽  
...  

Balance of Tfh/Tfr cell is critically important for the maintenance of immune tolerance, as evidenced by the fact that T follicular helper (Tfh) cells are central to the autoantibodies generation through providing necessary help for germinal center (GC) B cells, whereas T follicular regulatory (Tfr) cells significantly inhibit autoimmune inflammation process through restraining Tfh cell responses. However, signals underlying the regulation of Tfh and Tfr cells are largely undefined. Regulatory B cells (Bregs) is a heterogeneous subpopulation of B cells with immunosuppressive function. Considerable advances have been made in their functions to produce anti‐inflammatory cytokines and to regulate Th17, Th1, and Treg cells in autoimmune diseases. The recent identification of their correlations with dysregulated Tfr/Tfh cells and autoantibody production makes Bregs an important checkpoint in GC response. Bregs exert profound impacts on the differentiation, function, and distribution of Tfh and Tfr cells in the immune microenvironment. Thus, unraveling mechanistic information on Tfh-Breg and Tfr-Breg interactions will inspire novel implications for the establishment of homeostasis and prevention of autoantibodies in diverse diseases. This review summarizes the dysregulation of Tfh/Tfr cells in autoimmune diseases with a focus on the emerging role of Bregs in regulating the balance between Tfh and Tfr cells. The previously unsuspected crosstalk between Bregs and Tfh/Tfr cells will be beneficial to understand the cellular mechanisms of autoantibody production and evoke a revolution in immunotherapy for autoimmune diseases.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 13.2-14
Author(s):  
H. Forsblad-D’elia ◽  
U. Hellman ◽  
A. Kumar ◽  
K. Lejon

Background:The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed.Objectives:The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors.Methods:Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI.Results:When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (Rs=-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (Rs =–0,476 p=0,053 and Rs =–0,522 p=0,032 respectively).Conclusion:TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS.Disclosure of Interests:None declared


2020 ◽  
Vol 61 ◽  
pp. 101071 ◽  
Author(s):  
Gilda Varricchi ◽  
Leonardo Bencivenga ◽  
Remo Poto ◽  
Antonio Pecoraro ◽  
Mohamed H. Shamji ◽  
...  
Keyword(s):  

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Lulu Sun ◽  
Ruixue Kong ◽  
Hua Li ◽  
Dashan Wang

T follicular helper (Tfh) cells represent a novel subset of CD4+ T cells which can provide critical help for germinal center (GC) formation and antibody production. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), inducible costimulatory molecule (ICOS), B cell lymphoma 6 (BCL-6), and the secretion of interleukin-21 (IL-21). Given the important role of Tfh cells in B cell activation and high-affinity antibody production, Tfh cells are involved in the pathogenesis of many human diseases. Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases characterized by symptoms such as diarrhea, abdominal pain, and weight loss. Ulcerative colitis (UC) and Crohn’s disease (CD) are the most studied types of IBD. Dysregulated mucosal immune response plays an important role in the pathogenesis of IBD. In recent years, many studies have identified the critical role of Tfh cells and IL-21 in the pathogenic process IBD. In this paper, we will discuss the role of Tfh cells and IL-21 in IBD pathogenesis.


CytoJournal ◽  
2005 ◽  
Vol 2 ◽  
pp. 5 ◽  
Author(s):  
Gladwyn Leiman

This issue of CytoJournal contains an article on screening for anal intraepithelial neoplasia in high-risk male patients. This accompanying Editorial focuses on current understanding of this relatively new disease entity, with insights as to the potential role of screening cytopathology in the epidemiology, pathophysiology and clinical management of this HIV and HPV related anal lesion, which predominates in male patients living long-term with AIDS. Mention is made of techniques of obtaining samples, methods of preparation, and morphologic classification. Issues of anoscopic confirmation, as well as topical and surgical management are emphasized. The similarity of initial experiences in anal screening to problems encountered early in cervical cancer screening programs several decades ago, are highlighted.


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