Increased plasma levels of pentraxin 3 in patients with multiple sclerosis and neuromyelitis optica

2012 ◽  
Vol 19 (7) ◽  
pp. 926-931 ◽  
Author(s):  
Honghao Wang ◽  
Kai Wang ◽  
Conghui Wang ◽  
Xiaonan Zhong ◽  
Wei Qiu ◽  
...  

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are immune-mediated inflammatory diseases of the central nervous system. In the acute phase of these diseases, secondary ischemia due to inflammation-induced endothelial dysfunction may be an important pathological change. Pentraxin 3 (PTX3) is a pro-inflammatory protein and a novel biomarker of inflammatory vascular diseases. Objective: We aimed to determine whether PTX3 levels are elevated in MS and NMO patients. Methods: The concentrations of plasma PTX3 were measured using an enzyme-linked immunosorbent assay in 22 MS patients, 26 NMO patients, 15 acute cerebral infarction (CI) patients, 11 mild headache patients, and 14 volunteer controls. Results: During relapse, plasma PTX3 levels were higher in MS patients than in headache patients ( p=0.003) and controls ( p<0.001). Plasma PTX3 levels were also increased in NMO patients compared with CI patients ( p=0.011), headache patients ( p<0.001) and controls ( p<0.001). CI patients showed elevated PTX3 levels compared with controls ( p=0.008). MS and NMO patients showed a trend toward an increased disease disability with higher plasma PTX3 during relapse (MS: p=0.005; NMO: p<0.001). Plasma PTX3 levels were remarkably lower in remission than in the relapse stage (MS: p<0.001; NMO: p<0.001). Conclusion: Plasma PTX3 level is associated with inflammatory responses in MS and NMO.

2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Leila Khani ◽  
Mir Hadi Jazayeri ◽  
Reza Nedaeinia ◽  
Mahmood Bozorgmehr ◽  
Seyed Masood Nabavi ◽  
...  

Abstract Background Multiple sclerosis (MS) and neuromyelitis optica syndrome disease (NMOSD) are inflammatory diseases of the central nervous system. The pathogenesis and treatments for these two conditions are very different. Natural killer (NK) and natural killer T (NKT) cells are immune cells with an important role in shaping the immune response. B cells are involved in antigen presentation as well as antibody and cytokine production. There is conflicting evidence of the roles of NK, NKT, and B cells in the two conditions. We aimed to compare the frequency of CD3−CD16+CD56+NK, CD3+ CD56+ NKT, and CD5+CD19+ B cells in the peripheral blood and serum Interleukin-10 (IL-10) in patients with MS and NMOSD. Methods CD19+CD5+ B, CD3− CD16+CD56+ NK, and CD3+CD56+ NKT cells were quantitated by flow cytometry in 15 individuals with Interferon-Beta (IFN-β) treated relapsing–remitting MS (RRMS), 15 untreated RRMS, and 15 NMOSD patients as well as 30 healthy controls (HC). Serum IL-10 was measured using an enzyme-linked immunosorbent assay (ELISA). Results The percentage of CD3−CD56+CD16+ NK cells in the peripheral blood of IFN-treated MS (1.81 ± 0.87) was significantly lower than for untreated RRMS (4.74 ± 1.80), NMOSD (4.64 ± 1.26) and HC (5.83 ± 2.19) (p < 0.0001). There were also differences for the percentage of CD3−CD16+ and CD3−CD56+ cells (p < 0.001 and p < 0.0007; respectively). IFN-treated RRMS (2.89 ± 1.51) had the lowest proportion of CD3+CD56+ among the study groups (p < 0.002). Untreated RRMS (5.56 ± 3.04) and NMOSD (5.47 ± 1.24) had higher levels of CD3+CD56+ than the HC (3.16 ± 1.98). The mean percentage of CD19+CD5+ B cells in the peripheral blood of untreated RRMS patients (1.32 ± 0.67) was higher compared to the patients with NMOSD (0.30 ± 0.20), HC (0.5 ± 0.22) and IFN-treated RRMS (0.81 ± 0.17) (p < 0.0001). Serum interleukin-10 was significantly higher in the IFN-treated RRMS (8.06 ± 5.39) and in HC (8.38 ± 2.84) compared to untreated RRMS (5.07 ± 1.44) and the patients with NMOSD (5.33 ± 2.56) (p < 0.003). Conclusions The lower proportion of CD3−CD56+ CD16+ NK and CD3+CD56+ cells in peripheral blood of IFN-treated RRMS compared to other groups suggests the importance of immunomodulation in patients with RRMS disorder. Based on the differences in CD19+CD5+ B cells and serum IL-10 between patients and HC, supplementary assessments could be of value in clarifying their roles in autoimmunity.


2021 ◽  
Vol 12 (2) ◽  
pp. 199-204
Author(s):  
Milad Moayednia ◽  
◽  
Leila Dehghani ◽  
Amir Safi ◽  
Vahid Shaygannejad ◽  
...  

Introduction: Midkine (MK), a heparin-binding growth factor, is involved in neurological diseases by mediating the inflammatory responses through enhancing the leukocyte migration. The present study assesses the serum concentration of this growth factor among newly developed Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) patients. Methods: The present research, as a cross-sectional study, was performed at Isfahan University of Medical Sciences, Isfahan City, Iran. All samples were selected from patients who visited Kashani and Alzahra hospitals for two years (2014 to 2016). The MK level was assessed in 80 new MS cases, 80 NMO patients, and 80 healthy subjects. After collecting blood sera samples, MK serum level was measured using the ELISA. The obtained data were analyzed in SPSS. Results: The Mean±SD MK level was 1038.58±44.73 pg/mL in the MS group, which was significantly higher than the Mean±SD MK level in the NMO (872.62±55.42 pg/mL) and control groups (605.02±9.42 pg/mL). Conclusion: Overall, these results demonstrated that MK plays a prominent role in inflammatory reactions and neuroautoimmune diseases, especially in MS. So, the MK level may be used for earlier diagnosis and also prevention of disease progression by using a special inhibitor.


2020 ◽  
Vol 11 ◽  
Author(s):  
Hyunjin Kim ◽  
Youngin Lee ◽  
Yong-Hwan Kim ◽  
Young-Min Lim ◽  
Ji Sung Lee ◽  
...  

Background: Differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) is crucial in the field of diagnostics because, despite their similarities, the treatments for these two diseases are substantially different, and disease-modifying treatments for MS can worsen NMOSD. As brain magnetic resonance imaging (MRI) is an important tool to distinguish the two diseases, extensive research has been conducted to identify the defining characteristics of MRI images corresponding to these two diseases. However, the application of such research in clinical practice is still limited. In this study, we investigate the applicability of a deep learning-based algorithm for differentiating NMOSD from MS.Methods: In this study, we included 338 participants (213 patients with MS, 125 patients with NMOSD) who visited the Asan medical center between February 2009 and February 2020. A 3D convolutional neural network, which is a deep learning-based algorithm, was trained using fluid-attenuated inversion recovery images and clinical information of the participants. The performance of the final model in differentiating NMOSD from MS was evaluated and compared with that of two neurologists.Results: The deep learning-based model exhibited an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.75–0.89). It differentiated NMOSD from MS with an accuracy of 71.1% (sensitivity = 87.8%, specificity = 61.6%), which is comparable to that exhibited by the neurologists. The intra-rater reliability of the two neurologists was moderate (κ = 0.47, 0.50), which was in contrast with the consistent classification of the deep learning-based model.Conclusion: The proposed model was verified to be capable of differentiating NMOSD from MS with accuracy comparable to that of neurologists, exhibiting the advantage of consistent classification. As a result, it can aid differential diagnosis between two important central nervous system inflammatory diseases in clinical practice.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 396
Author(s):  
Malihe Eskandarpour ◽  
Miles A. Nunn ◽  
Wynne Weston-Davies ◽  
Virginia L. Calder

Retinal vascular diseases have distinct, complex and multifactorial pathogeneses yet share several key pathophysiological aspects including inflammation, vascular permeability and neovascularisation. In non-infectious posterior uveitis (NIU), retinal vasculitis involves vessel leakage leading to retinal enlargement, exudation, and macular oedema. Neovascularisation is not a common feature in NIU, however, detection of the major angiogenic factor—vascular endothelial growth factor A (VEGF-A)—in intraocular fluids in animal models of uveitis may be an indication for a role for this cytokine in a highly inflammatory condition. Suppression of VEGF-A by directly targeting the leukotriene B4 (LTB4) receptor (BLT1) pathway indicates a connection between leukotrienes (LTs), which have prominent roles in initiating and propagating inflammatory responses, and VEGF-A in retinal inflammatory diseases. Further research is needed to understand how LTs interact with intraocular cytokines in retinal inflammatory diseases to guide the development of novel therapeutic approaches targeting both inflammatory mediator pathways.


Author(s):  
Jiexue Pan ◽  
Chengliang Zhou ◽  
Zhiyang Zhou ◽  
Zuwei Yang ◽  
Tiantian Dai ◽  
...  

Abstract Purpose Pentraxin 3 (PTX3) plays a crucial role in cumulus expansion and fertilization. The ovarian PTX3 level in polycystic ovary syndrome (PCOS) remains uncertain. In the present study, we investigated the follicular PTX3 levels and found the influence of reproductive hormones on ovarian PTX3 concentration. Methods This study was based on 204 healthy-weight women (102 PCOS and 102 normal ovulating subjects) undergoing in vitro fertilization (IVF). Follicular fluid (FF) was collected during oocyte retrieval. The PTX3 levels and other hormone levels in FF samples were analyzed by enzyme-linked immunosorbent assay (ELISA). Results The PTX3 level in the follicle was significantly higher in the healthy-weight PCOS women than controls. Positive correlations were found between ovarian PTX3 level and the existence of PCOS, cycle length, basal LH to FSH ratio and TT in serum, antral follicle count, and ovarian insulin and androgen level, and inverse correlations with the basal serum PRL and ovarian SHBG. In multivariant linear regression analysis, the presence of PCOS diagnosis, participants’ basal LH to FSH ratio, and ovarian androstenedione level were the main predictors of ovarian PTX3 level among the enrolled subjects. Conclusion Elevated ovarian PTX3 level supports the low-grade chronic inflammatory state in the follicles of PCOS. The existence of PCOS, disturbed pituitary gland, and ovarian hyperandrogenism might also be related to this state of low-grade chronic inflammation and could be a subject of further study.


2021 ◽  
Vol 22 (16) ◽  
pp. 8946
Author(s):  
Karina Maciak ◽  
Sylwia Pietrasik ◽  
Angela Dziedzic ◽  
Justyna Redlicka ◽  
Joanna Saluk-Bijak ◽  
...  

Multiple sclerosis (MS) and Devic’s disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoyan Yang ◽  
Jing Peng ◽  
Xiaoxi Huang ◽  
Peidong Liu ◽  
Juan Li ◽  
...  

BackgroundNeuromyelitis optica spectrum disorders (NMOSDs) are severe inflammatory diseases mediated mainly by humoral and cellular immunity. Circulating follicular helper T (Tfh) cells are thought to be involved in the pathogenesis of NMOSD, and serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of Tfh cells on B-cell-mediated humoral immunity. Immune cell and cytokine changes during the dynamic relapsing and remitting processes in NMOSD require further exploration.Patients and methodsBlood samples were collected from 36 patients in acute and recovery phases of NMOSD, 20 patients with other noninflammatory neurological diseases (ONND) and 20 age- and sex-matched healthy volunteers. CD4+CXCR5+PD-1+ Tfh cells were detected by flow cytometry, and serum CXCL13 levels were assessed by enzyme-linked immunosorbent assay (ELISA).ResultsThe percentage of CD4+CXCR5+PD-1+ Tfh cells was significantly higher during the acute phase than during the recovery phase, and serum CXCL13 levels were significantly higher in patients in the acute and recovery phases of NMOSD than in the ONND and control groups. The Tfh cell percentage was positively correlated with CXCL13 levels, and both were positively correlated with Expanded Disability Status Scale (EDSS) scores and cerebrospinal fluid protein levels in patients with acute NMOSD.ConclusionCirculating Tfh cells level has the potential to be a biomarker of disease severity.


Author(s):  
Aimin Wu ◽  
Xiaonan Zhong ◽  
Honghao Wang ◽  
Wen Xu ◽  
Chen Cheng ◽  
...  

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. IL-21/IL-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum IL-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) IL-21 in MS and NMO patients still remain unknown.Object:To detect the CSF concentration of IL-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity.Methods:CSF IL-21 was detected by an enzyme-linked immunosorbent assay (ELISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16).Results:CSF concentration of the IL-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between IL-21 and complement in NMO cohort (p=0.023) and high IL-21 levels in autoantibody-positive subgroup (p=0.027).Conclusions:The concentration of CSF IL-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO.


2012 ◽  
Vol 19 (3) ◽  
pp. 289-298 ◽  
Author(s):  
Chao Quan ◽  
Hai Yu ◽  
Jian Qiao ◽  
Baoguo Xiao ◽  
Guixian Zhao ◽  
...  

Background: The effective treatment of neuromyelitis optica (NMO) with rituximab has suggested an important role for B cells in NMO pathogenesis. Objective: To explore the antibody-independent function of B cells in NMO and relapsing–remitting multiple sclerosis (RRMS). Methods: Fifty-one NMO patients and 42 RRMS patients in an acute relapse phase and 37 healthy controls (HC) were enrolled in the study. The B cell expression of B cell activating factor receptor (BAFF-R), CXCR5 and very late antigen-4 (VLA-4), the B cell production of interleukin (IL)-10 and interferon (IFN)-γ and the proportion of circulating memory and CD19+CD24highCD38high regulatory B cells were evaluated by flow cytometry. The cerebrospinal fluid (CSF) levels of BAFF and CXCL13 were determined by enzyme-linked immunosorbent assay (ELISA). Results: The CD19+CD24highCD38high regulatory B cell levels and the B cell expression of IL-10 were significantly lower in NMO patients than in RRMS patients and the HC. In aquaporin-4 antibody (AQP4-ab)-positive NMO patients, the B cell IL-10 production and CD19+CD24highCD38high regulatory B cell levels were even lower than in AQP4-ab-negative NMO patients. The CSF BAFF and CXCL13 levels were significantly higher in NMO patients than in patients with RRMS and other non-inflammatory neurologic diseases (ONDs). Conclusions: The immuno-regulatory properties of B cells are significantly impaired in NMO patients and particularly in AQP4-ab-positive NMO patients. The elevated CSF levels of BAFF and CXCL13 in NMO suggest an enhanced intrathecal B cell recruitment and activation. Our results further define the distinct immunological nature of NMO and RRMS from the B cell perspective.


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