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Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.

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Title: Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.
Authors: Saleh, Qais W., Mohammadnejad, Afsaneh, Tepel, Martin
Source: Frontiers in Immunology; 2023, p1-12, 12p
Subject Terms: KIDNEY transplantation, REGULATORY T cells, MONONUCLEAR leukocytes, INFLAMMATION, REGULATOR genes
Abstract: Background: Immunosuppressive treatment of kidney transplant recipients is mainly aimed at pro-inflammatory T effector cells, yet they also target the immunosuppressive T regulatory cells. Here, we test the hypothesis that low levels of the master gene regulator of T regulatory cells, forkhead box P3 (FOXP3) splice variants, are associated with prolonged inflammatory responses to stimuli. Methods: From blood samples obtained the first - and 29th day post-transplant, we extracted peripheral blood mononuclear cells and measured mRNA levels of Total FOXP3, pre-mature RNA FOXP3 (pre-mRNA FOXP3), full length FOXP3 (FOXP3fl) and, FOXP3 splice variant excluding exon two (FOXP3d2). We defined the primary outcome as the number of days in which C reactive protein (CRP) was above 50 mg/L. CRP levels were gathered in two periods, the first from the second to 29 days post-transplant, and the second from 30 to 57 days posttransplant. The association was tested using adjusted negative binomial regression. Results: From 507 included kidney transplant recipients, 382 recipients had at least one CRP measurement >50 mg/L in the first period, median duration of elevated CRP was 4 days [interquartile range (IQR) 2 to 6]. In the second period, 69 recipients had at least one CRP measurement >50 mg/L, median duration of elevated CRP was 3 days [IQR 2 to 5]. In the first period, we found a significant association between lower levels of Total FOXP3 and prolonged duration of CRP elevation, incidence rate ratio 0.61 (95% confidence interval 0.46-0.80), p<0.01. Conclusion: Lower levels of total FOXP3 mRNA levels in peripheral blood of kidney transplant recipients are associated with prolonged duration of inflammatory responses regardless of the underlying stimuli. [ABSTRACT FROM AUTHOR]
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Complementary Index
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  Data: Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.
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  Data: Frontiers in Immunology; 2023, p1-12, 12p
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22KIDNEY+transplantation%22&quot;&gt;KIDNEY transplantation&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22REGULATORY+T+cells%22&quot;&gt;REGULATORY T cells&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22MONONUCLEAR+leukocytes%22&quot;&gt;MONONUCLEAR leukocytes&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22INFLAMMATION%22&quot;&gt;INFLAMMATION&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22REGULATOR+genes%22&quot;&gt;REGULATOR genes&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Immunosuppressive treatment of kidney transplant recipients is mainly aimed at pro-inflammatory T effector cells, yet they also target the immunosuppressive T regulatory cells. Here, we test the hypothesis that low levels of the master gene regulator of T regulatory cells, forkhead box P3 (FOXP3) splice variants, are associated with prolonged inflammatory responses to stimuli. Methods: From blood samples obtained the first - and 29&lt;superscript&gt;th&lt;/superscript&gt; day post-transplant, we extracted peripheral blood mononuclear cells and measured mRNA levels of Total FOXP3, pre-mature RNA FOXP3 (pre-mRNA FOXP3), full length FOXP3 (FOXP3fl) and, FOXP3 splice variant excluding exon two (FOXP3d2). We defined the primary outcome as the number of days in which C reactive protein (CRP) was above 50 mg/L. CRP levels were gathered in two periods, the first from the second to 29 days post-transplant, and the second from 30 to 57 days posttransplant. The association was tested using adjusted negative binomial regression. Results: From 507 included kidney transplant recipients, 382 recipients had at least one CRP measurement &gt;50 mg/L in the first period, median duration of elevated CRP was 4 days [interquartile range (IQR) 2 to 6]. In the second period, 69 recipients had at least one CRP measurement &gt;50 mg/L, median duration of elevated CRP was 3 days [IQR 2 to 5]. In the first period, we found a significant association between lower levels of Total FOXP3 and prolonged duration of CRP elevation, incidence rate ratio 0.61 (95% confidence interval 0.46-0.80), p&lt;0.01. Conclusion: Lower levels of total FOXP3 mRNA levels in peripheral blood of kidney transplant recipients are associated with prolonged duration of inflammatory responses regardless of the underlying stimuli. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: &lt;i&gt;Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder&#39;s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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    Identifiers:
      – Type: doi
        Value: 10.3389/fimmu.2023.1252857
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      – Code: eng
        Text: English
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      Pagination:
        PageCount: 12
        StartPage: 1
    Subjects:
      – SubjectFull: KIDNEY transplantation
        Type: general
      – SubjectFull: REGULATORY T cells
        Type: general
      – SubjectFull: MONONUCLEAR leukocytes
        Type: general
      – SubjectFull: INFLAMMATION
        Type: general
      – SubjectFull: REGULATOR genes
        Type: general
    Titles:
      – TitleFull: Lower levels of FOXP3 are associated with prolonged inflammatory responses in kidney transplant recipients.
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            NameFull: Saleh, Qais W.
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            NameFull: Mohammadnejad, Afsaneh
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            NameFull: Tepel, Martin
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          Dates:
            – D: 27
              M: 09
              Text: 2023
              Type: published
              Y: 2023
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            – TitleFull: Frontiers in Immunology
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