Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • In our cohort bronchiectasis was

    2018-11-03

    In our cohort bronchiectasis was not associated with a higher mortality or a longer diagnostic delay. Bronchiectasis has been associated with a diagnostic delay in other studies (Brent et al., 2016) and is considered to be an important predictor of the prognosis of the disease. However an association with mortality has not always been found. We did not find an association with mortality or diagnostic delay possibly because we did not differentiate between mild and severe bronchiectasis. In our study 36% (27 of 75 patients) of the patients had bronchiectasis. The reported prevalence in other cohorts, consisting largely of CVID patients, varied from 11.2 to 47% (Quinti et al., 2011; Resnick et al., 2012; Brent et al., 2016). Limitations of our study are mainly related to the retrospective character. Because of this not all data were complete. Infection frequency before ART was determined anamnestically, while during ART all infections were physician-confirmed. The latter is a stricter interpretation. The decrease of infection frequency during ART is very significant but should be interpreted with caution. In observational studies without control groups the phenomenon of regression to the mean can be inadvertently classified as a therapeutic effect. We find this unlikely in our study because the decision to start ART was based on an increase of infection frequency and spontaneous decrease of infection frequency in immunodeficient patients is not often seen. Another limitation is that the diagnoses of the patients receiving IVIG were different from the patients receiving SCIG. Patients receiving IVIG had more severe forms of immunodeficiency. However, in our study we did not intend to directly compare IVIG with SCIG, but rather to investigate the efficacy of ART as a whole. During the long follow up Go 6976 there have inevitably been changes in diagnostic protocols and definition of antibody response. The IgG pneumococcal antibody response was categorized using the diagnostic criteria of 2005 (Bonilla et al., 2005), because these formed the basis for the decision to start ART in most patients. In 2015 the criteria were updated (Bonilla et al., 2015). The new criteria have a stricter definition of an adequate antibody response.
    Funding Sources
    Conflicts of Interest
    Author Contributions
    Acknowledgements
    Introduction Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial hyperplasia, causing cartilage and bone destruction (Firestein, 1996). The synovial tissues of RA patients contain diverse innate and adaptive immune cells activated by self or non-self antigens (Firestein, 2003). In particular, synovial macrophages are activated by the stimulation of a variety of inflammatory mediators secreted from surrounding inflammatory cells or via cell-to-cell contact. Activated macrophages, in turn, release matrix metalloproteinases and pro-inflammatory cytokines and chemokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), granulocyte/macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein (MCP-1), thereby contributing to chronic inflammation (Firestein, 2003; Kinne et al., 2000). Moreover, the number of synovial macrophages, but not the number of lymphocytes, correlates with the progression of RA (Mulherin et al., 1996). In sum, previous studies suggest that macrophages are the major cell type responsible for RA pathology. Nuclear factor of activated T cells 5 (NFAT5), also known as tonicity-responsive enhancer-binding protein (TonEBP), is a transcription factor whose DNA binding domain shares structural homology with NF-κB and other members of the NFAT family (Lopez-Rodriguez et al., 1999). In response to osmotic stress, NFAT5 is activated via p38 mitogen-activated protein kinase (MAPK) signaling to protect cells from hypertonic stimulation (Ko et al., 2002). Therefore, NFAT5 has important roles in different tissues normally exposed to hypertonicity, such as kidney, skin, and eye (Miyakawa et al., 1999; Go et al., 2004; Neuhofer, 2010; Sawazaki et al., 2014). It has also been implicated in several physiologic and pathologic conditions, including cancer cell proliferation and invasion (Kuper et al., 2014; Jauliac et al., 2002). Recently, evidence has emerged that NFAT5 is activated by isotonic stimuli. For example, NFAT5 induces the expression of toll-like receptor (TLR)-mediated inflammatory genes in macrophages in a tonicity-independent manner (Buxadé et al., 2012; Kim et al., 2013). High salt and TLR ligation activate distinct sets of downstream target genes in a NFAT5-dependent manner (Kim et al., 2014). While ROS are essential for this, their source differs depending on the context: mitochondria for high salt and xanthine oxidase for TLR (Kim et al., 2014). Moreover, the two pathways are mutually suppressive (Kim et al., 2013). Therefore, to apply anti-NFAT5 therapies to chronic inflammatory diseases, it may be necessary to selectively inhibit its inflammatory effects without affecting its osmotic effects since the latter are involved in cellular homeostasis and cytoprotection (Miyakawa et al., 1999).