Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy

Caneparo, Valeria; Pastorelli, Luca; Pisani, Laura Francesca; Bruni, Barbara; Prodam, Flavia; Boldorini, Renzo; Roggenbuck, Dirk; Vecchi, Maurizio; Landolfo, Santo; Gariglio, Marisa; Andrea, Marco De

doi:10.1097/mib.0000000000000926

Cited by 27 publications

(26 citation statements)

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“…The transcriptional data correlated well with immunoblotting studies exhibiting increased protein expression of AIM2 and IFI16 in the colonic mucosa of active patients (Vanhove et al, 2015). These findings were independently verified by a study which confirmed elevated expression by immunohistochemistry of IFI16 in intestinal samples from both ulcerative colitis and Crohn's disease patients (Caneparo et al, 2016). Moreover, the latter study revealed elevated IFI16 expression limited to the intestinal epithelial cells of IBD patients.…”

Section: Ifi16 Assembles An Inflammasome In the Nucleussupporting

confidence: 76%

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Common Differences: The Ability of Inflammasomes to Distinguish Between Self and Pathogen Nucleic Acids During Infection

Lupfer

Rippee-Brooks

Anand

2019

International Review of Cell and Molecular Biology

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The innate immune system detects the presence of pathogens based on detection of non-self. In other words, most pathogens possess intrinsic differences that can distinguish them from host cells. For example, bacteria and fungi have cell walls comprised of peptidoglycan and carbohydrates (like mannans), respectively. Germline encoded pattern recognition receptors (PRRs) of the Toll-like receptor (TLR) and Ctype lectin receptor (CLR) family have the ability to detect such unique pathogen associated features. However, some TLRs and members of the RIG-I-like receptor (RLR), NOD-like receptor (NLR) or AIM2-like receptor (ALR) family can sense pathogen invasion based on pathogen nucleic acids. Nucleic acids are not unique to pathogens, thus raising the question of how such PRRs evolved to detect pathogens but not self. In this chapter, we will examine the PRRs that sense pathogen nucleic acids and subsequently activate the inflammasome signaling pathway. We will examine the selective mechanisms by which these receptors distinguish pathogens from 'self', and discuss the importance of such pathways in disease development in animal models and human patients.

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Section: Ifi16 Assembles An Inflammasome In the Nucleussupporting

confidence: 76%

“…Although data was not included, IFI16 staining was conspicuously absent in intestinal epithelial cells from other non-IBD inflammatory conditions (Caneparo et al, 2016).…”

Section: Ifi16 Assembles An Inflammasome In the Nucleusmentioning

confidence: 99%

Common Differences: The Ability of Inflammasomes to Distinguish Between Self and Pathogen Nucleic Acids During Infection

Lupfer

Rippee-Brooks

Anand

2019

International Review of Cell and Molecular Biology

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“…In the same setting, the dermal inflammatory infiltrate has been found positive for IFI16 staining indicating that IFI16 is aberrantly expressed also in lymphocytes, fibroblasts, and endothelial cells. Similarly, we and others have also recently demonstrated that IFI16 is aberrantly expressed in the intestinal mucosa of patients affected by IBD, where dysregulation of host–microbial interactions has been shown to play a major pathogenic role ( 153 , 154 ). In addition, we and others have evaluated the etiopathogenic role of PYHIN proteins in the development of SLE in human pathology as well as in mouse models (Table 1 ).…”

Section: Novel Functions For Ifi16 To Trigger Inflammationsupporting

confidence: 63%

The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes

Caneparo

Landolfo²,

Gariglio

et al. 2018

Front. Immunol.

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Absent in melanoma 2 (AIM2)-like receptors (ALRs) are a newly characterized class of pathogen recognition receptors (PRRs) involved in cytosolic and nuclear pathogen DNA recognition. In recent years, two ALR family members, the interferon (IFN)-inducible protein 16 (IFI16) and AIM2, have been linked to the pathogenesis of various autoimmune diseases, among which systemic lupus erythematosus (SLE) has recently gained increasing attention. SLE patients are indeed often characterized by constitutively high serum IFN levels and increased expression of IFN-stimulated genes due to an abnormal response to pathogens and/or incorrect self-DNA recognition process. Consistently, we and others have shown that IFI16 is overexpressed in a wide range of autoimmune diseases where it triggers production of specific autoantibodies. In addition, evidence from mouse models supports a model whereby ALRs are required for IFN-mediated host response to both exogenous and endogenous DNA. Following interaction with cytoplasmic or nuclear nucleic acids, ALRs can form a functional inflammasome through association with the adaptor ASC [apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD)] and with procaspase-1. Importantly, inflammasome-mediated upregulation of IL-1β and IL-18 production positively correlates with SLE disease severity. Therefore, targeting ALR sensors and their downstream pathways represents a promising alternative therapeutic approach for SLE and other systemic autoimmune diseases.

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“…Anti-OmpC positivity was associated with a lack of response to anti-TNF therapy at 1 year and increased likelihood of therapy discontinuation in UC patients ( 73 ). Low baseline levels of IgG antibodies against the pattern recognition receptors IFI16 were associated with clinical response to infliximab induction treatment in UC ( 74 ). Several studies tested the capacity of the serological marker perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) to predict response to anti-TNF agents.…”

Section: Patient and Disease Related Predictors To Anti-tnf Therapymentioning

confidence: 99%

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

2020

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The advent of anti-TNF agents as the first approved targeted therapy in the treatment of inflammatory bowel disease (IBD) patients has made a major impact on our existing therapeutic algorithms. They have not only been approved for induction and maintenance treatment in IBD patients, but have also enabled us to define and achieve novel therapeutic outcomes, such as combination of clinical symptom control and endoscopic remission, as well as mucosal healing. Nevertheless, approximately one third of treated patients do not respond to initiated anti-TNF therapy and these treatments are associated with sometimes severe systemic side-effects. There is therefore the currently unmet clinical need do establish predictive markers of response to identify the subgroup of IBD patients, that have a heightened probability of response. There have so far been approaches from different fields of IBD research, to descry markers that would empower us to apply TNF-inhibitors in a more rational manner. These markers encompass findings from disease-related and clinical factors, pharmacokinetics, biochemical markers, blood and stool derived parameters, pharmacogenomics, microbial species, metabolic compounds, and mucosal factors. Furthermore, changes in the intestinal immune cell composition in response to therapeutic pressure of anti-TNF treatment have recently been implicated in the process of molecular resistance to these drugs. Insights into factors that determine resistance to anti-TNF therapy give reasonable hope, that a more targeted approach can then be utilized in these non-responders. Here, IL-23 could be identified as one of the key factors determining resistance to TNF-inhibitors. Growing insights into the molecular mechanism of action of TNF-inhibitors might also enable us to derive critical molecular markers that not only mediate the clinical effects of anti-TNF therapy, but which level of expression might also correlate with its therapeutic efficacy. In this narrative review, we present an overview of currently identified possible predictive markers for successful anti-TNF therapy and discuss identified molecular pathways that drive resistance to these substances. We will also point out the necessity and difficulty of developing and validating a diagnostic marker concerning clinically relevant outcome parameters, before they can finally enter daily clinical practice and enable a more personalized therapeutic approach.

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Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy

Cited by 27 publications

References 57 publications

Common Differences: The Ability of Inflammasomes to Distinguish Between Self and Pathogen Nucleic Acids During Infection

Common Differences: The Ability of Inflammasomes to Distinguish Between Self and Pathogen Nucleic Acids During Infection

The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes

Personalizing Treatment in IBD: Hype or Reality in 2020? Can We Predict Response to Anti-TNF?

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