Autoinflammation and autoimmunity: Bridging the divide

Doria, Andrea; Zen, Margherita; Bettio, Silvano; Gatto, Mariele; Bassi, Nicola; Nalotto, Linda; Ghirardello, Anna; Iaccarino, Leonardo; Punzi, Leonardo

doi:10.1016/j.autrev.2012.07.018

Cited by 194 publications

(138 citation statements)

References 92 publications

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“…Furthermore, the inflammatory cascades activated by IL1β, can be responsible for chronic inflammation and sterile neutrophilic inflammation, which may result in arthritis, a common feature in auto-inflammatory diseases. 28,39 PG has also been associated with HIV, hepatitis, systemic lupus erythematous, PAPA syndrome and the associated syndromes (PAPASH and PASH), Takayasu's arteritis, solid tumors, and pregnancy. 23,29,33 Furthermore, drugs such as propylthiouracil, isotretinoin, pegfilgrastim, TNF inhibitors, and gefitinib have been reported to induce PG.…”

Section: Associated Diseasesmentioning

confidence: 99%

Pyoderma gangrenosum: challenges and solutions

Gameiro¹,

Pereira²,

Cardoso³

et al. 2015

OTT

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Pyoderma gangrenosum (PG) is a rare disease, but commonly related to important morbidity. PG was first assumed to be infectious, but is now considered an inflammatory neutrophilic disease, often associated with autoimmunity, and with chronic inflammatory and neoplastic diseases. Currently, many aspects of the underlying pathophysiology are not well understood, and etiology still remains unknown. PG presents as painful, single or multiple lesions, with several clinical variants, in different locations, with a non specific histology, which makes the diagnosis challenging and often delayed. In the classic ulcerative variant, characterized by ulcers with inflammatory undermined borders, a broad differential diagnosis of malignancy, infection, and vasculitis needs to be considered, making PG a diagnosis of exclusion. Moreover, there are no definitively accepted diagnostic criteria. Treatment is also challenging since, due to its rarity, clinical trials are difficult to perform, and consequently, there is no "gold standard" therapy. Patients frequently require aggressive immunosuppression, often in multidrug regimens that are not standardized. We reviewed the clinical challenges of PG in order to find helpful clues to improve diagnostic accuracy and the treatment options, namely topical care, systemic drugs, and the new emerging therapies that may reduce morbidity.

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Section: Associated Diseasesmentioning

confidence: 99%

Pyoderma gangrenosum: challenges and solutions

Gameiro¹,

Pereira²,

Cardoso³

et al. 2015

OTT

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“…Moreover, the regulatory role of macroautophagy on IL-1α and β secretion (Deretic et al, 2013) could affect several autoimmune diseases, for example, SLE, RA, vitiligo, multiple sclerosis, autoimmune Addison's disease, celiac disease and type 1 diabetes. It has to be noted, however, that a strict causal relationship between these autoimmune syndromes and IL-1β secretion is not firmly proven or remains confusing in the existing literature Doria et al, 2012).The effect of CMA activity on several human autoimmune diseases is unknown until now. Recently developed molecules targeting HSPA8 or other specific molecules of the CMA process could give new information about CMA regulation and its possible impact in certain autoimmune diseases.…”

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confidence: 99%

Pharmacological regulators of autophagy and their link with modulators of lupus disease

Gros

Muller

2014

British J Pharmacology

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Autophagy is a central regulator of cell survival. It displays both anti-and pro-death roles that are decisive in the maintenance of cell homeostasis. Initially described in several eukaryotic cellular models as being induced under nutrient stress favouring survival by energy supply, autophagy was found later to display other decisive physiological roles, especially in the immune system. Thus, it is involved in antigen presentation and lymphocyte differentiation as well as in the balance regulating survival/death and activation of lymphocytes. Autophagy therefore appears to be central in the regulation of inflammation. The observation that autophagy is deregulated in systemic lupus erythematosus is recent. This discovery revives the programme dealing with the design and development of pharmacological autophagy regulators in the therapeutic context of lupus, a debilitating autoimmune disease that affects several million people in the world. A large number of molecules that positively and negatively regulate autophagy have been described, most of them with therapeutic indications in cancer and infection. Only a few, however, are effectively potent activators or inhibitors endowed with experimentally demonstrated selective properties. In this review article, we highlight the most relevant ones and summarize what we know regarding their mechanism of action. We emphasize the link between pharmacological regulators of autophagy and inducers or inhibitors of lupus disease and discuss the fundamental and pharmacological/therapeutic interest of this functional interplay. AbbreviationsCMA, chaperone-mediated autophagy; CQ/HCQ, chloroquine/hydroxychloroquine; HSPA8/HSC70, heat shock cognate protein of 70 kDa; LAP, LC3-associated phagocytosis; LC3, microtubule-associated protein light chain 3; MHC-I/II, MHC class I or MHC class II; mTOR, mammalian target of rapamycin; PRR, pattern recognition receptors; SLE, systemic lupus erythematosus TLR 9 RapamycinThis Table lists the protein targets and ligands in this article which are hyperlinked to corresponding entries in http:// www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and the Concise Guide to PHARMACOLOGY 2013/14 (Alexander et al., 2013a). Autophagy and its implication in human diseasesAutophagy is a catabolic process related to lysosomal degradation. Opposed to heterophagy, which implies degradation of substrates from outside the cell, autophagy catabolizes the cytoplasmic content. There are three main pathways involved in autophagy. The first one, called microautophagy, involves the direct engulfment of cytosolic material into the lysosome. Its core molecular machinery and regulation as well as its possible implication in human diseases are still poorly understood. In this review, we will focus the first part of our comments on the two other types of autophagy, namely, macroautophagy and chaperone-mediated autophagy (CMA). Historically, the term 'autophagy' was proposed by Christian De Duve in the ...

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“…Although these diseases are systemic in nature, tissue destruction is the result of dysregulation of innate and adaptive immunity in specific organs, such as joints and skin. 1,2 In addition to symptoms of tissue destruction, these autoimmune diseases have substantial negative impact on health-related quality of life. [3][4][5] Several biologic therapies that target specific components of the immune system are approved by the U.S. Food and Drug Administration (FDA) for the treatment of autoimmune diseases, including agents that target tumor necrosis factor (TNF; adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab); Cluster of Differentiation (CD) 20 (rituximab); interleukin (IL)-12 and IL-23 (ustekinumab); and CD80 and CD86 (abatacept; Table 1).…”

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confidence: 99%

Treatment Patterns and Annual Drug Costs of Biologic Therapies Across Indications from the Humana Commercial Database

Howe¹,

Eyck²,

Dufour³

et al. 2014

JMCP

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BACKGROUND: A variety of biologic therapies are currently used for the treatment of inflammatory autoimmune diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). These diseases require long-term treatment, and information regarding the use and costs of biologic therapies can be valuable in making treatment and formulary decisions for clinicians and payers.

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Autoinflammation and autoimmunity: Bridging the divide

Cited by 194 publications

References 92 publications

Pyoderma gangrenosum: challenges and solutions

Pyoderma gangrenosum: challenges and solutions

Pharmacological regulators of autophagy and their link with modulators of lupus disease

Treatment Patterns and Annual Drug Costs of Biologic Therapies Across Indications from the Humana Commercial Database

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