Clinical Consequences of Targeting IL-17 and TH17 in Autoimmune and Allergic Disorders

Robinson, Keven M.; Manni, Michelle L.; Biswas, Partha S.; Alcorn, John F.

doi:10.1007/s11882-013-0361-0

Cited by 35 publications

(32 citation statements)

References 98 publications

(84 reference statements)

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“…13 The importance of Th17 cells that are involved in chronic inflammation, such as IL-17, which is present in both asthma and systemic diseases, including multiple sclerosis, systemic lupus erythematosus and others, has been discussed recently. 14,15 Data indicating that SIT might trigger the development of some autoimmune diseases, such as scleroderma, systemic vasculitis, multiple sclerosis and others, have been based on only a few reports. 4,[7][8][9][10][11] In addition, these diseases are relative contraindications for SIT in many international guidelines; however, there are no recommendations to preclude active patients with these diseases before SIT if they do not have any clinical disease symptoms.…”

Section: Discussionmentioning

confidence: 99%

The relationship between autoimmunity and specific immunotherapy for allergic diseases

Bożek

Kołodziejczyk²,

Bednarski

2015

Human Vaccines & Immunotherapeutics

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The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1 §12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this longterm observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term.

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Section: Discussionmentioning

confidence: 99%

The relationship between autoimmunity and specific immunotherapy for allergic diseases

Bożek

Kołodziejczyk²,

Bednarski

2015

Human Vaccines & Immunotherapeutics

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“…The pooled estimates for candida infections were however higher compared to placebo but the CIs were wide and included the null value. It must be noted that given the function of the cytokines involved in this pathway combating microbial agents including parasites and fungi, the risk of infection, especially candida infection, still exists and is also more relevant for a longer-term treatment and can pose a theoretical risk similar to those of the TNF-α antagonists [27]. This meta-analysis could not evaluate the long-term safety in active PsA because of the shorter placebo-controlled duration of the trials.…”

Section: Summary Of Evidencementioning

confidence: 98%

Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Naik¹,

Ming²,

Magodoro³

et al. 2017

Dermatology

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tool was used for assessing quality. The pooled relative risk (RR) was derived from random effects models. Results: Seven randomized controlled trials were included which randomized 1,718 patients to Th17 inhibitors and 840 to placebo. Patients treated with Th17 inhibitors had an RR of 2.04 (95% CI: 1.79-2.33; p < 0.001) for achieving an ACR20 response at week 12 (I 2 = 0%; p = 0.89) compared to placebotreated patients. There was no evidence of publication bias. The result was consistent for study phase and outcome (ACR50/70), mechanism of action and TNF-α naivety. RR of infections was 1.06 (0.91-1.23), that of candida infections was 3. 35 (0.75-14.95), that of serious adverse events was 0.82 (0.42-1.59) and that of discontinuation of treatment was 0.54 (0.31-0.93) among treated versus placebo subjects. No incident cases of tuberculosis were reported. Conclusion: In patients with active PsA, biologics targeting the Th17 axis produce a clinically significant improvement in joint disease activity with acceptable safety and tolerability for short-term treatment compared to placebo. © 2017 S. Karger AG, BaselKeywords Meta-analysis · Biological therapy · Active psoriatic arthritis · Systematic review · Th17 pathway inhibitors Abstract Background: Several biologics targeting the Th17 pathway have been developed for the treatment of psoriatic arthritis (PsA), a disabling disease with moderate response and an increased incidence of serious infections to first-line biologics (TNF-α antagonists). Th17 inhibitors could replace TNF-α antagonists as first-line biologic agents. We determined the overall treatment effect of Th17 pathway inhibitors compared to placebo or active control on American College of Rheumatology (ACR) 20 response at week 12 (primary objective), risk of infections, discontinuation of treatment due to adverse events, and serious adverse events during the placebo-controlled period (12-24 weeks) in adults with active PsA in published randomized controlled trials. Methods: The SCOPUS database was searched. The Cochrane risk of bias

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“…Although IL-23 was initially thought to induce Th17 polarization, naïve Th cells do not express IL-23 receptor (IL-23R) and therefore IL-23 is not required for early Th17 differentiation [31,32]. During Th17 development, IL-6 and TGF-β1 activates IL-23R expression; and IL-23 induces STAT3 and Th17 proliferation and production of cytokines, such as IL-17 and IL-22 [27,28]. In addition to IL-17 and IL-22, Th17 cells produce IL-21 which promotes Th17 cell lineage differentiation and potentially acts as an auto feedback mechanism [33].…”

Section: Regulation Of Th17 Differentiationmentioning

confidence: 99%

“…These cells are characterized by high expression of the transcription factors retinoic acid (RA)-related orphan receptor γ thymus (RORγT) and RA-related orphan receptor α (RORα), that are critical for Th17 differentiation. Th17 cells are not only critical for host defense against extracellular pathogens, but have been implicated in the pathogenesis of a number of inflammatory diseases, including autoimmune disorders and allergic asthma [24-28]. …”

mentioning

confidence: 99%

A tale of two cytokines: IL-17 and IL-22 in asthma and infection

Manni

Robinson

Alcorn

2013

Expert Review of Respiratory Medicine

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The Th17 pathway has recently been shown to play a critical role in host defense, allergic responses and autoimmune inflammation. Th17 cells predominantly produce IL-17 and IL-22, which are two cytokines with broad effects in the lung and other tissues. This review summarizes not only what is currently known about the molecular regulation of this pathway and Th17-related cytokine signaling, but also the roles of these cytokines in pathogen immunity and asthma. In the last 5 years, the Th17 field has rapidly grown and research has revealed that the Th17 pathway is essential in lung pathogenesis in response to exogenous stimuli. As work in the field continues, it is expected that many exciting therapeutic advances will be made for a broad range of diseases.

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Clinical Consequences of Targeting IL-17 and TH17 in Autoimmune and Allergic Disorders

Cited by 35 publications

References 98 publications

The relationship between autoimmunity and specific immunotherapy for allergic diseases

The relationship between autoimmunity and specific immunotherapy for allergic diseases

Th17 Inhibitors in Active Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

A tale of two cytokines: IL-17 and IL-22 in asthma and infection

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