The Th17 Pathway in Vascular Inflammation: Culprit or Consort?
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Abstract:
The involvement of IL-17A in autoimmune and inflammatory diseases has prompted the development of therapeutic strategies to block the Th17 pathway. Promising results came from their use in psoriasis and in ankylosing spondylitis. IL-17A acts on various cell types and has both local and systemic effects. Considering the premature mortality observed during chronic inflammatory diseases, IL-17A action on vascular cells was studied. Both in vitro and in vivo results suggest that this cytokine favors inflammation, coagulation and thrombosis and promotes the occurrence of cardiovascular events. These observations led to study the role of IL-17A in diseases characterized by vascular inflammation, namely allograft rejection and vasculitis. Increased circulating levels of IL-17A and histological staining reveal that the Th17 pathway is involved in the pathogenesis of these diseases. Vasculitis treatment faces challenges while the use of steroids has many side effects. Regarding results obtained in giant cell arteritis with IL-6 inhibitors, a cytokine involved in Th17 differentiation, the use of anti-IL-17 is a promising strategy. However, lessons from rheumatoid arthritis and multiple sclerosis must be learnt before targeting IL-17 in vasculitis, which may be culprit, consort or both of them.Keywords:
Pathogenesis
Ankylosing spondylitis is apparently rare among Japanese and it is known that this disease is commoner in males than in females. The male to female ratio among general ankylosing spondylitis is 4.5:1. The cardiac conduction abnormalities, aortic insufficiency and mitral insufficiency are sometimes associated with this disease. We analysed the influence of sex on the development of these cardiac complications using 95 reported cases of ankylosing spondylitis including our case. Among the ankylosing spondylitis patients who were accompanied with cardiac complication, 99% were male. This frequency is significantly high compared with that found in general ankylosing spondylitis (p less than 0.0001). The cardiac complication associated with this disease seems to be characteristic for males. This sex difference is useful for differential diagnosis from various diseases which accompany these cardiac complications. The mechanism of sex influence on the cardiac complication of ankylosing spondylitis was also discussed.
Spondylitis
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Objective:To explore the role of Platelet parameters(PLT、MPV) in activity ankylosing spondylitis,Discusses the mechanism and clinical value.Methods:by the whole blood cells analyser and immunology detection methods,detected the Venous blood platelets parameter(PLT、MPV)and CRP of 53 cases activity ankylosing spondylitis and 39 cases Health group,And do statistical analysis.Results:the CRP and PLT of activity ankylosing spondylitis are Significantly higher than health group,MPV significantly smaller than healthy group(P =0.000,P0.05),there is positively correlated between PLT and CRP(r=0.421,P0.05),MPV and CRP(r=-0.325,P0.05),negative correlation exists.Conclusion:Platelet parameters(PLT,MPV)have relations with the activity ankylosing spondylitis disease,Can be used as a reaction index condition monitoring.And as the same important role of CRP.
Spondylitis
Mean platelet volume
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Outcome measurement in spondylarthritis, particularly
ankylosing spondylitis (AS) has been a rapidly growing
field over the last decade, with enormous progress being
made in patient-reported outcomes, clinical assessments,
physical measurements and composite scoring of disease
state, and response to treatment. Many of these advances
arose out of need, when anti–tumor necrosis factor therapies
were found to have a role in the treatment of AS
patients and therefore required appropriate clinical assessment.
The Assessment of SpondyloArthritis international
Society (ASAS) was first formed in 1995 as a group of
clinicians and methodologists with a shared interest in
outcome measurement in AS patients, and has grown to
incorporate early diagnosis, classification, development
and validation of outcome measures, and evaluation of
therapeutic modalities.
The instruments reviewed here include those recommended
in the ASAS core sets for clinical record keeping
(in daily clinical practice) and for clinical research, as over
time these have been extensively validated and implemented
across different clinical settings. The core sets
describe those health-related domains that should be
measured in AS patients in different settings, and recommend
appropriate instruments that can be used for that
domain. Additional measures included are the AS Quality
of Life scale and the Health Assessment Questionnaire for
the Spondylarthropathies, which cover health domains
not included in the original core sets but have been shown
to be important to AS patients through the World Health
Organization International Classification of Functioning,
Disability and Health projects (1). Finally, the AS Disease
Activity Score has also been presented, as an alternative to
the Bath Ankylosing Spondylitis Disease Activity Index,
as one of the newest measures constructed to assess disease
activity.
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Pathogenesis
Interleukin 22
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Introduction: T-helper 1 (Th1), Th17 cells, and their related cytokines are implicated in psoriasis pathogenesis although the contribution of each group of cytokines in psoriasis activity has not been fully clarified. Objectives: To investigate whether Th17-related cytokines are associated with psoriasis activity. Methods: The serum levels of interleukin (IL)-1β, 6, 8, 17Α, 22, 23, and tumor necrosis factor-α (TNFα) were measured with flow cytometry in 35 patients with plaque psoriasis (21 with stable and 14 with active disease) and in 20 healthy controls. Results: Interleukin-6, 8, 17A, 22, 23, and TNFα were significantly elevated in psoriasis patients compared with controls. In the sensitivity analyses, patients with active disease showed significantly increased levels of IL-17A, IL-23, and IL-22 as compared to the group of patients with stable psoriasis. Conclusions: Our study highlights a possible crucial role of IL-17A, IL-22, and IL-23 in the activity of psoriasis and the early stages of the disease.
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Interleukin-23
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To examine the serum levels of interleukin (IL)-30 in patients with psoriasis and evaluate the correlations with the Psoriasis Area and Severity Index (PASI).Serum was collected from 26 patients with psoriasis and 26 healthy controls in a case-control setting, and the level of IL-30 was determined using an enzyme-linked immunosorbent assay. Statistical analysis of the IL-30 levels among groups and further correlation analyses of IL-30 levels with PASI scores were performed.A significant increase in the level of IL-30 in patients with psoriasis compared with healthy controls was observed. In addition, a positive correlation between the IL-30 concentration and PASI scores was found in patients with psoriasis.IL-30 is presumably involved in the proliferation of epidermal cells during the development of psoriasis. Further studies with a larger number of participants are required to comprehensively elucidate the biological roles of IL-30 in the pathogenesis of psoriasis.
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Positive correlation
Interleukin 22
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This chapter contains sections titled: Introduction History of psoriasis Who gets psoriasis? Biology of psoriasis Comorbidities associated with psoriasis Clinical variants of psoriasis Physical symptoms that accompany psoriasis Trigger factors in psoriasis Treatments for psoriasis Measuring quality of life Conclusion References
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Psoriasis is a multifactor skin disorder, with immune-mediated inflammatory pathogenesis. Theories and studies illustrated the crucial role for Interleukin-17 (IL-17) in promotes the occurrence and severity of psoriasis. We measured the serum IL-17 levels for detection the importance and effects of IL-17 as predictors for the psoriasis disorders and its severity. Forty-five cases of psoriatic patients and the same number from healthy subjects as control were included in this study, the severity of psoriasis was determined by the Psoriasis Area and Severity Index (PASI). Patients were categorize according to severity as mild psoriasis in (21), and moderate to severe psoriasis group in (24), 3 ml sera samples of both groups were collected to estimate IL-17, The results showed that the majority of the patients comprised of age group 36-45 (42.0%), Female to male ratio in patients was 1.6:1. Serum IL-17 was significantly increasing among psoriatic patients as compared to healthy controls (895.066 pg/ml and 364.334 pg/ml) respectively. Also, there was a relation between an elevated IL-17 serum levels and Psoriasis severity of groups with highly significant difference. It can be concluded that (IL-17) has important role during the activity of psoriasis and should be a target for biological therapy in Iraqi psoriatic patients.
Pathogenesis
Interleukin 22
Interleukin-23
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