Modulation of proinflammatory but not regulatory cytokines by in vitro JAK inhibition in peripheral blood B-cells of patients with psoriatic arthritis.

Aberrations in T-Cell Subpopulations in Patients with Psoriasis and Psoriatic Arthritis

BackgroundGuselkumab is a human IgG1λ monoclonal antibody that binds to interleukin 23, a regulatory cytokine that modifies the activity of T lymphocytes, intervening in pathogenic ways that initiate and maintain...

BackgroundPsoriatic arthritis is a chronic immune-mediated disease that mainly affect joints, but is associated with a significant increase in cardiovascular risk and other comorbidities. In the last decades, some pathogenic...

P169 Effect of macrophage migration inhibitory factor on human macrophages from arthritis patients

Background:Immunological dysregulation constitutes the primary pathogenic mechanism in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). However, these conditions exhibit distinct differences at the histopathological and clinical levels. A specific subset...

Psoriatic arthritis is a chronic progressive systemic inflammatory disease of joints and spine, which leads to the development of erosive arthritis, bone resorbtion, multiple enthesitis and spondylitis. Severe clinical course, resistance to therapy, high prevalence of disability, increased mortality of patients determine a need for further study of the disease. Psoriatic arthritis is a multifactorial disease including immune pathogenic factors representing a complex process of interaction between cellular and humoral components of immune system. The most important way of activating epidermal cells and synovial membrane proliferation in psoriatic arthritis is an imbalance of proinflammatory and anti-inflammatory cytokines. It is noted that the features of clinical course in psoriasis are age-dependent. The study of immune response indices in different age groups allows to reveal distinct progression features of the psoriatic pathology.The purpose of this study was to compare concentrations of proinflammatory and anti-inflammatory cytokines, cellular and humoral immunity, and to conduct a comparative analysis in young and adult patients with psoriatic arthritis.The study included a group of patients with psoriatic arthritis (n = 101) who were divided by their age: group 1, from 18 to 44 years (n = 43); group 2, over 44 years (n = 58). The control groups (3 and 4) included virtually healthy people (n = 103) matched for sex and age with the patients. Populational and subpopulation profiling of blood lymphocytes was performed by flow-cytometry using monoclonal antibodies to CD3, CD4, CD8, CD16, CD19 (LLC “Sorbent”, Moscow, Russia). Phagocytic activity of peripheral blood neutrophils was assessed microscopically by uptake of latex particles. Concentrations of IgA, IgM, and IgG immunoglobulins, circulating immune complexes, cytokines (IL-4, IL-6, IL-10, TNFα) in blood serum was determined by enzyme-linked immunosorbent assay. Statistical evaluation of the results obtained was performed using applied “Statistica 6.0” software.In all the age subgroups of patients with psoriatic arthritis, we have revealedstatistically significant differences against controls, i.e., increased relative and absolute number of CD3-CD16+lymphocytes in peripheral blood, higher concentration of CIC-C1q, with decreased concentrations of IgA, IgM, IgG in blood serum. The analysis of the main cellular and humoral indicators of immunity in psoriatic arthritis patients revealed a statistically significant differences for psoriatic arthritis in young and adulthood. E.g., the serum concentration of IL- 10 was statistically significantly lower in psoriatic arthritis at a young age in comparison with adult psoriatic arthritis. Phagocytic number and IgG concentration in serum were statistically significantly lower in adults with psoriatic arthritis adulthood than in young patients.In conclusion, The revealed changes in immunological indices in psoriatic arthritis in young and adult patients indicate to differences against healthy controls, as well as intergroup differences. Previous studies have not revealed statistically any significant differences in immunological parameters between young and adult patients with psoriatic arthritis in, thus suggesting a presence of immune disorders associated with psoriatic pathology, but not with the age of patients. However, changes of immunological reactivity are observed with increasing age of patients with psoriatic arthritis and development of severe clinical forms, and they can be considered as markers of psoriatic disease progression, such as increased concentrations of IL-10 and lower IgG amounts in blood serum, a decreased phagocytic number.

Background:The pathogenesis of psoriatic arthritis (PsA) is characterized by a predominant IL-17 signature. Innate-like lymphocytes, such as mucosal-associated invariant T cells (MAIT), are recognized sources of IL-17 in PsA.Objectives:1.To investigate...

INTRODUCTION: Secukinumab is an anti-IL 17A monoclonal antibody currently used to treat psoriasis, ankylosing spondylitis, and psoriatic arthritis. It may induce inflammation in the GI tract causing exacerbation of IBD and rarely causing IBD de novo. This phenomenon itself is seldom documented with only a handful of case reports in the US and overseas. The few cases of psoriatic arthritis and Secukinumab- induced UC were managed successfully with infliximab. However, there have been no case reports managing patients refractory to TNF-alpha inhibitors. This case illustrates an alternative therapy for management of Secukinumab- induced UC who have previously failed anti-TNF treatment for psoriatic arthritis. CASE DESCRIPTION: A 52-year-old female with a past history of psoriatic arthritis on Secukinumab presented with one-month history of bloody diarrhea. Colonoscopy showed diffuse ulcerative colitis (UC) from hepatic flexure to rectum. Biopsies showed crypt abscesses consistent with inflammatory bowel disease (IBD) along with a positive serum p-ANCA. The patient had no prior history of ulcerative colitis with a negative screening colonoscopy 2 years ago. Stool studies were negative for infection and biopsies were negative for CMV colitis. CT Scan of Abdomen and Pelvis showed no small intestinal disease. This patient had failed prior treatment for her psoriatic arthritis with Etanercept, Leflunomide, Adalimumab and Methotrexate. Secukinumab was discontinued and the patient was started on prednisone 40 mg po daily along with mesalamine 4.8 gm po daily. She improved and was discharged home. Later, she was started on Tofacitinib 10mg po bid to treat both psoriatic arthritis and ulcerative colitis to allow prednisone taper. The patient continued to improve with resolution of the bloody diarrhea along with symptomatic and objective improvement of her psoriatic arthritis. DISCUSSION: There have been case reports of Ulcerative Colitis developing in patients being treated with Secukinumab for psoriatic arthritis and Ankylosing Spondylitis. During phase three clinical trials of Secukinumab, only two patients, 0.058% of the subject population, on Secukinumab developed new onset IBD. In case reports of Secukinumab induced- UC, patients were successfully treated with the monoclonal TNF-alpha antibody, infliximab. However, in this case, the patient had already failed prior therapy with a monoclonal TNF-alpha antibody, Adalimumab, and a soluble TNF decoy receptor, Etanercept. Given her resistance to multiple forms of TNF-alpha inhibition, she was started on Tofacitinib, an inhibitor of JAK1 and JAK2 kinase, approved for both psoriatic arthritis and ulcerative colitis. There are no documented case reports treating both these conditions that are refractory to other biologics. In this subset of rare patients, this case illustrates a novel approach of using Tofacitinib in achieving therapeutic response for both psoriatic arthritis and ulcerative colitis.

IntroductionThe aim of this study was to characterize interleukin 17 (IL-17) and interleukin 22 (IL-22) producing cells in peripheral blood (PB), skin, synovial fluid (SF) and synovial tissue (ST) in patients with psoriasis (Ps) and psoriatic arthritis (PsA).MethodsFlow cytometry was used to enumerate cells making IL-22 and IL-17, in skin and/or SF and PB from 11 patients with Ps and 12 patients with PsA; skin and PB of 15 healthy controls and SF from rheumatoid arthritis (RA) patients were used as controls. Expression of the interleukin 23 receptor (IL-23R) and chemokine receptors CCR4 and CCR6 was examined. Secretion of IL-17 and IL-22 was measured by ELISA. ST was analysed by immunohistochemical staining of IL-17 and IL-22.ResultsIncreased frequencies of IL-17+ and IL-22+ CD4+ T cells were seen in PB of patients with PsA and Ps. IL-17 secretion was significantly elevated in both PsA and Ps, whilst IL-22 secretion was higher in PsA compared to Ps and healthy controls. A higher proportion of the CD4+ cells making IL-17 or IL-22 expressed IL-23R and frequencies of IL-17+, CCR6+ and CCR4+ T cells were elevated in patients with Ps and those with PsA. In patients with PsA, CCR6+ and IL-23R + T cells numbers were elevated in SF compared to PB. Increased frequencies of IL-17+ and IL-22+ CD4+ T cells were demonstrated in Ps skin lesions. In contrast, whilst elevated frequencies of CD4+ IL-17+ cells were seen in PsA SF compared to PB, frequencies of CD4+ IL-22+ T cells were lower. Whereas IL-17 expression was equivalent in PsA, osteoarthritis (OA) and RA ST, IL-22 expression was higher in RA than either OA or PsA ST, in which IL-22 was strikingly absent.ConclusionsElevated frequencies of IL-17 and IL-22 producing CD4+ T cells were a feature of both Ps and PsA. However their differing distribution at disease sites, including lower frequencies of IL-22+ CD4+ T cells in SF compared to skin and PB, and lack of IL-22 expression in ST suggests that Th17 and Th22 cells have common, as well as divergent roles in the pathogenesis of Ps and PsA.

Circulating Mir-140 and leptin improve the accuracy of the differential diagnosis between psoriatic arthritis and rheumatoid arthritis: a case-control study

SAT0024 Il-36 axis is an emerging therapeutic target in psoriatic arthritis synovial tissue

THU0011 CD32+ B Lymphocytes and IL21R+ T Lymphocytes Are Associated with Disease Activity and Increased Levels of Proinflammatory Cytokines in Patients with Rheumatoid and Psoriatic Arthritis

It would be interesting to acquire knowledge about predictive factors of good clinical response for each of these treatments. This would allow a more accurate decision on treatment initiation and a trend to personalized medicine. This may be achieved by retrospectively analyzing the data of randomized controlled trials and their extensions, as well as those from real-life cohorts.

Introduction. Psoriatic arthritis is a common inflammatory disease affecting the joints and it is usually accompanied by plaque psoriasis. The pathogenetic link between psoriasis and psoriatic arthritis well reflects the mechanistic hypotheses of disease pathogenesis. Psoriatic arthritis is characterized by chronic inflammation which results in bone erosion and bone loss, as well as new bone formation around the affected joints. The exaggerated inflammatory response leads to enthesitis with the crucial contribution of IL-17 producing T cells and entheseal resident cells, expressing IL-23R. Studying the IL-17 gene expression patterns can help choose a therapy for patients with psoriatic arthritis.Aim. To study alterations in IL-17 gene expression in immune cells of paediatric patients with psoriatic arthritis.Materials and methods. Mono nuclear cells were isolated from the peripheral blood of 45 patients with psoriatic arthritis and 20 healthy controls. The IL-17 gene expression was analysed using a real-time PCR.Results and discussion. Mononuclear cells were isolated from whole peripheral blood for subsequent analysis of IL-17 gene expression by quantitative RT-PCR. The comparative analysis of the expression levels of patients with psoriatic arthritis and healthy volunteers showed that the expression level of IL-17 gene in patients with psoriatic arthritis was 345 times higher than the expression level in healthy volunteers.Conclusion. Patients with psoriatic arthritis are characterized by a very high level of IL-17 gene expression in immune blood cells. The high IL-17 gene expression level confirms its significant role in the inflammatory process in patients with psoriatic arthritis.

BackgroundT cells play a major pathogenic role in Rheumatoid Arthritis (RA). Their pro-inflammatory potential, interaction with B-cells (CD4) and cytotoxic capacities (CD8) have a high impact on disease progression, at...