scholarly journals The IL-17/IL-23 Axis and Its Genetic Contribution to Psoriatic Arthritis

2021 ◽  
Vol 11 ◽  
Author(s):  
Matteo Vecellio ◽  
Vivien Xanath Hake ◽  
Connor Davidson ◽  
Maria Cristina Carena ◽  
B. Paul Wordsworth ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Monozygotic Twins ◽  
Cell Types ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Nucleotide Polymorphisms ◽  
Biologic Drugs ◽  
Skeletal Involvement ◽  
The Family ◽  
Genetic Stratification

Psoriatic arthritis (PsA) is a chronic inflammatory disease belonging to the family of spondyloarthropathies (SpA). PsA commonly aggravates psoriasis of the skin and frequently manifests as an oligoarthritis with axial skeletal involvement and extraarticular manifestations including dactylitis, enthesitis, and uveitis. The weight of genetic predisposition to psoriasis and PsA is illustrated by the concordance rates in monozygotic twins which clearly demonstrate that genomics is insufficient to induce the clinical phenotype. The association of PsA with several single nucleotide polymorphisms (SNPs) at the IL23R locus and the involvement of Th17 cells in the immunopathogenesis of PsA clearly put the IL-23/IL-17 axis in the spotlight. The IL-23 and IL-17 cytokines have a pivotal role in the chronic inflammation of the synovium in PsA and are also prominent in the skin lesions of those with PsA. In this review, we focus on the genetic association of the IL-23/IL-17 axis with PsA and the contribution of these master cytokines in the pathophysiology of the disease, highlighting the main cell types incriminated in PsA and their specific role in the peripheral blood, lesional skin and joints of patients. We then provide an overview of the approved biologic drugs targeting the IL-23/IL-17 axis and discuss the advantages of genetic stratification to enhance personalized therapies in PsA.

Ustekinumab-induced Sarcoidosis in a Patient with Psoriatic Arthritis

2020 ◽  
Vol 15 (2) ◽  
pp. 163-166 ◽  
Author(s):  
Senol Kobak ◽  
Huseyin Semiz
Keyword(s):  
Psoriatic Arthritis ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Acute Phase Reactants ◽  
Caseating Granuloma ◽  
Endobronchial Ultrasonography ◽  
Chest X Ray ◽  
Dose Corticosteroid ◽  
One Year

Background: Psoriatic Arthritis (PsA) is a chronic inflammatory disease that may affect different joints. Sarcoidosis is a Th-1 cell-related chronic granulomatous disease characterized by non-caseating granuloma formation. The coexistence of both the diseases is a rare entity. Ustekinumab, an IL12 / 23 inhibitor, has shown efficacy and safety in the treatment of PsA. Objective: This study presents a case with ustekinumab-induced sarcoidosis in a patient with PsA. Case Report: A 52 years old female patient with complaints of pain and swelling of the wrists, MCP, PIP and DIP joints and skin lesions was referred to our Rheumatology clinic. On her medical history, she had been under follow up for 5 years with the diagnosis of psoriasis and one year ago, she started to receive ustekinumab prescribed by a dermatologist. On physical examination, she had psoriasis skin lesions and arthritis of both wrists, MCP, PIP, DIP joints. Bilateral hilar lymphadenopathies were detected in the chest X-ray and thorax computed tomography. In laboratory tests, acute phase reactants and serum angiotensin-converting enzyme levels were high. Endobronchial ultrasonography biopsy was performed and non-caseating granuloma consistent with sarcoidosis was reported. Ustekinumab was discontinued, methotrexate and low-dose corticosteroid were started. The patient was clinically stable in the 6th month of the treatment and the findings were regressed. Conclusion: Sarcoidosis development appears to be a new paradoxical effect of ustekinumab therapy, being another biological agent.

scholarly journals Psoriatic onycho-pachydermo-periostitis / Psoriatični onihopahidermoperiostitis

2010 ◽  
Vol 2 (2) ◽  
pp. 54-58
Author(s):  
Zorica Perić-Hajzler ◽  
Lidija Kandolf-Sekulović ◽  
Lidija Zolotarevski
Keyword(s):  
Psoriatic Arthritis ◽  
Antibody Therapy ◽  
Skin Lesions ◽  
Treatment Modalities ◽  
Psoriatic Skin ◽  
Symptom Improvement ◽  
Nail Changes ◽  
The Family ◽  
History Of ◽  
Inflammatory Drugs

Abstract Psoriatic onycho-pachydermo-periostitis has been recognized as an uncommon subset of psoriatic arthritis, and to date, only a few cases have been reported. In general, psoriatic onycho-pachydermo-periostitis is regarded as a unique variant of psoriatic arthritis, but its pathology and pathophysiology are not well understood. Although psoriatic onychopachydermo- periostitis is usually found in patients with psoriasis, it can also be found in patients without psoriatic skin lesions. It is characterized by psoriatic nail changes (usually onycholysis), painful swelling of the soft tissue close to the distal phalanges, and radiographic changes of the distal phalanges with periosteal reaction and bone erosions. We present a 58-year-old man with a 3-year history of deformation, thickened nails and pustules on the skin of his fingers and toes, and painful redness of the nail bed accompanied with pain in small joints. The family history was negative. After confirmation of the diagnosis, methotrexate: 15 mg weekly, was initiated which led to symptoms improvement. Treatment of psoriatic onycho-pachydermo-periostitis is difficult. It is based on treatment modalities used for other forms of psoriatic arthritis, such as sulphasalazine, methotrexate, and anti-tumor necrosis factor antibody therapy with adalimumab and etanercept. Nonsteroidal anti-inflammatory drugs are usually ineffective. Retinoids, subungual cyclosporine and corticosteroid therapy also showed inefficient. In our patient, methotrexate has shown efficacy in symptom improvement.

scholarly journals A CLINICO-EPIDEMIOLOGICAL STUDY OF PSORIASIS IN A TERTIARY CARE HOSPITAL IN PATNA, BIHAR

2020 ◽  
pp. 53-54
Author(s):  
Vikas Shankar ◽  
Alok Kumar ◽  
Manadavi Manadavi ◽  
Ayushi Ayushi ◽  
Debarshi Jana
Keyword(s):  
Crohn’S Disease ◽  
Psoriatic Arthritis ◽  
Crohn's Disease ◽  
Tertiary Care ◽  
Skin Lesions ◽  
Tertiary Hospital ◽  
Chronic Inflammatory Disease ◽  
Care Hospital ◽  
Cross Sectional ◽  
Co Morbidity

Background: Psoriasis is a chronic inflammatory disease most commonly manifested by skin lesions on the elbows, knees, scalp, genitals, and trunk. The co-morbidities more commonly associated to psoriasis include psoriatic arthritis (PsA) and Crohn’s disease, others being hyperlipidemia, diabetes mellitus, arterial hypertension, rheumatoid arthritis, obesity, ischemic heart disease, ulcerative colitis, reduced quality of life, depression and malignancy. Present study aims to study the prevalence of co- morbidity factors associated with psoriasis. Materials and methods: A hospital based cross sectional study was conducted in Dermatology outpatient department at a tertiary hospital in Patna, Bihar. Written informed consent was taken from the patients. Detailed clinical evaluation and relevant investigations were done for all patients. Data was analysed using SPSS software ver. 17. Results: A total of 86 psoriasis patients were included in the study. Male pre-dominance (65%) was observed with majority of patients were between 30-50 years of age. Psoriasis was associated with a significantly increased prevalence for hypertension (46.51%), hyperlipidemia (48.83%), diabetes (38.31%), cardiovascular disease (10.46%), COPD (9.30%), psoriatic arthritis (29.06%), metabolic syndrome (34.88%), Crohn’s disease (1.16%) and depression (47.67%). Conclusion: The study revealed a male preponderance with peak incidence in third and fourth decade of life. We also observed a high prevalence of associated co-morbidites in patients of psoriasis which play a major role in diasease progression and hence should be addressed accordingly.

Nuclear receptors in disease: the oestrogen receptors

2004 ◽  
Vol 40 ◽  
pp. 157-167 ◽  
Author(s):  
Maria Nilsson ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Receptor Subtype ◽  
Target Tissue ◽  
Oestrogen Receptors ◽  
Nucleotide Polymorphisms ◽  
Cell Type ◽  
Single Nucleotide ◽  
Beneficial Effects ◽  
The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

scholarly journals De Novo SNP Discovery and Genotyping of Iranian Pimpinella Species Using ddRAD Sequencing

Agronomy ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1342
Author(s):  
Shaghayegh Mehravi ◽  
Gholam Ali Ranjbar ◽  
Ghader Mirzaghaderi ◽  
Anita Alice Severn-Ellis ◽  
Armin Scheben ◽  
...  
Keyword(s):  
De Novo ◽  
Genetic Relationships ◽  
Nucleotide Polymorphisms ◽  
High Quality ◽  
Genomic Resources ◽  
High Quality Snps ◽  
The Family ◽  
Double Digestion ◽  
Flanking Sequences ◽  
Downstream Analysis

The species of Pimpinella, one of the largest genera of the family Apiaceae, are traditionally cultivated for medicinal purposes. In this study, high-throughput double digest restriction-site associated DNA sequencing technology (ddRAD-seq) was used to identify single nucleotide polymorphisms (SNPs) in eight Pimpinella species from Iran. After double-digestion with the enzymes HpyCH4IV and HinfI, a total of 334,702,966 paired-end reads were de novo assembled into 1,270,791 loci with an average of 28.8 reads per locus. After stringent filtering, 2440 high-quality SNPs were identified for downstream analysis. Analysis of genetic relationships and population structure, based on these retained SNPs, indicated the presence of three major groups. Gene ontology and pathway analysis were determined by using comparison SNP-associated flanking sequences with a public non-redundant database. Due to the lack of genomic resources in this genus, our present study is the first report to provide high-quality SNPs in Pimpinella based on a de novo analysis pipeline using ddRAD-seq. This data will enhance the molecular knowledge of the genus Pimpinella and will provide an important source of information for breeders and the research community to enhance breeding programs and support the management of Pimpinella genomic resources.

Association of Interleukin 23 Receptor Variants with Psoriatic Arthritis

2009 ◽  
Vol 36 (1) ◽  
pp. 137-140 ◽  
Author(s):  
PROTON RAHMAN ◽  
ROBERT D. INMAN ◽  
WALTER P. MAKSYMOWYCH ◽  
JEFF P. REEVE ◽  
LYNETTE PEDDLE ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Permutation Test ◽  
Psoriatic Skin ◽  
Nucleotide Polymorphisms ◽  
Marker Haplotype ◽  
Sliding Windows ◽  
Genome Wide ◽  
Canadian Population ◽  
Interleukin 23 ◽  
Coding Snp

Objective.A recent genome-wide pooling study noted a significant association of interleukin 23 receptor (IL-23R) and psoriasis. Overxpression of IL-23 has been detected in lesional psoriatic skin, and induces epidermal proliferation. Given the interplay between psoriasis and PsA, we examined the association of IL-23R variants in 2 independent Canadian Caucasian cohorts of patients with psoriatic arthritis (PsA).Methods.We examined 496 PsA probands and 476 controls. Cases and controls were genotyped for a panel of 11 single-nucleotide polymorphisms (SNP) in IL-23R. Allele and haplotype associations were calculated using WHAP software. P values for haplotype associations were calculated using a permutation test.Results.The 381Gln allele of the coding SNP Arg381Gln (rs11209026) was found to be protective in the Canadian population (p = 0.004; corrected p = 0.044).A 2-marker haplotype from SNP rs7530511 and rs11209026 was associated with PsA (p = 0.011). All 3-marker sliding windows containing SNP rs11209026 were associated with PsA (p = 0.02 for all 3 windows). The magnitude of effect of IL-23R association in PsA appears to be similar to that reported in uncomplicated psoriasis.Conclusion.Significant associations between Arg381Gln SNP and haplotypes encoding this variant were noted in PsA. It remains to be determined what contribution of this association, if any, is specifically due to the inflammatory arthritis (PsA) rather than psoriasis.

scholarly journals Mechanisms in allergic airway inflammation – lessons from studies in the mouse

2008 ◽  
Vol 10 ◽  
Author(s):  
Bennett O.V. Shum ◽  
Michael S. Rolph ◽  
William A. Sewell
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Cellular Response ◽  
Allergic Airway Inflammation ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Chronic Inflammatory Disease ◽  
Pathological Feature ◽  
Cytokines And Chemokines ◽  
Novel Therapeutic

Asthma is a chronic inflammatory disease of the airways, involving recurrent episodes of airway obstruction and wheezing. A common pathological feature in asthma is the presence of a characteristic allergic airway inflammatory response involving extensive leukocyte infiltration, mucus overproduction and airway hyper-reactivity. The pathogenesis of allergic airway inflammation is complex, involving multiple cell types such as T helper 2 cells, regulatory T cells, eosinophils, dendritic cells, mast cells, and parenchymal cells of the lung. The cellular response in allergic airway inflammation is controlled by a broad range of bioactive mediators, including IgE, cytokines and chemokines. The asthmatic allergic inflammatory response has been a particular focus of efforts to develop novel therapeutic agents. Animal models are widely used to investigate inflammatory mechanisms. Although these models are not perfect replicas of clinical asthma, such studies have led to the development of numerous novel therapeutic agents, of which some have already been successful in clinical trials.

scholarly journals Could Chlamydia Pneumoniae Be Considered an Infectious Risk Factor for Inflammatory Diseases Such as Atherosclerosis ?

2005 ◽  
Vol 3 (3) ◽  
pp. 109-112
Author(s):  
R. Sessa ◽  
M. Di Pietro ◽  
G. Schiavoni ◽  
I. Santino ◽  
M. Del Piano
Keyword(s):  
Risk Factor ◽  
Chlamydia Pneumoniae ◽  
Direct Detection ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Chronic Inflammatory Disease ◽  
Upper Respiratory Tract ◽  
Infectious Risk ◽  
Tract Infections

Chlamydia pneumoniae, a Gram-negative intracellular obligate bacteria, is recognised as a common cause of upper respiratory tract infections, and accounts for ∼10% of community-acquired pneumonia. In recent years, chronic and persistent infection with C. pneumoniae has been implicated in the pathogenesis of atherosclerosis. Atherosclerosis is regarded as a chronic inflammatory disease that results from complex interactions between a variety of cell types such as endothelial cells, vascular smooth muscle cells, monocytes/macrophages and inflammatory mediators. Involvement of C. pneumoniae in the pathogenesis of atherosclerosis has been supported by findings from seroepidemiologic studies, direct detection of chlamydial DNA, experimental animal and in vitro studies, and antibiotic intervention trials. The spectrum of cell biological, animal, and human clinical data suggests that C. pneumoniae may be considered an infectious risk factor for atherosclerosis but further studies are needed to clarify the etiopathogenetic role of C. pneumoniae in atherosclerotic vessel walls.

The SNP rs560426 Within ABCA4-ARHGAP29 Locus and the Risk of Nonsyndromic Oral Clefts

2020 ◽  
Vol 57 (6) ◽  
pp. 671-677 ◽  
Author(s):  
Yah-Huei Wu-Chou ◽  
Kuo-Ting Philip Chen ◽  
Yi-Chieh Lu ◽  
Yin-Ting Lin ◽  
Hsien-Fang Chang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Strong Association ◽  
Nucleotide Polymorphisms ◽  
Test Analysis ◽  
Oral Clefts ◽  
The Family ◽  
Abca4 Gene ◽  
Family Based ◽  
New Evidence

Objective: Nonsyndromic oral clefts are common birth defect with complex etiology. In the present study, we attempt to further validate the possible role for ABCA4 and ARHGAP29 in the susceptibility to nonsyndromic oral clefts. Design: We performed allelic transmission disequilibrium test analysis, on 10 eligible single nucleotide polymorphisms (SNPs) and SNP haplotypes using the Family-Based Association Test. Participants: The study sample consisted of 334 case–parent trios of nonsyndromic oral clefts from Taiwanese population, separated into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO) groups. Results: We found only the SNP rs560426 within the ABCA4 gene showed strong association with NSCPO ( P = .03498; Permuted P = .05382). No association between other 9 selected SNPs in ABCA4-ARHGAP29 region and the risk of nonsyndromic oral clefts was found. For the haplotype analyses, we found only haplotype T-C (rs570926 and rs3789431) in ABCA4 block 2 showed significant association with nonsyndromic NSCL/P in these Taiwanese trios. Conclusions: We used a family-based analysis in 334 Taiwanese case–parent trios to validate the possible role for ABCA4 and ARHGAP29 in the susceptibility to nonsyndromic oral clefts. This study provides a new evidence for an association between the intron variant rs560426 within ABCA4 and nonsyndromic cleft palate which may contribute their regulatory role in craniofacial development.

scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

2021 ◽  
Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Experimental Verification ◽  
Inflammatory Disease ◽  
Therapeutic Target ◽  
Tyrosine Phosphatase ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Potential Therapeutic Target ◽  
Single Cell Rna Sequencing

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

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