Seronegative Spondyloarthropathies Research Articles

Metabolic Syndrome and Cardiovascular Diseases in Seronegative Spondyloarthropathy and Rheumatoid Arthritis Patients: A Comparative Study

Background: Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are ones of the most rheumatic diseases with chronic inflammatory damaging processes that have a great risk for metabolic syndrome (MS) and cardiovascular diseases. Several studies have indicated higher cardiovascular disease (CVD) risk and mortality rates among these patients compared to the general population. Objective: To identify the prevalence and early detection of metabolic syndrome and cardiovascular disease in seronegative spondyloarthropathy and rheumatoid arthritis patients and their relation to disease activity. Patients and Methods: Our study was carried out on sixty rheumatoid arthritis patients (54 female and 6 males with mean age 46.7 ± 5.5 years) and sixty spondyloarthroapathy patients (27 female and 33 males with mean age 44.9 ± 5.9 years). Results: In RA group, there were 23 patients (38.3%) with metabolic syndrome and 37 patients (61.7%) without metabolic syndrome. In SPA group, there were 21 patients (35%) with metabolic syndrome and 39 patients (65%) without metabolic syndrome. There was no statistical significant difference (p-value > 0.05) between studied groups as regards metabolic syndrome prevalence. There was high statistical significant difference (p-value < 0.001) between patients with MS and patients without MS in RA group regarding age, duration, BMI, FBS, ESR, CRP and DAS28. High statistical significant difference (p-value < 0.001) was detected between patients with MS and patients without MS in SPA group as regards duration, BMI, FBS and BASDI. There was increase in cIMT in RA (0.8 ± 0.2) and SPA groups (0.7 ± 0.1) with high statistical significant difference (p-value < 0.001). Conclusion: MS prevalence increased in patients with RA and SPA, whereas the cardiovascular risks increased in RA patients. The disease activity of both were associated with metabolic syndrome, implicating the role of chronic inflammation in metabolic syndrome development.

Is There a Brain/Heart Interaction in Rheumatoid Arthritis and Seronegative Spondyloartropathies? A Combined Brain/Heart Magnetic Resonance Imaging Reveals the Answer.

To present the interaction between brain/heart and emphasize the role of combined brain/heart magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and other seronegative spondyloarthropathies (SNA). Both traditional cardiovascular disease (CVD) risk factors and intrinsic RA/SNA features contribute to the increased CVD-related morbidity/mortality. CVD in RA usually occurs a decade earlier than age- and sex-matched controls, and RA patients are twice more likely to develop myocardial infarction irrespective of age, history of prior CVD, and traditional CVD risk factors. RA also increases risk of non-ischemic heart failure (HF), valvular disease, and myo-pericarditis. CVD in SNA affects more commonly patients with long-standing disease. Ascending aortitis, aortic/mitral insufficiency, conduction defects, and diastolic dysfunction are the commonest findings in ankylosing spondylitis (AS). CVD is also the leading cause of death in psoriatic arthritis (PsA), due to myopericarditis, diastolic dysfunction, and valvular disease. Brain damage, due to either ischemic or hemorrhagic stroke and silent vascular damage, such as white matter hyperenhancement (WMH), is increased in both RA/SNA and may lead to cognitive dysfunction, depression, and brain atrophy. Magnetic resonance imaging (MRI) is ideal for serial brain/heart evaluation of patients with systemic diseases. RA/SNA patients are at high risk for brain/heart damage at early age, irrespectively of classic risk factors. Until more data will be obtained, a combined brain/heart MRI evaluation can be proposed in RA/SNA with new onset of arrhythmia and/or HF, cognitive dysfunction and/or depression.

Contemporary Primary Total Knee Arthroplasty is Durable in Patients Diagnosed With Ankylosing Spondylitis

IntroductionAnkylosing spondylitis (AS) is a seronegative spondyloarthropathy affecting the axial spine and peripheral joints. Despite innovations in medical management, patients with AS experience two-fold the lifetime risk of total knee arthroplasty (TKA) compared to the general population. Moreover, recent data have indicated a correlation between spinal pathology and outcomes of TKAs. MethodsOur institutional total joint registry identified 19 patients (28 knees) with a diagnosis of AS treated with primary TKA from 2000 to 2016. The mean age at TKA was 68 years, and 84% of patients were men. The mean follow-up period was 6 years. Outcomes included implant survivorship, clinical outcomes, and complications. ResultsSurvivorship free from any revision was 88% at 10 years. A single patient required revision at 8 years for aseptic loosening. Survivorship free from any reoperation was 77% at 10 years. Reoperations included 2 manipulations under anesthesia and 1 superficial wound irrigation and debridement. Mean Knee Society score improved from 46 preoperatively to 89 postoperatively (P < .0001). The mean arc of motion improved from 108o preoperatively to 116° postoperatively (P = .01). There were 6 complications that did not require reoperation. ConclusionPrimary TKAs in patients with AS resulted in significant improvement in clinical outcomes with excellent 10-year implant survivorship. Although 2 manipulations under anesthesia were required, the range of motion was restored postoperatively. These data suggest that the contemporary primary TKA can achieve durable and reliable outcomes in patients with axial skeletal disease resulting from AS. Level of EvidenceIV.

Refractive surgery for the patient with autoimmune diseases.

Autoimmune and immune-mediated diseases are considered contraindications for laser refractive surgeries according to the US Food and Drug Administration's guideline. This guideline, however, is based on limited case reports or complications reported during other intraocular procedures. There have been only a handful of new clinical studies that evaluate the efficacy and safety of refractive surgery in this specific patient population. The aim of this article is to review currently available research and offer updated recommendations for the evaluation and management of laser refractive surgery (LRS) in patients with autoimmune diseases. More recent retrospective studies have reported good refractive outcomes in patients with well controlled autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, among others. No severe sight-threatening complications have been reported in these reports. Although postoperative complications occur, the risk of refractive surgery is comparable with those without autoimmune diseases. With the exception of primary Sjogren's syndrome, patients with autoimmune diseases may be good candidates for LRS if diseases are well controlled and have minimal ophthalmic manifestation. Patients should be made aware of the potential surgical complications and be informed of the currently available data. More multicenter and larger prospective studies are needed to compare the refractive outcomes and surgical complications in patients with and without autoimmune diseases. This will help patients make better informed medical decisions.

SAT-360 Out of Sight, out of Mind: PHEX 3’-UTR C.*231A&amp;gt;G X-Linked Hypophosphatemia in Adults: A Case Study of One Family Pedigree with a Widely Variable Phenotype

Title: Out of Sight, Out of Mind: PHEX 3’-UTR c.*231A>G X-Linked Hypophosphatemia in Adults: A Case Study of One Family Pedigree with a Widely Variable PhenotypeX-linked hypophosphatemia (XLH) is an inherited form of hypophosphatemia that is part of a group of disorders that leads to impaired bone mineralization, which can manifest as rickets in children and osteomalacia in adults. Mutations in PHEX, DMP1, ENPP1, and activating mutations in FGF23 have each been shown as genetic causes for XLH. PHEX is a zinc metallopeptidase which reduces expression of FGF23 through mechanisms that are not fully understood. Inactivating mutations in the PHEX gene cause elevated levels of FGF23, resulting in renal phosphate-wasting, impaired conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and impaired bone mineralization with osteomalacia. Though the clinical significance of FGF23 levels is not clearly understood, it has also been shown that FG23 increases with age.XLH has a reported prevalence of 3.9–5 per 100,000. We speculate that this may be under recognized and that diagnosis may be delayed for many years in those with mild forms of XLH due to non-specific symptoms. Diagnosis may be complicated by normal or low-normal serum phosphorus levels. Adults may be mistakenly diagnosed with ankylosing spondylitis, polyarthritis, osteoarthritis, diffuse idiopathic skeletal hyperostosis and other disorders that cause stiffness. Some clinical manifestations of XLH in adults include dental disease, skeletal and spinal disease, sensorineural hearing loss, kidney stones, renal impairment, and hyperparathyroidism. The PHEX 3’-UTR c.231A>G near the polyadenylation signal has been previously described to cause milder severity in men and seemingly unaffecting women, but data for comparison is limited.We present a large, multigenerational family with a mutation in the PHEX gene (3’-UTR c.*231A>G) demonstrating variable penetrance in the pedigree. Of the members positive for the mutation, the most common symptoms were sensorineural hearing loss, enthesopathy, and dental disease. Most had normal or low-normal phosphorus levels in both genders. Two patients had prior diagnoses of ankylosing spondylitis/ seronegative spondyloarthropathy. In general, males with the mutation had more severe symptoms than females. However, females with a severe phenotype and low phosphorus was also observed. The disease burden was cumulative over time and correlated with serum phosphorus levels. Musculoskeletal symptoms were increased in the members over the age of 60.Sources:Chesher, Douglas et al. Outcome of Adult Patients with X-Linked Hypophosphatemia Caused by PHEX Gene Mutations. Vol. 41. Dordrecht: Springer Netherlands, 2018. Web.Zhang, Cong et al. Clinical and Genetic Analysis in a Large Chinese Cohort of Patients with X-Linked Hypophosphatemia. Vol. 121. Elsevier Inc, 2019. Web.

What do we know about bone morphogenetic proteins and osteochondroprogenitors in inflammatory conditions?

Osteochondroprogenitors are crucial for embryonic bone development and postnatal processes such as bone repair in response to fracture injury, and their dysfunction may contribute to insufficient repair of structural damage in inflammatory arthritides. In the fracture healing, the early inflammatory phase is crucial for normal callus development and new bone formation. This process involves a complex interplay of many molecules and cell types, responsible for recruitment, expansion and differentiation of osteochondroprogenitor populations. In inflammatory arthritides, inflammation induces bone resorption and causes insufficient bone formation, which leads to local and systemic bone loss. While bone loss is a predominant feature in rheumatoid arthritis, inflammation also induces pathologic bone formation at enthesial sites in seronegative spondyloarthropathies. Bone morphogenetic proteins (BMP) are involved in cell proliferation, differentiation and apoptosis, and have fundamental roles in maintenance of postnatal bone homeostasis. They are crucial regulators of the osteochondroprogenitor pool and drive their proliferation, differentiation, and lifespan during bone regeneration. In this review, we summarize the effects of inflammation on osteochondroprogenitor populations during fracture repair and in inflammatory arthritides, with special focus on inflammation-mediated modulation of BMP signaling. We also present data in which we describe a population of murine synovial osteochondroprogenitor cells, which are reduced in arthritis, and characterize their expression of genes involved in regulation of bone homeostasis, emphasizing the up-regulation of BMP pathways in early progenitor subset. Based on the presented data, it may be concluded that during an inflammatory response, innate immune cells induce osteochondroprogenitors by providing signals for their recruitment, by producing BMPs and other osteogenic factors for paracrine effects, and by secreting inflammatory cytokines that may positively regulate osteogenic pathways. On the other hand, inflammatory cells may secrete cytokines that interfere with osteogenic pathways, proapoptotic factors that reduce the pool of osteochondroprogenitor cells, as well as BMP and Wnt antagonists. The net effect is strongly context-dependent and influenced by the local milieu of cells, cytokines, and growth factors. Further elucidation of the interplay between inflammatory signals and BMP-mediated bone formation may provide valuable tools for therapeutic targeting.

Reactive Arthritis The Reiter-Fiessinger-Leroy Syndrome

The role of creating the expression of reactive arthritis rests with AHO in 1973, which defines reactive arthritis as an acute, unsupportive, sterile inflammatory arthropathy, arising from infections located at a distance in people with a certain genetic predisposition; the disease is systemic and, despite its name, is not limited to the joints. Reactive arthritis (RA), included in Reiter syndrome (with the classic triad of urethritis, conjunctivitis and arthritis), is a non-suppurative inflammatory joint pathology, with a minimal autoimmune component, which it is installed following intestinal or urogenital infections, mainly in people with genetic predisposition. Reactive arthritis is a form of arthritis that affects the joints, urethra, eyes and membranes and sometimes the skin and mucous membranes. This condition is also called Reiter`s syndrome, although this name only indicates a subtype. Reactive arthritis is a seronegative spondyloarthropathy, which brings together a group of disorders that cause inflammation in the body, especially in the spine - such as ankylosing spondylitis, and in the legs. The study covers a number of 20 patients (11 men, 9 women) admitted to the Rheumatology Service of the Clinical Recovery Hospital, between 2010 and 2011, aged over 20, who were diagnosed with reactive arthritis. The existence of a structural similarity between the etiological agent and the HLA-B27 molecule determines either the recognition of the disease-causing germ as a self, so that no immune response will be initiated against it and the antigen will be able to trigger the disease, or the recognition of the germ as nonself, with the triggering of an immune response aimed at both itself and against the HLA-B27 molecule carrying cells of similar structure. Reactive arthritis (RA), included in the Reiter syndrome (with the classic triad of urethritis, conjunctivitis and arthritis), is a non-suppurative inflammatory joint pathology, with a minimal autoimmune component, which is installed as a result of intestinal or urogenital infections, mainly in people with genetic predisposition.

Imaging of diffuse idiopathic skeletal hyperostosis (DISH)

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment,...

Association Study between Psoriatic Arthritis and Killer Immunoglobulin-Like Receptor (KIR) Genes: A Meta-Analysis

ABSTRACT Background: Psoriatic Arthritis (PsA) is a seronegative spondyloarthropathy frequently associated with psoriasis. Studies have shown different members of the KIR (Killer Immunoglobulin-like Receptor) gene family may act as potential susceptibility factors; however, data have been inconsistent or with a reduced sample size. Therefore, the objective of this investigation was to determine associations between KIR genes and PsA susceptibility a meta-analysis approach. Methods: We performed a systemic search on PubMed, Scopus, and Web of Science to identify association studies linking KIR genes with PsA susceptibility. The search cut-off was May 2019. Odds Ratio (OR), 95% Confidence Intervals (95% CI), and forest plots were obtained for each KIR gene. Publication bias was evaluated by Begg and Egger linear regression tests. Results: Five articles were included in this meta-analysis. The KIR2DL2, 2DS1, 2DS2, and 2DS3 genes were positively associated with susceptibility to PsA (OR = 1.269, p = .003; OR = 1.392, p < .001; OR = 1.279, p = .002; and OR = 1.230, p = .038, respectively). In Caucasians, positive association with susceptibility to PsA were maintained by KIR2DL2, 2DS1, and 2DS2 genes (OR = 1.257, p = .005; OR = 1.535, p = .003; and OR = 1.267, p = .004, respectively). Conclusion: These associations suggest that KIR2DL2, 2DS1, 2DS2, and 2DS3 genes are susceptibility factors for PsA.

Interleukin-23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy.

The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL-23R or the interleukin-23 (IL-23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin-17 (IL-17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL-23R-expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL-23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL-23R-expressing myeloid cells and various innate and adaptive T cells that produce IL-17 family cytokines have also been described in the human enthesis. Blockade of IL-23 pathway with either anti-p40 or anti-p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL-23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

Surgical Stabilization of a Cervical Fracture in a Patient with Ankylosing Spondylitis in the Sitting Position

Ankylosing spondylitis is a seronegative spondyloarthropathy promoting alteration of the integrity and biomechanics of the spine. This leads to a brittle and hyperkyphotic spine with an increased risk of cervical spine fracture. Cervical spine fractures in people with ankylosing spondylitis are often unstable three-column extension injuries that are managed with posterior long segment fusions. Kyphotic deformity, body habitus, and increased airway pressures complicate these procedures. A 65-year-old man presented with neck pain following a fall from a roof. He was found to have a displaced transverse three-column fracture of C6/7. The original plan was to perform a staged circumferential cervical fusion with anterior cervical fusion first to make prone positioning for posterior fusion safer. CT after anterior cervical fusion from C5 to C7 demonstrated improved alignment of the fractured posterior elements. Due to concern of increased peak airway pressures and awkward positioning, planned prone positioning for posterior approach was abandoned. A posterior long segment fusion from C4 to T3 was performed in the seated position. CT demonstrated the hardware was appropriately placed. The patient’s hospital course was uncomplicated, and he was followed up with cervical spine x-rays. Two years later, he denied neck pain or functional impairment and x-ray demonstrated healing of the fracture. Utilizing the sitting position for the posterior cervicothoracic fusion portion of a combined anterior-posterior approach can overcome complication-spurring positioning difficulties and provide proper surgical management of an unstable cervical spine fracture in a patient with ankylosing spondylitis.

High accuracy of HLA-B*27 genotyping by allele-specific real-time polymerase chain reaction in a heterogeneous population compared to flow cytometry and single nucleotide polymorphism detection assays

HLA-B27 is a risk marker for ankylosing spondylitis and other associated seronegative spondyloarthropathies. We compared three methods of HLA-B*27 typing in a New South Wales (NSW) population: flow cytometry, rs4349859 single nucleotide polymorphism (SNP) detection assay, and allele-specific real-time polymerase chain reaction (RT-PCR) analysis of exons 2 and 3. Over a 5-month period, 543 samples underwent flow cytometric testing and RT-PCR high-resolution melt analysis of rs4349859 SNP and of exon 2 (5' fragment) and exon 3. In the third method, positive samples were further analysed with fluorescent resonance emission transfer (FRET) RT-PCR of exon 2 fragments, 2a and 2b. HLA-B*27 and other genotypes were confirmed by Sanger sequencing of a 600 base pair fragment of exons 2 and 3. In our cohort, the rs4349859 SNP method had 78.6% sensitivity and 98.7% specificity. Screening with exon 2 (5' fragment) and exon 3 RT-PCR provided 100% sensitivity. Further testing with exon 2a and 2b FRET RT-PCR produced 100% specificity. This cascade approach with allele-specific RT-PCR assays was able to differentiate all samples into HLA-B*27 subtypes. HLA-B*27 genotyping with allele-specific RT-PCR assays, to screen for and confirm HLA-B27 positive samples, was more sensitive and specific than flow cytometry and rs4349859 SNP assays. It is a potentially cost-effective method for differentiating HLA-B27 subtypes. Our cascade genetic testing approach is suitable for replacing the current flow cytometric HLA-B27 assay for the heterogeneous NSW population.

Association between secretor status and Lewis phenotype with seronegative spondyloarthritis as indicator of autoimmunity

The classical paradigm of autoimmune pathogenesis involving specific genetic makeup and exposure to environmental triggers has been challenged recently by the addition of a third element, the loss of intestinal barrier function. Regardless of HLA B27 phenotype or gastrointestinal symptoms, evidence of ileitis, ileocolitis or colitis exists in patients with spondyloarthropathy. The FUT2 secretory gene is a strong candidate for Crohn's susceptibility by shaping the functional states of mucosal microbiota and may thus have influence on the release of zonulin, the main regulator of gut permeability. Gram negative bacteria precipitate and may be involved in the pathogenesis of spondyloarthropathies. Susceptibility to many infectious agents is associated with ABO blood group or secretor state. Patients who cannot secrete ABO and Lewis blood group antigens into body fluids, an ability controlled by a single gene on chromosome 19, are known to be at increased risk of certain autoimmune diseases associated with human leukocyte antigen (HLA) markers. Lewis (Le) blood group phenotype can be used to infer secretor status. The objective of this study was to determine the distribution of secretor state and Lewis blood group phenotype in patients with seronegative spondyloarthropathies and healthy control subjects. Hundred and ten (110) patients with seronegative spondyloarthropathies (58 females and 52 males) and 103 control (74 males and 29 females) subjects participated in this study. Samples of saliva and blood were subjected to haemagglutination inhibition tests for determination of secretor status and Lewis phenotype. A total of 92(84%) patients and 92 (89%) control subjects were secretors while 18 (16%) patients and 11 (11%) control subjects were non-secretors. There was no statistically significant difference (?2 1,461 p&lt;0,05 and degrees of freedom 1) in distribution of secretor status in comparison to seronegative spondyloarthropathies by comparing two observed populations. Seven patients had modified (reduced) expression of Lewis b antigen on their erythrocytes. Reduction of Lewis b antigen expression was not observed on erythrocytes of healthy subjects. Reduced expression of Lewis b antigen could be a consequence of the inflammatory process within the gut and it also suggests several pathogenic mechanisms which may be relevant to the synthesis of Lewis antigens inside the gut or its absorption on erythrocytes in patients with spondyloarthropathy.

Interleukin-18, interleukin-20, and matrix metalloproteinases (MMP-1, MMP-3) as markers of psoriatic arthritis disease severity and their correlations with biomarkers of inflammation and turnover of joint cartilage.

IntroductionPsoriatic arthritis (PsA) is a chronic, seronegative spondyloarthropathy characterised by joint inflammation and psoriatic skin changes. Recent data indicate that interleukin-18 (IL-18) and interleukin-20 (IL-20) may be involved in the aetiopathogenesis of PsA.AimTo evaluate the potential role of IL-18, IL-20, and matrix metalloproteinases (MMP-1, MMP-3) in the pathogenesis of PsA and their correlations with other markers of inflammation and destruction of joint cartilage, as well as clinical changes.Material and methodsThe study included 24 patients with PsA and 26 healthy volunteers as a control group. The concentration of IL-18 and IL-20, c-reactive protein (CRP), metalloproteinase-1 and -3 (MMP-1, MMP-3), cartilage oligomeric matrix protein (COMP), aggrecan (PG-AG), and human cartilage glycoprotein (YKL-40) in serum was determined. Clinical severity of the disease according to the BSA, PASI, and DLQI as well as tender and swollen joint count (TJC, SJC) were also evaluated.ResultsThe concentration of IL-18 was statistically significantly higher in the serum of patients with PsA than in the control group (62.87 pg/ml vs. 16.73 pg/ml, p < 0.0049). Serum IL-20 levels in PsA patients were also higher than in the control group, but without statistical significance (p = 0.2939). The ROC curves showed: AUC = 0.81 for IL-18, AUC = 0.75 for IL-20, AUC = 0.96 for COMP, and AUC = 0.89 for MMP-3.ConclusionsIL-18 and IL-20 as well as MMP-3 and COMP may be sensitive markers in the diagnosis of PsA.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Evaluation of ERAP1 gene single nucleotide polymorphisms in immunomodulation of pro-inflammatory and anti-inflammatory cytokines profile in ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a prototype of chronic inflammatory arthritis termed seronegative spondyloarthropathies that typically affects the joints. Among the non-Human leukocyte antigen (HLA) loci, the strongest association has been observed with Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene single nucleotide polymorphisms (SNPs). Moreover, the effect of ERAP1 gene SNPs on the pro-inflammatory and anti-inflammatory cytokines in AS disease has still been poorly elucidated. In this study, we aimed to determine the association of ERAP1 gene SNPs (rs30187 and rs2287987) with AS risk as well as their effect on the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, with emphasis on the immunoregulation of the IL-17/IL-23 pathway, in an Iranian population. MethodsWe performed Single specific primer (SSP)-PCR for genotyping of 160 AS patients and 160 healthy controls. After isolation of peripheral blood mononuclear cells (PBMCs), total RNA of PBMCs was isolated, complementary DNA (cDNA) was synthesized, and quantitative analyses of mRNA expression of cytokines were performed by Real-time PCR for 40 HLA-B27 positive AS patients and 40 healthy individuals as controls. ResultsIt was seen that T allele of rs30187 (OR = 1.54, 95% CI = 1.07–2.22, P = 0.017) and C allele of rs2287987 (OR 1.50, 95% CI 1.05–2.14, P = 0.024) were associated with the risk of AS. Both of these alleles were associated more strongly in the HLA-B27 positive AS patients. There was a significant overexpression of mRNAs of pro-inflammatory (IL-17A, IL-17F, IL-23, TNF-α and IFN-γ), while downregulation of anti-inflammatory cytokines (IL-10 and TGF-β) in PBMCs from 40 HLA-B27 positive AS patients in comparison to controls. AS patients with rs30187 SNP TT genotype expressed mRNA of IL-17A, IL-17F, and IL-23 significantly higher than patents with CT and CC genotypes for this SNP. ConclusionsThis study represented the association of ERAP1 gene rs30187 and rs2287987 polymorphism with the risk of AS. Additionally, it appears that rs30187 polymorphism may be involved in the immunomodulation of the IL-17/IL-23 pathway in the AS disease.

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

In-clinic experience with half dose Etanercept Biosimilar in Indian patients with rheumatic diseases: A single center observational study

Synovial inflammation in rheumatic diseases leads to cartilage damage, bone erosions and subsequent joint destruction causing significant morbidity. Seronegative spondyloarthropathy or seropositive rheumatoid arthritis and their variants once diagnosed should be treated early to prevent the bony erosion. Delay of up to nine months in initiating Disease-Modifying Anti-rheumatic Drug (DMARD) definitely impacts clinical outcome several years later. During the last decade, introduction of biologics like TNF inhibitors have revolutionized the management of rheumatic diseases leading to early and prompt control over disease activity. One of the TNF inhibitors, Etanercept over the time has proven itself to be a reliable option for treatment of rheumatoid arthritis, spondyloarthropathy, psoriatic arthritis and other rheumatic diseases. Major drawback with biologics like Etanercept is their cost. Indian population differs substantially from western population in terms of height, weight, phenotype as well as genotype. Due to this difference in demographic profile and cost-affordability, many drugs have been used in low dose in Indian population. Etanercept can be a safe and effective option in rheumatic diseases even at half its recommended dose in countries like India where the average weight of people is less as compared to western population. Low dose also improves affordability, reduces risk of infections and may be, minimizes need for vaccination. In the modern era of biologicals, biosimilars have a huge potential to treat rheumatic diseases in India where affordability is a real challenge. This study was over 256 patients. Keywords: Spondyloarthropathy, DMARD, TNF inhibitor, Biologicals, Biosimilars.

Association Between Human Leukocyte Antigen-B*27 and Pathogenesis in Seronegative Spondyloarthropathies in Federation of Bosnia and Herzegovina.

This study aims to investigate the low-resolution human leukocyte antigen (HLA)-B locus polymorphisms between unrelated healthy individuals and patients with diagnosis of seronegative spondyloarthropathies and determine risky and protective allelic groups and genotypes. The study included 104 healthy control individuals (52 males, 52 females; median age 43 years; range 2 to 76 years) and 96 patients (43 males, 53 females; median age 28.5 years; range 2 to 67 years) diagnosed with: ankylosing spondylitis (AS) (n=19), reactive arthritis (n=19), psoriatic arthritis (n=28) and undifferentiated spondyloarthropathies (n=30). Genomic deoxyribonucleic acid was extracted from peripheral blood to detect allelic groups of HLA class I and II. Single-specific-primer polymerase chain reaction was used for HLA genotyping and visualization of products after their separation on 1.5% agarose gel for horizontal gel electrophoresis. Significantly increased frequency was found for HLA-A*02 and HLA-B*27 allelic variants in all groups of patients. The increased frequency of the HLA-B*35 allelic group in the control group represents the protective gene variant for the occurrence of AS. The predisposing genotype (HLA-B*27/B*44 and B*27/B*51) for the onset of disease was only found in AS patients. This study shows the strong association of HLA-B*27 antigen with spondyloarthropathies, which is considered a risk variant of the gene for the onset of disease. Protective and risky allelic variants and genotypes are rare and their detection as well as increased frequency are possible if larger numbers of patients are involved.

Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders.

Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-α inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-α antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet’s syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients.