Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study.

Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 × 10-5) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.

Using Ultrasound to Improve Diagnostic Confidence and Management of Psoriatic Disease: Highlights From the GRAPPA 2023 Ultrasound Workshop.

The sensitivity of ultrasound (US) to detect, characterize, and monitor the relevant pathologies of psoriatic arthritis (PsA), including synovitis, enthesitis, tenosynovitis, and dactylitis, has made it an attractive tool for informing clinical decisions. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US working group ran 2 sessions during the annual GRAPPA meeting held in July 2023 in Dublin, Ireland. During the first workshop, the group presented 2 topics, followed by a live demonstration and a group discussion. The 2 topics were (1) an overview of the Diagnostic Ultrasound Enthesitis Tool (DUET) enthesitis scoring methodology, and (2) small hand-held probes-will the promise deliver? The live demonstration that followed compared the performance of 2 hand-held US (HHUS) devices vs a console US machine in patients with PsA, and the interactive group discussion considered gaps in the literature and future research suggestions relating to HHUS and its application in psoriatic disease. During the second session, the US working group provided further updates regarding the GRAPPA US studies currently underway or recently completed.

GRAPPA 2023: Major Projects, Key Advances, and Milestones.

At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations.

The Role of Ultrasound in Research and Clinical Practice in Psoriatic Arthritis: Highlights From the GRAPPA Ultrasound Workshop.

Ultrasound (US) is a valuable imaging modality that can accurately identify relevant features of psoriatic arthritis (PsA), such as synovitis, tenosynovitis, and enthesitis. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Ultrasound Committee ran a workshop during the annual GRAPPA meeting that was held in July 2020. The group presented the following 3 topics: (1) the transition from psoriasis to PsA and the role of US; (2) the effect of biomechanical forces on the entheses in health and disease, and insight for PsA pathogenesis; and (3) differentiation of enthesitis from pain sensitization: use and limitations of clinical and sonographic evaluation of enthesitis. This article summarizes the key messages from this workshop.

The impact of smoking on prevalence of psoriasis and psoriatic arthritis.

OBJECTIVES: In this systematic literature review and meta-analysis, we aimed to investigate the impact of cigarette smoking on the prevalence and incidence of psoriasis and psoriatic arthritis (PsA). METHOD: We performed a systematic literature review using the MEDLINE, EMBASE and Cochrane Central Register databases. The literature included publications from January 1980 to July 2019. The studies that provided clear information on the number of patients with ever smoking data were included in the meta-analysis. RESULTS: The systematic literature review identified 52 and 24 articles for the prevalence of smoking in psoriasis and PsA, respectively. Of these, 16 articles on psoriasis and three and four (general population and psoriasis, respectively) articles on PsA met the criteria and were included in the meta-analysis. The prevalence of ever smoking was increased in psoriasis compared with the general population (OR: 1.84; 95% CI: 1.4, 2.3). For PsA the prevalence of ever smoking was reduced in psoriasis patients (OR: 0.70; 95% CI: 0.60, 0.81), but not changed compared with the general population (OR: 1.10; 95% CI: 0.92, 1.32). CONCLUSION: This meta-analysis showed that ever smoking increases the risk of psoriasis in the general population, but may reduce the risk of PsA in psoriasis patients. The latter may be also due to the collider effect. Whether smoking cessation neutralizes the risk of developing psoriasis requires a well-defined smoking data collection for the past history and this is currently unavailable in the literature.

Evidence that systemic therapies for psoriasis may reduce psoriatic arthritis occurrence.

OBJECTIVES: Contemporary biologic therapies for psoriasis are independently licensed for psoriatic arthritis (PsA). Since skin disease generally predates PsA and PsA has a subclinical phase, we investigated the pattern of PsA evolution in psoriasis treated with biologic agents compared to other medications including oral therapy, topical agents or no treatments. METHODS: A retrospective chart review was performed in psoriasis patients with musculoskeletal symptoms referred for rheumatological assessment. Patients who had a final diagnosis of PsA were identified. The frequency and clinical features of PsA were compared for biologics versus the other strategies. RESULTS: Between 2015-18, 203 psoriasis patients were referred for musculoskeletal symptoms with 25 on biologics, 31 on non-biologic systemic therapies and 147 on topical/no therapies. A final diagnosis of PsA was similar in all groups (biologics: 36%; non-biologic systemic treatments: 35.4%; none/local treatments: 37.4%). Most patients had musculoskeletal symptoms before systemic therapy initiation but new onset PsA was evident in 12% (3/25) biologics treated patients, 9.6% (3/31) in non-biologic systemic therapy patients and was significantly higher in patients on topical/no therapy (55/147; 37.4%, p<0.001). Among patients with PsA, none of the patients on biologics exhibited dactylitis compared to 28.6% of other systemic treatments and 48.6% of none/local treatments (p=0.046). CONCLUSIONS: New symptoms and signs leading to PsA diagnosis appear to decrease with systemic treatments. The characteristic PsA dactylitis lesion was not evident in the biologic therapy group.

The Ottawa Panel guidelines on programmes involving therapeutic exercise for the management of hand osteoarthritis.

OBJECTIVE:: To identify programmes involving therapeutic exercise that are effective for the management of hand osteoarthritis and to provide stakeholders with updated, moderate to high-quality recommendations supporting exercises for hand osteoarthritis. METHODS:: A systematic search and adapted selection criteria included comparable trials with exercise programmes for managing hand osteoarthritis. Based on the evaluated evidence, a panel of experts reached consensus through a Delphi approach endorsing the recommendations. A hierarchical alphabetical grading system (A, B, C+, C, C-, D-, D, D+, E, F) was based on clinical importance (≥15%) and statistical significance ( P < 0.05). RESULTS:: Ten moderate- to high-quality studies were included. Eight studies with programmes involving therapeutic exercise (e.g. range of motion (ROM) + isotonic + isometric + functional exercise) seemed to be effective. Forty-six positive grade recommendations (i.e. A, B, C+) were obtained during short-term (<12 weeks) trials for pain, stiffness, physical function, grip strength, pinch strength, range of motion, global assessment, pressure pain threshold, fatigue and abductor pollicis longus moment and during long-term (>12 weeks) trials for physical function and pinch strength. CONCLUSION:: Despite that many programmes involving exercise with positive recommendations for clinical outcomes are available to healthcare professionals and hand osteoarthritis patients that aid in the management of hand osteoarthritis, there is a need for further research to isolate the specific effect of exercise components.

The knitting community-based trial for older women with osteoarthritis of the hands: design and rationale of a randomized controlled trial.

BACKGROUND: The prevalence of hand osteoarthritis (HOA) has been reported to be higher amongst women over 50 years old (66%) compared to men of the same age (34%). Although exercise therapy has been shown effective in reducing symptoms and disability associated with HOA, adherence to treatment programs remains low. The primary objective of this RCT is to examine the effectiveness of a 12-week knitting program for morning stiffness (primary outcome) and pain relief (secondary outcome) 2 h post-wakening in females (aged 50 to 85 years old) with mild to moderate hand osteoarthritis (HOA). METHODS/DESIGN: A single-blind, two-arm randomized controlled trial (RCT) with a parallel group design will be used to reach this objective and compare results to a control group receiving an educational pamphlet on osteoarththritis (OA) designed by the Arthritis Society. The premise behind the knitting program is to use a meaningful occupation as the main component of an exercise program. The knitting program will include two components: 1) bi-weekly 20-min knitting sessions at a senior's club and 2) 20-min home daily knitting sessions for the five remaining weekdays. Participants assigned to the control group will be encouraged to read the educational pamphlet and continue with usual routine. Pain, morning stiffness, hand function, self-efficacy and quality of life will be measured at baseline, six weeks, 12 weeks (end of program) with standardized tools. We hypothesize that participants in the knitting program will have significant improvements in all clinical outcomes compared to the control group. A published case study as well as the preliminary results of a feasibility study as examined through a 6-week pre-post study (n = 5 women with HOA) involving 20-min daily knitting morning sessions led to this proposed randomized controlled trial research protocol. This article describes the intervention, the empirical evidence to support it. DISCUSSION: This knitting RCT has the potential to enhance our understanding of the daily HOA symptoms control and exercise adherence, refine functional exercise recommendations in this prevalent disease, and reduce the burden of disability in older women. TRIAL REGISTRATION: (ACTRN12617000843358) registered on 7/06/2017.

Options for Assessing Joints and Entheses in Psoriatic Arthritis by Ultrasonography and Magnetic Resonance Imaging: How to Move Forward.

Psoriatic arthritis (PsA) is a heterogeneous disease with various manifestations of musculoskeletal inflammation. Recent advances in imaging, including ultrasound (US) and magnetic resonance imaging (MRI), allow for the accurate evaluation of the extent of inflammation and damage in the peripheral joints, spine, and entheses. The development and validation of outcome measures are critical steps in creating standardized evaluations of musculoskeletal inflammation and damage in psoriatic patients. At the 2017 meeting of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA), recent work on outcome measures from the GRAPPA US and MRI working groups was summarized. The GRAPPA US group has been developing and validating a sonographic enthesitis scoring system in PsA. The GRAPPA MRI group focuses on the evaluation of whole-body MRI for the assessment of musculoskeletal inflammation in the joints and entheses in patients with PsA.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r(2) < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10(-9); and rs189754752, OR = 2.47, p = 4.22 × 10(-9)). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10(-12)). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10(-8)).

Outcome measures for Takayasu's arteritis.

PURPOSE OF REVIEW: Takayasu's arteritis (TAK) is a large-vessel vasculitis with a chronic, indolent course affecting the aorta and its main branches. This review will describe the recent studies to develop validated outcome measures to assess TAK. RECENT FINDINGS: TAK is traditionally assessed with a physician's global assessment including symptoms and signs of inflammation and vascular insufficiency, acute-phase reactants (APRs), and imaging including conventional digital subtraction angiography, computerized tomographic, and magnetic resonance angiography, and recently 18-FDG-PET. Recent attempts to develop a validated tool for disease assessment include the Indian Takayasu Clinical Activity Score (ITAS2010), which incorporates clinical signs and symptoms with APRs in a simplified and weighted adoption of the Birmingham Vasculitis Activity Score. Among biomarkers to assess clinical activity, pentraxin-3 is perhaps the most promising, but its validity and superiority against APRs in clinical practice need to be demonstrated. Patient-reported outcomes (PROs) are increasingly recognized as of substantial importance to measure in clinical trials; in addition to so-called 'generic' tools such as the SF-36 or measures of fatigue, disease-specific instruments would likely help capture aspects of TAK not measured by generic quality-of-life assessments or physician-based tools. SUMMARY: Although outcome measures for TAK are not sufficiently validated, progress in the assessment of TAK is reflected in recent studies with new tools such as ITAS2010, new biomarkers, and a variety of PROs.

Magnetic resonance imaging assessment of axial psoriatic arthritis: extent of disease relates to HLA-B27.

OBJECTIVE: To determine the prevalence, on magnetic resonance imaging (MRI), of bone marrow edema lesions in symptomatic axial psoriatic arthritis (PsA), and to compare this prevalence with that in nonradiographic axial spondyloarthritis (SpA) and ankylosing spondylitis (AS) and its relationship to HLA-B27 status. METHODS: We performed a cross-sectional audit of MRI scans of lumbar spine (L-spine) and sacroiliac (SI) joints. Using the semiquantitative Leeds Scoring System in which bone marrow edema is graded from 0 to 3 according to severity of the lesions, MRI scans were scored independently by 2 expert readers who were blinded to the clinical characteristics of the patients. Concordant data from the 2 readers were used to report on definite lesions. RESULTS: MRIs from 76 patients with comparable age ranges were categorized into 3 groups: those from PsA patients, those from patients with nonradiographic axial SpA, and those from AS patients. HLA-B27 positivity was similar in PsA patients (10 of 33) and patients with nonradiographic axial SpA (10 of 24) and higher in AS patients (18 of 19). Total MRI scores (L-spine plus SI joints) were higher in AS patients than in PsA patients (P = 0.025) or in patients with nonradiographic axial SpA (P = 0.007). A relationship was seen between the severity and extent of disease and HLA-B27 positivity in PsA patients, which was comparable to that in AS patients. HLA-B27-negative PsA patients had lower MRI scores than HLA-B27-positive PsA patients (P = 0.03) and AS patients (P = 0.006), whereas scores were similar in HLA-B27-positive PsA patients and AS patients. Similarly, MRI scores of HLA-B27-negative patients with nonradiographic axial SpA were lower than those of AS patients (P = 0.01). CONCLUSION: HLA-B27 positivity defines a group of patients with more severe axial bone marrow edema that is likely related to the classic AS phenotype. Clinically, HLA-B27-negative PsA is more likely to be reported as a "negative" MRI examination result.

The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development.

OBJECTIVE: Subclinical enthesopathy is recognised in both psoriasis and psoriatic arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test the hypothesis that subclinical enthesopathy in PsA was associated with an 'inflammatory' or vascular phenotype compared to that seen in psoriasis. METHODS: 100 patients with a mean age of 46.3 years (SD 15) (42 with psoriasis and 58 with PsA) and 23 matched healthy controls (HC) from two centres were included. 1230 lower limb entheses were scanned by ultrasonographers blinded to clinical details. Both inflammatory and chronic features of enthesopathy were scored. RESULTS: Psoriasis patients (with or without arthritis) were more likely to express a vascular phenotype, with higher inflammation-related enthesopathy scores than HC (for inflammation p<0.0001, for chronicity p=0.02, for total ultrasound scores p<0.0001). The PsA patients had higher ultrasound enthesopathy scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC (inflammation p<0.0001, chronicity p=0.003). When symptomatic entheses were excluded, PsA patients still had higher PD scores than psoriasis patients (p=0.003). Doppler positivity in at least one entheseal site was observed more frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002). CONCLUSIONS: This study shows that the ultrasound appearances of subclinical enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA patients having more PD. This is suggestive of a more inflammatory or vascular process in PsA, and offers potentially novel insights into the progression from skin to joint disease in psoriasis.

Potential use of optical coherence tomography and high-frequency ultrasound for the assessment of nail disease in psoriasis and psoriatic arthritis.

BACKGROUND/OBJECTIVE: Psoriatic nail disease is increasingly recognised to be of major clinical and research relevance. Clinical assessment remains the current gold standard for its evaluation. OBJECTIVE: We compared optical coherence tomography (OCT) and ultrasound (US) for nail disease assessment in psoriatic disease. METHODS: 18 patients with at least one involved nail and 12 healthy controls were scanned using OCT; psoriatic patients also had an US scan (using a linear probe at 9-14 MHz). Nail and contour abnormalities were documented. Clinical onychopathy was scored independently using the modified Nail Psoriasis Severity Index. RESULTS: Among 180 nails, 67.8% had clinical findings whereas 33.9% were abnormal by US and 44.4% had abnormalities on OCT. A positive OCT had a sensitivity and specificity of 44.4 and 95.8%, respectively, with a positive likelihood ratio of 10.7 for nail disease. OCT demonstrated 76.3% absolute agreement compared with clinical assessment and 65% with US. OCT detected subtle abnormalities in 12 clinically normal nails and in 41 nails with normal US findings. CONCLUSION: These findings show that OCT has a potential for the systematic characterisation of psoriatic nail changes and could be useful in diagnosis and more objective assessment of treatment response.

Developing Ultrasound Measures for the Early Diagnosis of Psoriatic Arthritis.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound (US) steering committee provided an update at GRAPPA's 2022 annual meeting on activities to enable earlier diagnosis of psoriatic arthritis. An update of the Diagnostic Ultrasound Enthesitis Tool (DUET) study included preliminary reliability results for US enthesitis elementary lesions. Common scanning pitfalls were reviewed. New projects included widening the scope of US beyond large entheses and validating small point-of-care US probes to evaluate enthesitis.

Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension.

BACKGROUND: Evaluate the impact of sex on tofacitinib efficacy, safety and persistence (time to discontinuation) in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from two phase 3 randomised controlled trials. Patients were randomised to tofacitinib 5 mg or 10 mg two times per day, adalimumab 40 mg every 2 weeks or placebo. Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20/50/70, minimal disease activity (MDA), Psoriasis Area Severity Index (PASI)75, change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI) and ∆Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was assessed to month 12 and persistence was assessed to month 42 of a long-term extension study. RESULTS: Overall, 816 patients were included (54.3% females). At baseline, higher tender joint counts, enthesitis scores and worse HAQ-DI and FACIT-F were reported in females versus males; presence of dactylitis and PASI were greater in males versus females. At month 3, tofacitinib efficacy generally exceeded placebo in both sexes. Overall, similar ACR20/50/70, PASI75, ∆HAQ-DI and ∆FACIT-F were observed for tofacitinib between sexes; females were less likely to achieve MDA. Similar proportions of males/females receiving tofacitinib (both doses) experienced treatment-emergent adverse events (AEs). Serious AEs occurred in 3.4%/6.6% and 4.0%/5.9% males/females with tofacitinib 5 mg and 10 mg two times per day. Persistence was generally similar between sexes. CONCLUSION: Tofacitinib efficacy exceeded placebo in both sexes and was comparable between sexes. Consistent with previous studies of PsA treatments, females were less likely to achieve MDA, likely due to baseline differences. Safety and time to discontinuation were generally similar between sexes. TRIAL REGISTRATION NUMBER: NCT01877668; NCT01882439; NCT01976364.

Validation of the ASAS criteria and definition of a positive MRI of the sacroiliac joint in an inception cohort of axial spondyloarthritis followed up for 8 years.

BACKGROUND: The new Assessment of SpondyloArthritis international Society (ASAS) criteria classify axial spondyloarthritis (SpA) into human leucocyte antigen-B27 and/or imaging-based arms. To aid implementation, ASAS has proposed a definition of a positive MRI for active sacroiliitis. OBJECTIVE: The authors aimed to test the diagnostic and predictive value of the ASAS criteria and definition of a 'positive' MRI. METHODS: Baseline MRI scans on 29 patients with early inflammatory back pain and 18 controls were read independently by four experienced rheumatologists. Both arms of the criteria were tested against a 'gold standard' of physician diagnosis of SpA. MRI abnormalities were assessed according to a global assessment of MRI and the ASAS definition. Sensitivity, specificity and likelihood ratios for individual and concordant reader data were calculated for axial SpA diagnosis at baseline and the development of radiographic sacroiliitis, fulfilling the modified New York criteria at 8 years. RESULTS: All patients were classified as having axial SpA, with more patients fulfilling the imaging arm (83%, n=24/29) than the human leucocyte antigen B27 arm (62%, n=18/29). Concordant reader data showed that the baseline MRI had high diagnostic utility for SpA according to global assessment (sensitivity/specificity: 66%/94%, LR+ (positive likelihood ratio) 11.8, LR- (negative likelihood ratio) 0.4) and ASAS definition (sensitivity/specificity: 79%/89%, LR+ 7.1, LR- 0.2). Likewise, a positive baseline MRI had 100% sensitivity for subsequent radiographic sacroiliitis by either assessment, although specificity was lower (56% for global assessment and 33% for ASAS definition). CONCLUSION: Both arms of the ASAS criteria have good diagnostic utility in early SpA, although they are of limited value for the prediction of radiographic progression. This may be due to the definition of a positive MRI for sacroiliitis that lacks specificity at baseline.

Psoriasis patients with nail disease have a greater magnitude of underlying systemic subclinical enthesopathy than those with normal nails.

OBJECTIVE: Enthesopathy is a major feature of psoriatic arthritis (PsA), which is supported by imaging studies. Given that nail disease often predates PsA and that the nail is directly anchored to entheses, the authors asked whether nail involvement in psoriasis equates with a systemic enthesopathy. METHODS: Forty-six patients with psoriasis (31 with nail disease) and 21 matched healthy controls (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an ultrasonographer blinded to clinical details. RESULTS: Psoriasis patients had higher enthesitis scores than HC (median (range) 21 (0-65) vs 11 (3-39), p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0-65)) than in patients without nail disease (15 (5-26), p=0.02) and HC (11 (3-39), p=0.003). Inflammation scores of patients with nail disease (13 (0-34)) were higher than patients without nail disease (8 (2-15), p=0.02) and HC (5 (0-19), p<0.001). Modified nail psoriasis severity index scores were correlated to both inflammation (r(2)=0.45, p=0.005) and chronicity scores (r(2)=0.35, p=0.04). No link between the psoriasis area and severity index and enthesitis was evident. CONCLUSION: The link between nail disease and contemporaneous subclinical enthesopathy offers a novel anatomical basis for the predictive value of nail psoriasis for PsA evolution.

PDCD1 polymorphisms are not associated with Takayasu's arteritis in Turkey.

OBJECTIVES: Takayasu's arteritis (TA) is a chronic arterial inflammation of unknown etiology involving mainly the aorta and its major branches. Based on the associations of programmed death-1 (PD-1) protein encoding gene (PDCD1) with connective tissue diseases and vasculitides, PDCD1 polymorphisms are studied for susceptibility to TA in this study. METHODS: The study group is made up of TA patients (n=229) fulfilling the 1990 ACR classification criteria and compared to 193 healthy controls (HC). PD-1.3, PD-1.5 and PD-1.6 single nucleotide polymorphisms of PDCD1 gene are genotyped by polymerase chain reaction and restriction analysis (PCR-RFLP). RESULTS: The distribution of PD-1.5 polymorphism in TA patients and HC revealed a similar presence of TT genotype in patients and controls (13.3% vs. 11.4%). PD-1.3 and PD-1.6 were less polymorphic and did not differ between the groups. Rare AA genotype of PD-1.3 (1.4% vs. 1.0%) and AG genotype of PD-1.6 was again similarly (22.4% vs. 19.2%) present in TA and HC. CONCLUSIONS: PD-1.3, 1.5 and 1.6 polymorphisms of PDCD1 gene, which were shown to be associated with various autoimmune disorders and vasculitides, are not associated with a susceptibility to TA in Turkish population.

Assessment of disease activity and progression in Takayasu's arteritis.

Takayasu's arteritis (TA) is a rare, chronic panarteritis of the aorta and its major branches presenting commonly in young ages. Physical examination findings, presence of constitutional features, elevated acute-phase reactants, and new vessel involvement in imaging are major features of an active disease. However, assessment of disease activity and damage in TA is problematic given the chronic, indolent disease course and lack of specific laboratory and imaging findings. Although CT, MRI, and FDG-PET are commonly used imaging modalities, their lack of specificity to discriminate active disease from damage, limit their usefulness in routine practice. Two recently introduced multi-systemic clinical assessment tools, the DEI.Tak and the ITAS (both derived from BVAS), seem to be helpful in assessing disease activity and damage in TA. However, physician's global assessments of disease activity and decisions regarding treatments are still strongly influenced by changes in the acute-phase response and imaging. A comprehensive approach to both systemic and vascular features of TA to define a validated set of outcome measures for use in clinical trials and clinical practice is clearly needed. The OMERACT Vasculitis Working Group has taken on this task and has embarked on a research agenda to advance outcome measure development in TA.