Harmonized analysis of PBMC by mass cytometry.

Mass cytometry permits the high dimensional analysis of cellular systems at single-cell resolution with high throughput in various areas of biomedical research. Here, we provide a state-of-the-art protocol for the analysis of human peripheral blood mononuclear cells (PBMC) by mass cytometry. We focus on the implementation of measures promoting the harmonization of large and complex studies to aid robustness and reproducibility of immune phenotyping data.

Comparing clinical profiles in spondyloarthritis with Crohn's disease or ulcerative colitis: insights from the ASAS-PerSpA study.

Objectives: Assuming SpA manifestations may vary among patients with different inflammatory bowel disease (IBD) subtypes, we explored the clinical characteristics associated with the presence of Crohn's disease (CD) or ulcerative colitis (UC) in patients with spondyloarthritis (SpA). Methods: We included 3152 patients of ASAS-PerSpA study diagnosed with either axial SpA or peripheral SpA, according to their treating rheumatologist. Of these, 146 (4.6%) had confirmed IBD by endoscopy and were categorized into CD or UC groups. Demographics, clinical characteristics, treatments and patient-reported outcomes were compared between the two subgroups. Results: From 146 patients included in the current analysis, 87 (59.6%) had CD [75 (86.2%) axial SpA and 12 (13.8%) peripheral SpA], and 39 (26.7%) had UC [34 (87.2%) axial SpA and 5 (12.8%) peripheral SpA]. CD and UC groups had similar age with average of 44.9 (13.5) vs 44.0 (13.0) years, respectively, and a slight male predominance in CD (63.2%) compared with UC (51.3%). Diagnostic delay for SpA was 7.0 (6.9) years for CD and 8.8 (8.1) years for UC. Chronic back pain was the most reported symptom present in 95.4% of CD patients and 89.7% of UC patients. Both groups had similar musculoskeletal phenotyping, with higher frequency of psoriasis (15.4%) and uveitis 28.2% in UC; and higher tendency to be HLA-B27 positive in CD (51.9% in CD vs.s 39.4% in UC). Conclusion: In our analysis patients with SpA and concurrent CD or UC had mainly similar musculoskeletal phenotypes. However, they differ slightly in extra-musculoskeletal manifestations and HLA-B27 prevalence.

Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Diagnostic accuracy in axial spondyloarthritis: a systematic evaluation of the role of clinical information in the interpretation of sacroiliac joint imaging.

OBJECTIVES: Radiography and MRI of the sacroiliac joints (SIJ) are relevant for the diagnosis and classification of patients with axial spondyloarthritis (axSpA). This study aimed to evaluate the impact of clinical information (CI) on the accuracy of imaging interpretation. METHODS: Out of 109 patients referred because of suspicion of axSpA with complete imaging sets (radiographs and MRI of SIJ), 61 were diagnosed with axSpA (56%). Images were independently evaluated by three radiologists in four consecutive reading campaigns: radiographs and radiographs+MRI without and with CI including demographic data, SpA features, physical activity and pregnancy. Radiographs were scored according to the modified New York criteria, and MRIs for inflammatory and structural changes compatible with axSpA (yes/no). The clinical diagnosis was taken as reference standard. The compatibility of imaging findings with a diagnosis of axSpA (precision) before and after the provision of CI and radiologists' confidence with their findings (0-10) were evaluated. RESULTS: The precision of radiographs evaluation without versus with CI increased from 70% to 78% (p=0.008), and for radiographs+MRI from 81% to 82% (p=1.0), respectively. For CR alone, the sensitivity and specificity of radiologic findings were 51% and 94% without and 60% and 100% with CI, while, for radiographs+MRI, they were 74% and 90% vs 71% and 98%, respectively. The diagnostic confidence of radiologists increased from 5.2±1.9 to 6.0±1.7 with CI for radiographs, and from 6.7±1.6 to 7.2±1.6 for radiographs+MRI, respectively. CONCLUSION: The precision, specificity and diagnostic confidence of radiologic evaluation increased when CI was provided.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

OBJECTIVE: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. METHODS: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. RESULTS: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. CONCLUSIONS: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Learning imaging in axial spondyloarthritis: more than just a matter of experience.

OBJECTIVE: Reliable interpretation of imaging findings is essential for the diagnosis of axial spondyloarthritis (axSpA) and requires a high level of experience. We investigated experience-dependent differences in diagnostic accuracies using X-ray (XR), MRI and CT. METHODS: This post hoc analysis included 163 subjects with low back pain. Eighty-nine patients had axSpA, and 74 patients had other conditions (mechanical, degenerative or non-specific low back pain). Final diagnoses were established by an experienced rheumatologist before the reading sessions. Nine blinded readers (divided into three groups with different levels of experience) scored the XR, CT and MRI of the sacroiliac joints for the presence versus absence of axSpA. Parameters for diagnostic performance were calculated using contingency tables. Differences in diagnostic performance between the reader groups were assessed using the McNemar test. Inter-rater reliability was assessed using Fleiss kappa. RESULTS: Diagnostic performance was highest for the most experienced reader group, except for XR. In the inexperienced and semi-experienced group, diagnostic performance was highest for CT&MRI (78.5% and 85.3%, respectively). In the experienced group, MRI showed the highest performance (85.9%). The greatest difference in diagnostic performance was found for MRI between the inexperienced and experienced group (76.1% vs 85.9%, p=0.001). Inter-rater agreement was best for CT in the experienced group with κ=0.87. CONCLUSION: Differences exist in the learnability of the imaging modalities for axSpA diagnosis. MRI requires more experience, while CT is more suitable for inexperienced radiologists. However, diagnosis relies on both clinical and imaging information.

Association of nociplastic and neuropathic pain components with the presence of residual symptoms in patients with axial spondyloarthritis receiving biological disease-modifying antirheumatic drugs.

OBJECTIVE: To evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: 78 patients with r-axSpA from the GErman SPondyloarthritis Inception Cohort receiving a bDMARD for at least 3 months were included in this analysis. The Widespread Pain Index (WPI) and the PainDETECT (PD) questionnaire were used to quantify the NoP and the NP components, respectively. Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used as measures of residual symptoms. C reactive protein (CRP) was used as a measure of systemic inflammatory activity. Univariable and multivariable regression analyses of disease activity were performed. The regions of the WPI score and items of the PD score were used for cluster analyses. RESULTS: Linear multivariable regression analysis showed that WPI and PD were independently associated with ASDAS (b=0.1, 95% CI 0.04 to 0.17, and b=0.05, 95% CI 0.02 to 0.08, respectively) and BASDAI (b=0.24, 95% CI 0.08 to 0.39, and b=0.17, 95% CI 0.1 to 0.25, respectively) in r-axSpA patients receiving stable treatment with bDMARDs. Furthermore, WPI and PD were found to be significantly associated with the presence of relevant residual symptoms as defined by BASDAI ≥4 (OR 1.93, 95% CI 1.09 to 4.15, and OR 1.32, 95% CI 1.04 to 1.85, respectively). The effects were present also in patients with normal level of CRP. Cluster analysis revealed three distinct pain distribution profiles and four specific sensory symptom constellations allowing differentiation of different pain subtypes. CONCLUSION: Both NoP and NP components seem to be associated with residual symptoms in patients with r-axSpA receiving treatment with bDMARDs.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn's Disease.

OBJECTIVE: Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology. METHODS: We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal. RESULTS: We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia. CONCLUSION: Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27.

HLA-B27-positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management, and treatment.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Self-reported diagnostic confidence predicts diagnostic accuracy in axial spondyloarthritis imaging.

OBJECTIVES: Reporting diagnostic confidence (DC) in axial spondyloarthritis (axSpA) imaging is recommended by the ASAS guidelines. Our aim was to investigate whether self-reported DC predicts diagnostic accuracy in axSpA imaging using X-ray (XR), computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: We performed a post hoc analysis including 163 patients with low back pain (89 axSpA and 56 non-axSpA). Nine blinded readers with different experience levels (inexperienced (< 1 year), semi-experienced (3-8 years) and experienced (> 12 years)) scored the sacroiliac joint images for compatibility with axSpA. DC was reported on a scale from 1 (not sure) to 10 (very sure). Mean DC scores and standard deviations were calculated for correct and incorrect responses using XR, CT, MRI, XR+MRI and CT+MRI. Differences in DC were assessed using the Mann-Whitney U test. RESULTS: DC scores were higher for correct axSpA diagnoses and differed significantly between correct and incorrect responses for all modalities (p< 0.001), with a mean DC of 7.1 ± 2.1 and 6.3 ± 2.1 for XR, 8.3 ± 1.8 and 6.7 ± 2.0 for CT, 8.1 ± 1.9 and 6.2 ± 1.9 for MRI, 8.2 ± 1.8 and 6.7 ± 1.8 for XR+MRI and 8.4 ± 1.8 and 6.8 ± 1.8 for CT+MRI, respectively. This was also the case when looking at the results by experience group, except for XR in the inexperienced group. CONCLUSION: Providing self-reported DC in radiological reports is useful information to predict diagnostic reliability in axSpA imaging.

Sex-specific diagnostic efficacy of MRI in axial spondyloarthritis: challenging the 'One Size Fits All' notion.

OBJECTIVES: Sex-specific differences in the presentation of axial spondyloarthritis (axSpA) may contribute to a diagnostic delay in women. The aim of this study was to investigate the diagnostic performance of MRI findings comparing men and women. METHODS: Patients with back pain from six different prospective cohorts (n=1194) were screened for inclusion in this post hoc analysis. Two blinded readers scored the MRI data sets independently for the presence of ankylosis, erosion, sclerosis, fat metaplasia and bone marrow oedema. Χ2 tests were performed to compare lesion frequencies. Contingency tables were used to calculate markers for diagnostic performance, with clinical diagnosis as the standard of reference. The positive and negative likelihood ratios (LR+/LR-) were used to calculate the diagnostic OR (DOR) to assess the diagnostic performance. RESULTS: After application of exclusion criteria, 526 patients (379 axSpA (136 women and 243 men) and 147 controls with chronic low back pain) were included. No major sex-specific differences in the diagnostic performance were shown for bone marrow oedema (DOR m: 3.0; f: 3.9). Fat metaplasia showed a better diagnostic performance in men (DOR 37.9) than in women (DOR 5.0). Lower specificity was seen in women for erosions (77% vs 87%), sclerosis (44% vs 66%), fat metaplasia (87% vs 96%). CONCLUSION: The diagnostic performance of structural MRI markers is substantially lower in female patients with axSpA; active inflammatory lesions show comparable performance in both sexes, while still overall inferior to structural markers. This leads to a comparably higher risk of false positive findings in women.

HLA-B27 status and inflammatory MRI lesions of the sacroiliac joints: a post hoc analysis in patients without axial spondyloarthritis.

OBJECTIVE: The assessment of inflammatory and structural lesions in the sacroiliac joint (SIJ) is crucial in axial spondyloarthritis (axSpA). HLA-B27 status plays an important role in axSpA diagnosis and has been linked to MRI lesion burden in the general population. We aimed to investigate the sex-specific influence of HLA-B27 status on inflammatory and structural MRI findings in patients with low back pain of non-inflammatory origin. METHODS: This post hoc analysis included 139 non-axSpA patients (90 women) with chronic low back pain. Two readers scored MRIs of the SIJ for the presence of sclerosis, erosion, fat metaplasia, bone marrow oedema (BMO) and ankylosis. Frequencies and extent of lesions were compared regarding the HLA-B27 status using χ2 tests and t-tests. Regression models to assess the sex-dependent influence of HLA-B27 on lesion burden were computed. RESULTS: HLA-B27 was positive in 33 women (36.7%) and 23 men (46.9%). The overall occurrence of all SIJ lesions did not differ in HLA-B27 negative and positive individuals. There were no significant differences in the extent of lesions considering the HLA-B27 positivity, for erosion (mean sum score (MSS) of 0.91 vs 0.48; p=0.144), sclerosis (MSS 1.65 vs 1.88; p=0.576), fat metaplasia (MSS 0.56 vs 0.27; p=0.425), BMO (MSS 0.75 vs 0.59; p=0.460) and ankylosis (MSS 0.06 vs 0.04; p=0.659). CONCLUSION: HLA-B27 status has no significant influence on the occurrence and extent of SIJ lesions in patients with low back pain of non-inflammatory origin in either men or women.

[HLA-B27 positive anterior uveitis : Clinical aspects, diagnostics, interdisciplinary management and treatment]. / HLA-B27-positive Uveitis anterior : Klinik, Diagnostik, interdisziplinäres Management und Therapie.

Acute anterior uveitis (AAU) associated with human leukocyte antigen (HLA) B27 is the most common form of noninfectious intraocular inflammation and is considered to be a separate clinical entity. Young adults between the ages of 20 and 40 years are predominantly affected. The HLA-B27 positive AAU typically presents as a unilateral, fulminant disruption of the blood-aqueous humor barrier, which is accompanied by pronounced cellular infiltration and fibrinous exudation. Other characteristics are reduced intraocular pressure and a high tendency to relapse, which can also involve the partner eye. Patients with HLA-B27 positive AAU share a high risk for other genetically associated diseases, especially spondylarthritis, chronic inflammatory bowel diseases and psoriasis. As up to 40% of those affected have a systemic disease that has not yet been diagnosed, the ophthalmologist is of major importance for early detection.

Anatomical variation of the sacroiliac joint carries an increased risk for erosion and bone marrow oedema in axial spondyloarthritis.

OBJECTIVES: To assess the impact of joint shape variations on inflammatory lesions on SI joint MRIs in patients with axial spondyloarthritis (axSpA). METHODS: A total of 1194 patients from four different prospective cohorts were evaluated, with 684 (57.3%) having sufficient imaging data for inclusion (379 axSpA, 305 controls). All images were evaluated for joint form, erosion, sclerosis, fat metaplasia and bone marrow oedema (BMO) by two independent readers. Logistic regression analyses were used to assess the association of joint form and lesions on imaging for axSpA patients and controls. RESULTS: Atypical joint forms were common in both axSpA (43.5% [154/354]) and control patients (44.2% [134/303]); both intra-articular variants and a crescent joint shape were significantly more common in axSpA patients (18.4% vs 11.6% and 11.0% vs 5.3.%, respectively; P < 0.001). The axSpA patients with intra-articular joint form variants had 2-fold higher odds of exhibiting erosions [odds ratio (OR) 2.09 (95% CI 1.18, 3.69)] and BMO [OR 1.79 (95% CI 1.13, 2.82)]; this association was not observed in controls. Accessory joints increased the odds for sclerosis in axSpA patients [OR 2.54 (95% CI 1.10, 5.84)] and for sclerosis [OR 17.91 (95% CI 6.92, 46.37)] and BMO [OR 2.05 (95% CI 1.03, 4.07)] in controls. CONCLUSIONS: Joint form variations are associated with the presence of inflammatory lesions on SI joint MRIs of axSpA patients. This should be taken into consideration in future research on the interplay of mechanical strain and inflammation in axSpA.

Management of Concomitant Inflammatory Bowel Disease or Uveitis in Patients with Psoriatic Arthritis: An Updated Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.

Keep an Eye on the Back: Spondyloarthritis in Patients With Acute Anterior Uveitis.

OBJECTIVES: This study was undertaken to analyze the prevalence of spondyloarthritis (SpA) in patients with acute anterior uveitis (AAU), to identify parameters associated with the presence of SpA, and to evaluate the performance of referral algorithms for identifying patients with a high probability of having SpA. METHODS: Prospectively recruited consecutive patients with noninfectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of the sacroiliac joints, allowing a definitive diagnosis/exclusion of concomitant SpA. Fisher's exact test and Mann-Whitney U test were used to compare AAU patients with SpA and AAU patients without SpA. Furthermore, logistic regression analyses were performed. The predictive performance of SpA referral strategies was analyzed by calculating the sensitivity, specificity, positive predictive value, and positive and negative likelihood ratios. RESULTS: Among the 189 AAU patients evaluated, 106 (56%) were diagnosed as having SpA. The majority of SpA patients (93%) had predominantly axial SpA and 7 patients had peripheral SpA. In 74 patients (70%), the SpA diagnosis was established for the first time. In multivariable logistic regression analysis, psoriasis (odds ratio [OR] 12.5 [95% confidence interval (95% CI) 1.3-120.2]), HLA-B27 positivity (OR 6.3 [95% CI 2.4-16.4]), elevated C-reactive protein level (OR 4.8 [95% CI 1.9-12.4]), and male sex (OR 2.1 [95% CI 1.1-4.2]) were associated with the presence of SpA. None of the ophthalmologic parameters were found to be predictive of SpA. The Dublin Uveitis Evaluation Tool (DUET) showed higher specificity for SpA recognition than the Assessment of SpondyloArthritis international Society (ASAS) tool for the early referral of patients with a suspected diagnosis of axial SpA (specificity for SpA 42% versus 28%), whereas the sensitivity of the ASAS tool was slightly higher than the DUET tool (sensitivity for SpA 80% versus 78%). However, more than 20% of the AAU patients in this study who were diagnosed as having SpA would have been missed by both referral strategies. CONCLUSION: Our study revealed a high prevalence of SpA in AAU patients overall, as well as a high prevalence of previously undiagnosed SpA in AAU patients. Therefore, we propose rheumatologic evaluation for all AAU patients with musculoskeletal symptoms.

Evaluation of the Disease Activity index for PSoriatic Arthritis (DAPSA) with a quick quantitative C reactive protein assay (Q-DAPSA) in patients with psoriatic arthritis: a prospective multicentre cross-sectional study.

OBJECTIVES: This study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA). METHODS: The assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen's kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores. RESULTS: Altogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen's kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen's kappa of 0.932 (95% CI 0.885 to 0.980). CONCLUSIONS: The Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

Antigen-specific immune reactions by expanded CD8+ T cell clones from HLA-B*27-positive patients with spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disease that is tightly linked to HLA-B*27 but the pathophysiological basis of this link is still unknown. It is discussed whether either the instability of HLA-B*27 molecules triggers predominantly innate immune reactions or yet unknown antigenic peptides presented by HLA-B*27 induce adaptive autoimmune reactions by CD8+ T cells. To analyze the pathogenesis of SpA, we here investigated the T cell receptor (TCR) usage and whole transcriptomes of CD8+ single cells from synovial fluid of HLA-B*27-positive SpA patients and HLA-B*27-negative controls. In HLA-B*27-positive patients, we confirmed preferential expression of several TCR ß-chain families, found even more restricted usage of particular TCR α-chains, assigned matching TCR αß-chain pairs with homologous CDR3-sequences, and detected identical TCR-chains in different patients. Gene expression analyses by single cell mRNAseq revealed that genes specific for the tissue resident memory phenotype, exhaustion, and apoptosis were particularly highly expressed in expanded clonotypes from HLA-B*27-positive SpA patients. Together, several independent lines of evidence argue in favor of an (auto)antigenic peptide related pathogenesis.