Tissue-Resident Memory CD8+ T Cells From Skin Differentiate Psoriatic Arthritis From Psoriasis.

OBJECTIVE: To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. METHODS: In-depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high-throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. RESULTS: Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin-17A (IL-17A) and IL-22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin-homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue-resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up-regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22-like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. CONCLUSION: Tissue-resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.

Construct validity of the ASAS health index in psoriatic arthritis: a cross-sectional analysis.

OBJECTIVES: The Assessment of SpondyloArthritis international Society health index (ASAS-HI) was designed to assess the global health of patients with spondyloarthritis, but its performance in psoriatic arthritis (PsA) is hardly known. We addressed the clinimetric properties of this instrument in patients with PsA. METHODS: This was a cross-sectional observational study that included 90 consecutive patients with PsA. The measurement properties of ASAS-HI were analysed against the Disease Activity index for PSoriatic Arthritis (DAPSA) and the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A multivariate analysis was performed to weigh the ASAS-HI items associated with DAPSA active disease and PsAID high impact. RESULTS: Mean ASAS-HI was 5.8 (4.3). Convergent validity was high both against DAPSA (ρ 0.78, P < 0.0001) and PsAID (ρ 0.80, P < 0.0001). ASAS-HI showed a high discriminant capacity for both DAPSA remission [optimal criterion ≤ 2, area under the receiver operating characteristic curve (AUC) 0.92 (95% CI: 0.85, 0.97), P < 0.0001], and low activity [optimal criterion ≤6, AUC 0.87 (95% CI: 0.79, 0.94), P < 0.0001]. The ASAS-HI items significantly associated with DAPSA active disease were: 'I find it hard to stand for long' (ß 4.48, P < 0.0001), 'I find it hard to concentrate' (ß 2.94, P = 0.042) and 'I sleep badly at night' (ß 1.86, P = 0.044). As for PsAID, the only item significantly associated with a high impact was 'I sleep badly at night' (ß -3.29, P = 0.015). CONCLUSION: We demonstrated construct validity of ASAS-HI, a spondyloarthritis instrument, for the assessment of global health in patients with PsA.

Early Achilles Enthesis Involvement in a Murine Model of Spondyloarthropathy: Morphological Imaging with Ultrashort Echo-Time Sequences and Ultrasmall Superparamagnetic Iron Oxide (USPIO) Particle Evaluation in Macrophagic Detection.

Purpose: To confirm the interest of 3-dimensional ultrashort echo-time (3D-UTE) sequences to assess morphologic aspects in normal and pathological Achilles entheses in a rat model of spondyloarthropathy (SpA) with histological correlations, in comparison with conventional RARE T2 Fat-Sat sequences, and, furthermore, to evaluate the feasibility of a 3D multiecho UTE sequence performed before and after the intravenous injection of ultrasmall superparamagnetic iron oxide (USPIO) particles to assess macrophagic involvement in the Achilles enthesis in the same rat model of SpA. Materials and Methods: Fourteen rats underwent in vivo MRI of the ankle at 4.7 T, including a 3D RARE T2 Fat-Sat sequence and a 3D ultrashort echo-time (UTE) sequence for morphologic assessment at baseline and day 3 after induction of an SpA model, leading to Achilles enthesopathy in the left paw (right paw serving as a control). A 3D multiecho UTE sequence was also performed at day 3 before and then 24 (4 rats) and 48 (2 rats) hours after intravenous injection of USPIO. Visual analysis and signal intensity measurements of all images were performed at different locations of the Achilles enthesis and preinsertional area. Visual analysis and T2∗ measurements were performed before and after USPIO injection, on the 3D multiecho UTE sequence in the same locations. Normal and pathological values were compared by Wilcoxon signed-rank tests. MR findings were compared against histological data. Results: 3D-UTE sequences enabled morphologic identification of the anterior fibrocartilage and posterior collagenic areas of the Achilles enthesis. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at day 3 (P=0.02). After administration of USPIO, no differences in signals were detected. Similarly, both visual analysis and signal T2∗ measurements in the enthesis were unable to distinguish the SpA-affected tendons from healthy ones (P=0.914). Neither the normal anatomy of the enthesis nor its pathological pattern could be distinguished using the standard RARE sequence. Histology confirmed the absence of USPIO in Achilles entheses, despite marked signs of inflammation. Conclusion: Unlike conventional RARE T2 Fat-Sat sequences, 3D-UTE sequences enable morphologic assessment of normal enthesis anatomy and early detection of abnormalities in pathological conditions. However, 3D multiecho UTE sequences combined with USPIO injections with T2∗ measurements were unable to detect macrophagic involvement in these pathological conditions.

Do we need to perform MRI of the whole spine in addition to MRI of the sacroiliac joints in suspected spondyloarthropathy?

AIM: To identify the incidence of spinal-only changes (including both acute inflammatory and chronic structural changes) in patients with suspected spondyloarthropathy (SpA) to determine whether MRI of the sacroiliac joints would be sufficient in the initial radiological work-up and whether the number of spinal magnetic resonance imaging (MRI) examinations performed could be reduced. MATERIALS AND METHODS: This was a retrospective study of patients with suspected SpA referred from the rheumatology department of a university teaching hospital undergoing MRI both of the whole spine and of the sacroiliac joints over a 3-year period. Imaging was assessed for the presence of acute inflammatory and chronic structural changes. RESULTS: Three hundred and sixty-five patients with suspected SpA undergoing both whole spine and sacroiliac joint MRI were identified. The majority (79.2%) had no spinal or sacroiliac joint inflammation. Spinal-only changes (acute inflammatory and/or chronic structural) were detected in only 0.8% (3/365) of cases. The majority of positive spinal cases had inflammatory changes involving the thoracic spine (21/24). The majority of positive sacroiliac joint cases were bilateral (51/73). CONCLUSION: The extremely low incidence of spinal-only inflammatory or structural change indicates that sacroiliac joint MRI may be sufficient for initial radiological work-up of SpA with spinal MRI reserved for instances where there is spinal symptomatology and uncertainty in the clinical diagnosis following interdisciplinary discussion or where a baseline is required.

A spontaneous model of spondyloarthropathies that develops bone loss and pathological bone formation: A process regulated by IL27RA-/- and mutant-p53.

Spondyloarthropathies, the second most frequently occurring form of chronic inflammatory arthritis, affects young adults in particular. However, a proper model with which to study the biology of this disease and to develop therapeutics is lacking. One of the most accepted animal models for this disease uses HLA-B27/Hu-ß2m transgenic rats; however, only 30%-50% of male HLA-B27/Hu-ß2m rats develop spontaneous, clinically apparent spondylitis and have a variable time until disease onset. Here, we report a high-incidence, low-variation spontaneous mouse model that delineates how the combination of inflammatory cytokine interleukin-27 (IL-27) signaling deficiency and mitogenic signaling (mutant p53R172H) in vivo, leads to bone loss in the vertebral bodies and ossification of the cartilage in the intervertebral discs. In this human disease-like mouse model, bone loss and pathogenic bone development are seen as early as 4 months of age in the absence of inflammatory aggregates in the enthesis or intervertebral disc.

Detection of Crohn Disease in Patients with Spondyloarthropathy: The SpACE Capsule Study.

OBJECTIVE: Inflammatory bowel disease (IBD) is generally reported to be associated with spondylarthropathies (SpA) in 5%-15% of cases. Systematic colonoscopic assessment by protocol demonstrated mucosal inflammation characteristic of Crohn disease (CD) in up to one-third of patients with SpA. Video capsule endoscopy (CE) is a superior diagnostic tool to detect small bowel mucosal disease. Our study compared the accuracy of CE to standard colonoscopy for detection of inflammatory bowel lesions in patients with SpA, and to describe predictors of small bowel inflammation (SBI) in this cohort. METHODS: Prospective cross-sectional study of adult patients followed for SpA. Patients were evaluated by CE and standard colonoscopy with biopsies. SBI was quantified using the Lewis Score. Additional screening tests included fecal calprotectin (FCP), C-reactive protein (CRP), and a diagnostic panel of serologic, inflammatory and genetic tests (SGI). RESULTS: There were 64 patients recruited (53% female, mean age 42 ± 13 yrs). Chronic gastrointestinal (GI) symptoms were present in 57%. CE revealed significant SBI in 27/64 (42.2%), compared to 7/64 (10.9%) by standard colonoscopy (p = 0.035). Elevated FCP was associated with small bowel CD (OR 4.5, 95% CI 1.01-19.9; p = 0.042). No correlation was observed with presence of GI symptoms, CRP, or SGI results. Finding CD led to a change in management in 65.2% of cases. CONCLUSION: CE uncovered SBI consistent with CD in 42.2% of patients with SpA, with a significant incremental yield over colonoscopy of 31%. FCP levels were significantly correlated with CE results, while GI symptoms and SGI results were poor predictors of SBI.

Role of Stem Cells in Pathophysiology and Therapy of Spondyloarthropathies-New Therapeutic Possibilities?

Considerable progress has been made recently in understanding the complex pathogenesis and treatment of spondyloarthropathies (SpA). Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although they adequately control inflammatory symptoms, they do not affect the abnormal bone formation processes associated with SpA. However, the traditional therapeutic approach does not cover the regenerative treatment of damaged tissues. In this regards, stem cells may offer a promising, safe and effective therapeutic option. The aim of this paper is to present the role of mesenchymal stromal cells (MSC) in pathogenesis of SpA and to highlight the opportunities for using stem cells in regenerative processes and in the treatment of inflammatory changes in articular structures.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using Pharmacokinetic Modeling: Initial Experience in Patients With Early Arthritis.

OBJECTIVE: Analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using pharmacokinetic modeling (PKM) provides quantitative measures that mirror microvessel integrity and can be used as an objective marker of the level of synovial inflammation. The aim of this study was to investigate the PKM parameters K(trans) , kep , and ve in a prospective cohort of disease-modifying antirheumatic drug (DMARD)-naive patients with early arthritis, and to validate the results by assessing their correlation with the number of synovial endothelial cells (ECs). METHODS: Forty-seven patients with early arthritis (arthritis duration <1 year, DMARD naive; comprising 14 patients with rheumatoid arthritis, 22 with unclassified arthritis, 6 with spondyloarthritis [SpA], and 5 with other arthritides) were included. At baseline, DCE-MRI was performed on an inflamed knee joint of each patient. These images were used to calculate the K(trans) (volume transfer constant between the plasma and extracellular extravascular space [EES]), the kep (transfer constant between the EES and plasma), and the ve (fractional volume of the EES). Second, markers of disease activity were collected. Finally, vascularity was evaluated by immunohistochemical analysis of synovial tissue samples obtained from the inflamed knee joints, using antibodies to detect von Willebrand factor (vWF), a marker of ECs. RESULTS: The 3 PKM parameters differed significantly between diagnostic groups at baseline, with the highest K(trans) value being observed in patients with SpA (median 0.050/minute, interquartile range [IQR] 0.041- 0.069). Furthermore, the K(trans) , kep , and ve values correlated significantly with markers of disease activity. Finally, the PKM parameters K(trans) and kep , but not ve , correlated significantly with synovial expression of vWF (r = 0.647, P = 0.004 for K(trans) ; r = 0.614, P = 0.007 for kep ; r = 0.398, P = 0.102 for ve ). CONCLUSION: These results suggest that the K(trans) , kep , and ve can be used to detect synovial inflammation in patients with early arthritis, and these PKM parameters may be helpful in differential diagnosis. This approach may also be useful in translational research analyzing tissue microcirculation and angiogenesis.

Associations Between Spondyloarthritis Features and Magnetic Resonance Imaging Findings: A Cross-Sectional Analysis of 1,020 Patients With Persistent Low Back Pain.

OBJECTIVE: The Assessment of SpondyloArthritis international Society (ASAS) has previously published criteria for spondyloarthritis (SpA). In the Spines of Southern Denmark cohort, which included patients with persistent low back pain and an unknown proportion of patients with SpA, our objectives were 1) to estimate the prevalence of magnetic resonance imaging (MRI) findings and clinical features included in the ASAS criteria for SpA and 2) to explore the associations between MRI findings and clinical features. METHODS: We included patients ages 18-40 years with persistent low back pain who had been referred to the Spine Centre of Southern Denmark. We collected information on clinical features (including HLA-B27 and high-sensitivity C-reactive protein) and MRI findings in the spine and sacroiliac (SI) joints. RESULTS: Of 1,020 included patients, 537 (53%) had at least 1 of the clinical features included in the ASAS criteria for SpA. Three clinical features were common-inflammatory back pain according to the ASAS criteria, a good response to nonsteroidal antiinflammatory drugs (NSAIDs), and family history of SpA. The prevalence of these features ranged from 15% to 17%. Sacroiliitis on MRI according to the ASAS definition was present in 217 patients (21%). Of those 217 patients, 91 (42%) had the minimum amount of bone marrow edema required according to the ASAS definition (a low bone marrow edema score). The presence of HLA-B27, peripheral arthritis, a good response to NSAIDs, and preceding infection were independently positively associated with MRI findings in the SI joints (odds ratios [ORs] of 1.9-9.0). The remaining 8 clinical features were not positively associated with MRI findings. Importantly, only age was independently associated with low bone marrow edema score at the SI joints (OR of 1.1 per year). CONCLUSION: In this population, 53% had at least 1 clinical feature included in the ASAS criteria for SpA, and 21% had sacroiliitis according to the ASAS definition; furthermore, the associations between the clinical and imaging domains were inconsistent. The results indicate a need for further investigation of the importance of these findings in SpA, including investigation of the minimum requirements for defining sacroiliitis on MRI.

Course of Magnetic Resonance Imaging-Detected Inflammation and Structural Lesions in the Sacroiliac Joints of Patients in the Randomized, Double-Blind, Placebo-Controlled Danish Multicenter Study of Adalimumab in Spondyloarthritis, as Assessed by the Berlin and Spondyloarthritis Research Consortium of Canada Methods.

OBJECTIVE: To investigate changes in magnetic resonance imaging (MRI)-assessed inflammation and structural lesions in the sacroiliac (SI) joints during treatment with adalimumab versus placebo. METHODS: In a 48-week double-blind, placebo-controlled trial, 52 patients with spondyloarthritis were randomized to receive subcutaneous injections of either adalimumab 40 mg (n = 25) or placebo (n = 27) every other week for 12 weeks. Patients in the adalimumab group continued to receive and patients in the placebo group were switched to adalimumab 40 mg every other week for an additional 12 weeks. MRI of the SI joints was performed at weeks 0, 12, 24, and 48, and the images were assessed independently in a blinded manner using the modified Berlin and the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI scores for inflammation and structural lesions of the SI joints. RESULTS: At baseline, 56% of the adalimumab group and ∼72% of the placebo group had an MRI-assessed inflammation score of ≥1. Among the patients with inflammation at baseline, the mean percent reductions in MRI scores for inflammation from week 0 to 12 were greater in the adalimumab group compared with the placebo group (Berlin method, -62% versus -5%; SPARCC method, -58% versus -12% [both P < 0.04]). Furthermore, the mean SPARCC erosion score decreased (-0.6) and the SPARCC backfill score increased (+0.8) in the adalimumab group from week 0 to week 12. From week 12 to week 24, larger absolute reductions in the Berlin/SPARCC inflammation scores and the SPARCC erosion score and larger increases in the Berlin/SPARCC fatty lesion scores were seen in the placebo group compared with the adalimumab group. In univariate regression analyses (analysis of covariance) and multivariate stepwise regression analyses, treatment with adalimumab was independently associated with regression of the SPARCC erosion score from week 0 to 12 but not with changes in the other types of MRI lesions. CONCLUSION: Significant changes in the Berlin and SPARCC MRI-assessed inflammation scores and in the SPARCC MRI-assessed erosion scores occurred within 12 weeks after initiation of adalimumab. Tumor necrosis factor inhibitor treatment was associated with resolution of erosions and the development of backfill.

Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis.

OBJECTIVES: Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). CD161/LLT1 ligation may co-stimulate T-cell IFN-γ production. We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid (SF) and synovial tissue (ST). We also assessed levels of soluble LLT1 (sLLT1) in different phases of RA development. METHODS: Paired samples of peripheral blood mononuclear cells (MC) and SFMC (n = 14), digested ST cells (n = 4) and ST paraffin sections (n = 6) from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26), recently diagnosed RA patients (n = 39), seropositive arthralgia patients (SAP, n = 31), spondyloarthropathy patients (SpA, n = 26) and healthy controls (HC, n = 31) were assayed. RESULTS: In RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups. CONCLUSIONS: In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy) when compared to healthy subjects.

Do real ao ideal - o (des)cuidar da saúde dos idosos longevos / El real a lo ideal - el (des)cuidado de la salud de los más ancianos / From real to ideal - the health (un)care of long-lived elders

RESUMOObjetivo:analisar semelhanças e dessemelhanças nos significados do cuidado à saúde de idosos longevos atribuídos por eles e pelos profi ssionais de enfermagem no cenário de uma unidade básica de saúde.Método:pesquisa qualitativa etnográfica, alicerçada no método de Spradley e McCurdy e na antropologia interpretativa de Geertz e Kleinman. Participaram 20 informantes-chaves, as informações foram coletadas por meio da observação participante e entrevista etnográfica no período de março a outubro de 2013 e analisadas em domínios, taxonomias e tema cultural.Resultados:emergiram seis domínios e taxonomias culturais que mostraram razões, atributos e recursos para cuidar, na perspectiva dos idosos e dos profissionais de enfermagem e, por fim, o tema cultural: do real ao ideal - o (des)cuidar da saúde dos idosos longevos.Conclusão:o estudo mostrou o distanciamento entre o cuidado almejado e o realizado à saúde das pessoas com idade mais avançada no cenário estudado.

RESUMENObjetivo:analizar las similitudes y diferencias en los signifi cados del cuidado de salud para los más ancianos asignado por ellos y los profesionales de enfermería en un unidad básica de salud.Método:investigación cualitativa etnográfi ca, basado en método de Spradley y McCurdy y la antropología interpretativa de Geertz y Kleinman. Participaron 20 informantes clave y los datos fueron recolectados a través de la observación participante y entrevistas etnográfi cas en período de marzo a octubre de 2013 y analizados en dominios, taxonomías y tema cultural.Resultados:surgieron seis dominios y taxonomías culturales que mostraron las razones, atributos y recursos para cuidar, en perspectiva de los más ancianos y profesionales de enfermería; fi nalmente, el tema cultural: el real a lo ideal - el (des)cuidado de la salud de los más ancianos.Conclusión:el estudio demostró la distancia entre el cuidado de la salud deseado y real de las personas con edad avanzada en el escenario estudiado.

ABSTRACTObjective:to analyze similarities and dissimilarities in the meanings assigned to health care by long-lived elders and nursing professionals in a healthcare setting.Method:ethnographic qualitative research, based on the Spradley-McCurdy method and the interpretive anthropology of Geertz and Kleinman. The sample consisted of 20 key informants. Data were collected through participatory observation and ethnographic interviews from March to October 2013 and analyzed in domains, taxonomies and cultural themes.Results:Six domains and cultural taxonomies emerged and revealed reasons, attributes, and resources in providing care in relationship to long-lived elders and nursing professionals; fi nally, the following cultural theme emerged: the real to the ideal - the health (un)care of long-lived elders.Conclusion:The study showed the distance between the desired and actual health care provided to aged people in the scenario studied.

Vasoactive Intestinal Peptide in Early Spondyloarthritis: Low Serum Levels as a Potential Biomarker for Disease Severity.

Spondyloarthritis (SpA) is a family of inflammatory diseases sharing clinical, genetic, and radiological features. While crucial for tailoring early interventions, validated prognostic biomarkers are scarce in SpA. We analyze the correlation between serum levels of vasoactive intestinal peptide (VIP) and disease activity/severity in patients with early chronic inflammatory back pain. The study population comprised 54 patients enrolled in our early chronic inflammatory back pain register. We collected demographic information, clinical data, laboratory data, and imaging findings. VIP levels were measured by enzyme immunoassay in serum samples from 162 visits. The association between independent variables and VIP levels was analyzed using longitudinal multivariate analysis nested by patient and visit. No significant differences were observed in VIP levels between these two groups. Lower levels of VIP were significantly associated with a higher Bath Ankylosing Spondylitis Disease Activity Index (BASFI) score, presence of bone edema in magnetic resonance imaging (MRI) scan, and lower hemoglobin levels. Coexistence of cutaneous psoriasis was independently associated with lower VIP levels, and similar trend was observed for enthesitis. We conclude that SpA patients with low serum VIP levels had worse 2-year disease outcome, suggesting that serum VIP levels could be a valid prognostic biomarker.

Increased expression of human leucocyte antigen class I free heavy chains on monocytes of patients with spondyloarthritis and cells transfected with HLA-B27.

Human leucocyte antigen (HLA)-B27 expression is correlated with spondyloarthritis (SpA), but its role in disease pathogenesis remains unclear. The aim of the study was to determine whether HLA-B27 free heavy chain (FHC) contributes to SpA pathogenesis. Flow cytometry was used to analyse the FHC expression on CD3+ and CD14+ cells in the peripheral blood (PB) and synovial fluid (SF) from SpA patients, healthy controls, and rheumatoid arthritis (RA) patients. Human monocytic U937 cell lines stably expressing enhanced green fluorescence protein (EGFP)/HLA-B27, EGFP/HLA-A2 or EGFP alone were created to further investigate the relation between HLA-B27 and FHC expression. The relative FHC level on CD14+ PB cells was significantly higher in SpA patients than in controls, but lower than on the SF cells of SpA patients. No significant correlation was found for relative FHC expression with HLA-B27 or ß2-microglobulin expression. HLA-B27-transfected U937 cells expressed higher FHC levels than either EGFP/HLA-A2- or EGFP-transfected cells. HLA class I FHC expression was significantly increased on monocytes of SpA patients and HLA-B27-transfected cells, implying that FHC, perhaps mostly derived from HLA-B27, plays an important role in SpA pathogenesis.

Candidate lesion-based criteria for defining a positive sacroiliac joint MRI in two cohorts of patients with axial spondyloarthritis.

OBJECTIVE: To determine candidate lesion-based criteria for a positive sacroiliac joint (SIJ) MRI based on bone marrow oedema (BMO) and/or erosion in non-radiographic axial spondyloarthritis (nr-axSpA); to compare the performance of lesion-based criteria with global evaluation by expert readers. METHODS: Two independent cohorts A/B of 69/88 consecutive patients with back pain aged ≤50 years, with median symptom duration 1.3/10.0 years, were referred for suspected SpA (A) or acute anterior uveitis plus back pain (B). Patients were classified according to rheumatologist expert opinion based on clinical examination, pelvic radiography and laboratory values as having nr-axSpA (n=51), ankylosing spondylitis (n=34) or non-specific back pain (n=72). Four blinded readers assessed SIJ MRI, recording the presence/absence of SpA by concomitant global evaluation of T1-weighted spin echo (T1SE) and short τ inversion recovery (STIR) scans and, thereafter, whether BMO and/or erosion were present/absent in each SIJ quadrant of each MRI slice. We derived candidate lesion-based criteria based on the number of SIJ quadrants with BMO and/or erosion and calculated mean sensitivity and specificity for SpA. RESULTS: For both cohorts A/B, global assessment showed high specificity (0.95/0.83) compared with the Assessment in SpondyloArthritis international Society (ASAS) definition (0.76/0.74). BMO ≥3 (0.89/0.84) or ≥4 (0.92/0.87) showed comparably high specificity to global assessment. Erosion ≥2 and/or BMO ≥3 or ≥4 were associated with comparably high sensitivity to global assessment without affecting specificity. These combined criteria showed both higher sensitivity and specificity than the ASAS definition. CONCLUSIONS: Lesion-based criteria for a positive SIJ MRI based on both BMO and/or erosion performed best for classification of axial SpA, reflecting the contextual information provided by T1SE and STIR sequences.

Diagnostic utility of magnetic resonance imaging and radiography in juvenile spondyloarthritis: evaluation of the sacroiliac joints in controls and affected subjects.

OBJECTIVE: To compare the utility of radiography and magnetic resonance imaging (MRI) for the diagnosis of juvenile-onset spondyloarthritis in pediatric patients presenting with low back and/or sacroiliac (SI) pain of potentially inflammatory etiology. METHODS: Radiographs and MRI studies of the SI joints in 26 patients with juvenile spondyloarthritis (JSpA) and 35 controls were assessed independently by 2 radiologists, with discrepancies arbitrated by a third. Radiographs and MRI were blinded and read in separate batches in random order. RESULTS: Erosion was common and was the most useful diagnostic feature on radiography [positive likelihood ratio (LR) = 3.5] and was especially diagnostic of SpA on MRI (LR = 6.7). Subchondral sclerosis was common but was the least specific feature for both modalities. Joint space narrowing had some utility on radiography (LR = 2.0) and MRI (LR = 2.7) but was uncommon and had poor reader reliability. Bone marrow edema (LR = 3.1) and subarticular fat infiltration (LR = 4.5), detectable only on MRI, were both useful features. Global diagnostic impression of MRI (LR = 9.4) had very high utility for the diagnosis of JSpA, exceeding radiography (LR = 4.4) because of superior specificity. In addition, global diagnosis of SpA is much more reliably made on MRI (κ = 0.80) compared to radiography (κ = 0.30). CONCLUSION: Specificity and reliability of MRI of the SI joints are superior to radiography for the diagnosis of juvenile-onset SpA and, where available, MRI should replace radiography as the first line of investigation.

Arthritis in a glyptodont (Mammalia, Xenarthra, Cingulata).

Arthritic lesions have been frequently diagnosed in the fossil record, with spondyloarthropathy (a type of erosive and pan-mammalian arthritis) being one of the most common types described to date for mammals, though not restricted to this group. Here, we identify spondyloarthropathy in fossil bones from the late Pleistocene in Brazil assignable to a large glyptodont individual. Bone erosions in the peripheral joints (viz., the ulna, radius, left femur and tibiae-fibulae) associated with osteosclerosis allow the diagnosis of spondyloarthropathy. The presence of osteophytes in seven bones of the forelimbs (viz., the ulna and radius) and hind limbs (viz., the tibiae-fibulae, left femur and patellae) and a subchondral cyst in one element (viz., the left femur) indicate secondary osteoarthritis. A calcified deposition on the articular surface of the left patella indicates the presence of calcium pyrophosphate deposition disease, which, like the observed osteoarthritic alterations, likely represents a complication of spondyloarthropathy. This is the first report of spondyloarthropathy for xenarthrans.