Immunogenetic Study in Chinese Population with Ankylosing Spondylitis: Are There Specific Genes Recently Disclosed?

Purpose. Ankylosing spondylitis (AS) is a systemic, autoimmune disease resulting in the destruction of the affected joints. Over the past 5 years, several new genes or genetic regions associated with AS have been identified in the Chinese population. This paper aims to discuss the major findings and related potential mechanisms of these studies in our population. Recent Findings. In recent years, due to the rapid advances in computational genetics and technology, there has been an increasing list of well-validated genes or genetic regions associated with AS susceptibility. So far, several genes or genetic regions have now been reported in the Han ethnic Chinese population, containing the major histocompatibility complex (MHC), ERAP1, IL-23R, 12q12, 2p15, 5q14.3, and so on. Different hypotheses for disease mechanisms have been investigated on the basis of the functional studies of these genes or genetic regions. Summary. This paper tries to summarize the association of several candidate genes with risk for AS in the Han ethnic Chinese population and aims to identify the novel inflammatory pathways and provide potential strategies for better therapies

The diagnostic value of morphological features of fat deposition of sacroiliac joint steatosis in axial spondyloarthritis

BackgroundFindings of fatty lesions in the context of other imaging manifestations, especially bone marrow edema and erosions can effectively assist in the diagnosis of axSpA. Chemical shift-encoded MRI is a sequence which allows for the quantification of fat signal and has been applied in the imaging evaluation of the SIJ in axSpA. The objective of this study was to investigate the diagnostic performance of morphological features of fatty lesions visualized by CSE-MRI in the imaging evaluation of SIJ in axSpA.MethodsFatty lesions with morphological features (subchondral, homogeneity and distinct border) were assessed and recorded as a binary variable in each quadrant of the SIJ. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different morphological features as well as the anatomical distribution in patients with nr-axSpA and r-axSpA. T1-weighted images and CSE-MRI fat fraction maps were directly compared in the recognition of different morphological features.ResultsEighty-two patients [non-SpA (n = 21), nr-axSpA (n = 23), r-axSpA (n = 38)] with lower back pain (LBP) were enrolled. Presence of the three morphological features of fatty lesions had a specificity of 90.48% in axSpA. The sensitivities of being subchondral, homogeneity and distinct border were 52.17, 39.13 and 39.13% in nr-axSpA on T1-weighted images. For patients with r-axSpA, the sensitivities reached 86.84, 76.32 and 57.89%. No significant difference was found in the distribution of fatty lesions between T1-weighted images and CSE-MRI. However, CSE-MRI fat fraction maps could detect significantly more fatty lesions with homogeneity (p = 0.0412) and distinct border (p = 0.0159) than T1-weighted images in the sacroiliac joint, but not subchondral lesions (p = 0.6831).ConclusionThe homogeneity and distinct border are more relevant for the diagnosis of axSpA. Moreover, CSE-MRI could detect more typical morphological features of fatty lesions than T1-weighted images in showing these two features. The presence of all three features was more likely to be indicative of axSpA

Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus

Introduction: Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously.Methods: Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression.Results: Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment.Conclusions: We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE. © 2010 Jin et al.; licensee BioMed Central Ltd.published_or_final_versio

Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all

Results of the worldwide, cross-sectional ASAS-PerSpA study

Objectives: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. Methods: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. Results: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%). Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). Conclusion: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.publishersversionpublishe

Multicenter validation of the value of BASFI and BASDAI in Chinese ankylosing spondylitis and undifferentiated spondyloarthropathy patients

The objectives of this study were to evaluate the reliability of Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis disease activity index (BASDAI) in Chinese ankylosing spondylitis (AS) and undifferentiated spondyloarthropathy (USpA) patients. 664 AS patients by the revised New York criteria for AS and 252 USpA patients by the European Spondyloarthropathy Study Group criteria were enrolled. BASDAI and BASFI questionnaires were translated into Chinese. Participants were required to fill in BASFI and BASDAI questionnaires again after 24 h. Moreover, BASDAI and BASFI were compared in AS patients receiving Enbrel or infliximab before and after treatment. For AS group, BASDAI ICC: 0.9502 (95% CI: 0.9330–0.9502, α = 0.9702), BASFI ICC: 0.9587 (95% CI: 0.9521–0.9645, α = 0.9789). For USpA group, BASDAI ICC: 0.9530 (95% CI: 0.9402–0.9632, α = 0.9760), BASFI ICC: 0.9900 (95% CI: 0.9871–0.9922, α = 0.9950). In the AS group, disease duration, occipital wall distance, modified Schober test, chest expansion, ESR, and CRP showed significant correlation with BASDAI and BASFI (all P < 0.01). In the USpA group, onset age, ESR, and CRP were significantly correlated with BASDAI (all P < 0.05), while modified Schober test, ESR, and CRP were significantly associated with BASFI (all P < 0.05). The change in BASDAI and BASFI via Enbrel or infliximab treatment showed a significant positive correlation (P < 0.01). The two instruments have good reliability and reference value regarding the evaluation of patient’s condition and anti-TNF-α treatment response

A cluster analysis in the worldwide ASAS-PerSpA study

Objective To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. Methods Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. Results The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist € s diagnosis as well as with the classification criteria was found. Conclusion These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations.publishersversionpublishe

Association between asymptomatic hyperuricemia and risk of arthritis, findings from a US National Survey 2007–2018

Background Arthritis is thought to be closely related to serum uric acid. The study aims to assess the association between asymptomatic hyperuricemia (AH) and arthritis.Methods A multistage, stratified cluster was used to conduct a cross-sectional study of adult US civilians aged≥20 years from the 2007–2018 National Health and Nutrition Examination Survey. Participants with hyperuricemia and without hyperuricemia prior to gout were included. A questionnaire was used to determine whether participants had arthritis and the type of arthritis. Logistic regression was used to investigate the association between hyperuricemia and arthritis.Result During the past 12 years, the percentage of participants with arthritis changed from 25.95% (22.53%–29.36%) to 25.53% (21.62%–29.44%). The prevalence of osteoarthritis (OA) increased from 8.70% (95% CI: 6.56% to 10.85%) to 12.44% (95% CI: 9.32% to 15.55%), the prevalence of AH changed from 16.35% (95% CI: 14.01% to 18.40%) to 16.39% (95% CI: 13.47% to 19.30%). Participants with AH were associated with onset of arthritis (OR=1.34, 95% CI: 1.07 to 1.69), but the association was muted after adjusting demographic and socioeconomic factors. For participants aged 40–49 years, AH is associated with incident arthritis (OR=1.96, 95% CI: 1.23 to 2.99) and the relationship remained after adjusting for education level, income to poverty ratio, body mass index, diabetes, hypertension and smoking (OR=2.00, 95% CI: 1.94 to 3.36). Compared with male, female participants with AH are more likely to develop arthritis, especially in OA (OR=1.35, 95% CI: 1.14 to 1.60).Conclusion Our data identified AH as the risk factor for incident arthritis, especially for OA, which might be exaggerated in aged population and female population