MRI Changes of the Symphysis Pubis in Patients With Axial Spondyloarthritis and Association With Clinical Factors.

OBJECTIVE: This study aimed to evaluate the magnetic resonance imaging (MRI) changes of the symphysis pubis in patients with axial spondyloarthritis (ax-SpA) and to assess its association with clinical factors. METHODS: A retrospective analysis of 172 patients with ax-SpA was performed to assess the presence of active inflammatory and structural changes of the symphysis pubis on MRI scans, and their association with clinical factors and the SPARCC (Spondyloarthritis Research Consortium of Canada) scoring of the sacroiliac joint were evaluated. RESULTS: The proportions of active inflammation and structural changes of the symphysis pubis were 69/172 (40.1%) and 54/172 (31.4%), respectively. When comparing the active inflammation and no-active inflammation symphysis pubis groups, the former had higher level C-reactive protein, higher erythrocyte sedimentation rate, and younger median age of patients. Moreover, no significant correlation was noted between the active inflammation of the symphysis pubis and SPARCC score of the sacroiliac joint. When comparing the normal and abnormal symphysis pubis groups, the latter had longer symptom duration. CONCLUSIONS: The MRI changes of the symphysis pubis were seen in 55.2% of the patients with ax-SpA and were associated with C-reactive protein, erythrocyte sedimentation rate, and symptom duration.

CD27-CD38lowCD21low B-Cells Are Increased in Axial Spondyloarthritis.

B-cells have received little attention in axial spondyloarthritis (axSpA) and for this reason their role in pathogenesis remains unclear. However, there are indications that B-cells may be involved in the disease process. Our objective was to obtain insights into the composition of the peripheral B-cell compartment of axSpA patients compared to healthy donors (HD) and patients with primary Sjögren's syndrome (pSS), a typical B-cell-associated autoimmune disease. Special emphasis was given to CD27-negative B-cells expressing low levels of CD21 (CD21low B-cells), since this subset is implicated in autoimmune diseases with strong involvement of B-cells. Transitional B-cells (CD38hi) were excluded from the analysis of the CD27-CD21low B-cell compartment. This study included 45 axSpA patients, 20 pSS patients and 30 HDs. Intriguingly, compared to HDs the frequency of CD27-CD38lowCD21low B-cells was significantly elevated in both axSpA and pSS patients (P<0.0001 for both comparisons). The frequency of CD27-CD38lowCD21low B-cells expressing the activation-induced immune markers T-bet and CD11c was decreased in axSpA patients compared to HDs. A higher proportion of CD27-CD38lowCD21low B-cells expressed the chemokine receptor CXCR3 in axSpA compared to HDs, suggestive for active involvement of these cells in an inflammatory process. The frequency of CD27-CD38lowCD21low B-cells in axSpA patients correlated positively with age and erythrocyte sedimentation rate. Furthermore, axSpA patients with extra-skeletal manifestations (ESM) showed increased frequencies of CD27-CD38lowCD21low B-cells compared to patients without ESM. In conclusion, our findings are suggestive of active B-cell involvement in the pathogenesis of axSpA, against prevailing dogma.

Clonal expansion of large granular lymphocytes in patients with spondyloarthritis and psoriatic arthritis treated with TNFα inhibitors.

To determine the prevalence of clonal T-large granular lymphocyte (T-LGL) cells in patients with spondyloarthritis (SpA) and psoriatic arthritis (PsA) and to define possible risk factors for this condition. We present a cross-sectional analysis with retrospective and prospective aspects. 115 SpA patients, 48 PsA patients and 51 controls were recruited between December 28, 2017 and January 23, 2019. Flow cytometry (FACS) was performed to screen for aberrant T-LGL cells. Molecular analysis was then employed to confirm the diagnosis in patients with suggestive FACS findings. Patients with clonal T-LGL populations were followed prospectively by FACS analysis. Electronic patient files were retrospectively analyzed to determine risk factors. Median age was 49 years for SpA, 55.5 years for PsA, and 54 years for controls. Median disease duration of SpA and PsA was 15 years and 11 years, respectively. 79.8% of patients had received biologics at some point, 75.5% had ever received tumor necrosis factor (TNF) inhibitors. 59.5% were treated with TNF inhibitors at the time of study inclusion. We identified clonal T-LGL expansions in 13 individuals equaling a prevalence of 6% (13/214). T-LGL patients were taking TNF inhibitors more frequently at the time of study inclusion (p = 0.022) and were more likely to have ever been treated with TNF inhibition (p = 0.046). Clonal T-LGL expansions can be detected in patients with SpA, PsA and also in healthy controls. Confirming earlier results, exposure to TNFα-blocking agents appears to increase the risk of developing clonal expansions of T-LGL cells.

Associations of ultrasound-based inflammation patterns with peripheral innate lymphoid cell populations, serum cytokines/chemokines, and treatment response to methotrexate in rheumatoid arthritis and spondyloarthritis.

OBJECTIVES: We aimed to explore the associations of musculoskeletal inflammation patterns with peripheral blood innate lymphoid cell (ILC) populations, serum cytokines/chemokines, and treatment response to methotrexate in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: We enrolled 100 patients with either RA or SpA and performed ultrasound to evaluate power Doppler signals for synovitis (52 joint regions), tenosynovitis (20 tendons), and enthesitis (44 sites). We performed clustering analysis using unsupervised random forest based on the multi-axis ultrasound information and classified the patients into groups. We identified and counted ILC1-3 populations in the peripheral blood by flow cytometry and also measured the serum levels of 20 cytokines/chemokines. We also determined ACR20 response at 3 months in 38 patients who began treatment with methotrexate after study assessment. RESULTS: Synovitis was more prevalent and severe in RA than in SpA, whereas tenosynovitis and enthesitis were comparable between RA and SpA. Patients were classified into two groups which represented synovitis-dominant and synovitis-nondominant inflammation patterns. While peripheral ILC counts were not significantly different between RA and SpA, they were significantly higher in the synovitis-nondominant group than in the synovitis-dominant group (ILC1-3: p = 0.0007, p = 0.0061, and p = 0.0002, respectively). On the other hand, clustering of patients based on serum cytokines/chemokines did not clearly correspond either to clinical diagnoses or to synovitis-dominant/nondominant patterns. The synovitis-dominant pattern was the most significant factor that predicted clinical response to methotrexate (p = 0.0065). CONCLUSIONS: Musculoskeletal inflammation patterns determined by ultrasound are associated with peripheral ILC counts and could predict treatment response to methotrexate.

Axial and peripheral spondyloarthritis triggered by sars-cov-2 infection: a report of two cases.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can show musculoskeletal symptoms such as peripheral arthritis. In rare cases, peripheral arthritis can develop after the resolution of SARS-CoV-2. We present two cases of spondyloarthritis induced by SARS-CoV-2; one case with axial and peripheral spondyloarthritis and the other with peripheral spondyloarthritis. Both cases refer to Lebanese patients who were HLA-B27 positive. These two cases highlight the possible predisposition of HLA-B27 positive patients to the development of spondyloarthritis symptoms triggered by SARS-CoV-2.

Down-Regulation of Dkk-1 in Platelets of Patients With Axial Spondyloarthritis.

OBJECTIVE: Axial spondyloarthritis (SpA) is a chronic autoinflammatory disease with new bone formation, which is controlled by Wnt/ß-catenin signaling. Dkk-1 is an inhibitor of the Wnt pathway, and in humans, platelets represent a major source of Dkk-1. This study was undertaken to investigate whether levels of Dkk-1 in serum and platelet expression of DKK1 messenger RNA (mRNA) and Dkk-1 protein are affected in patients with axial SpA compared to healthy controls. METHODS: Forty-one patients with axial SpA and 35 healthy controls were enrolled in the study. Total serum Dkk-1 levels in all patients and healthy controls were measured by quantitative enzyme-linked immunosorbent assay. Platelet DKK1 mRNA was analyzed by quantitative reverse transcriptase-polymerase chain reaction in 20 patients with axial SpA and 20 controls, and Dkk-1 protein levels were measured by immunoblotting in 20 patients with axial SpA and 18 controls. RESULTS: We found a lower concentration of Dkk-1 in the serum from patients with axial SpA compared to the serum from healthy controls (P < 0.0001). Furthermore, the expression of Dkk-1 was significantly reduced both at the transcriptional level (P < 0.04) and at the protein level (P < 0.007) in platelets isolated from the blood of patients with axial SpA. CONCLUSION: Our preliminary observations suggest that dysfunction of the megakaryocyte/platelet axis might be responsible for reduced serum Dkk-1 levels in patients with axial SpA. Dkk-1 is down-regulated in the platelets of patients with axial SpA, a mechanism that might play a role in new bone formation.

Antibodies to malondialdehyde-acetaldehyde modified low-density lipoprotein in patients with newly diagnosed inflammatory joint disease.

Objective:To assess antibodies to malondialdehyde-acetaldehyde-modified low-density lipoprotein (MAA-LDL) in patients with newly diagnosed inflammatory joint disease.Method: Patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and undifferentiated arthritis (UA), participating in the Northern Savo 2010 Study, were evaluated for metabolic syndrome (MetS), metabolic and inflammatory markers, antibodies to MAA-LDL, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis.Results: Among 135 newly diagnosed untreated patients, of whom 53 (39%) were diagnosed to have RA, 44 (33%) SpA, and 38 (28%) UA, 49%, 30%, and 47%, respectively, had MetS. After adjusting for age and gender, anti-MAA-LDL immunoglobulin (Ig)A (p = 0.009), IgG (p = 0.031), and IgM (p = 0.001) levels differed between the diagnostic categories, but not in patients with MetS present or absent. All antibody classes to MAA-LDL correlated with erythrocyte sedimentation rate (ESR), and IgA and IgG antibodies with high-sensitivity C-reactive protein (hs-CRP). IgA antibodies to MAA-LDL correlated with rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), fasting plasma glucose, IgA antibodies to A. actinomycetemcomitans, and in IgA and IgG antibodies to P. gingivalis.Conclusion: Among various arthritis groups, antibodies to MAA-LDL were most common in RA. Antibodies to modified lipoproteins were associated with inflammation measured by ESR and hs-CRP. IgA antibodies to MAA-LDL correlated with age, antibodies to periodontal bacteria, RF, ACPA, and fasting glucose. Associations between antibodies to MAA-LDL and antibodies to periodontal bacteria, RA-associated antibodies, inflammatory parameters, and plasma glucose already reflect cardiovascular burden in inflammatory joint diseases at diagnosis.

Antibodies against carbamylated proteins: prevalence and associated disease characteristics in Belgian patients with rheumatoid arthritis or other rheumatic diseases.

Objectives: Anti-carbamylated protein antibodies (anti-CarP) are reported to be associated with increased disease activity and with more severe joint damage in rheumatoid arthritis (RA) patients. The present study investigated the presence of anti-CarP in various rheumatic diseases, and their specific clinical significance in RA, in Belgian rheumatology patients.Method: We tested sera from 254 RA patients, 56 healthy controls, and 153 patients with different rheumatic conditions: juvenile idiopathic arthritis (JIA), axial spondyloarthritis, systemic sclerosis, and Sjögren's syndrome (SS). An in-house enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies against carbamylated foetal calf serum.Results: Anti-CarP were detected in 88 RA patients (34.6%), of whom 82% were also positive for anti-citrullinated protein antibodies (ACPAs) and 81% were also rheumatoid factor (RF) positive. Of note, 11 anti-CarP single-positive patients were detected (4.3%). The previously reported association with joint erosions was not detected. However, in ACPA- and RF-negative RA patients, the presence of anti-CarP was associated with higher disease activity and disability. Fifteen per cent of JIA patients and 30% of SS patients also tested positive for anti-CarP and their antibody levels did not differ significantly from those of anti-CarP-positive RA patients. Anti-CarP levels were, however, significantly higher in ACPA- or RF-positive patients.Conclusion: Anti-CarP antibodies were detected in the sera of a cohort of Belgian RA patients. Moreover, they were also detected in primary SS patients and in JIA patients. In the seronegative subset of RA patients, anti-CarP antibodies showed prognostic value.

Prevalence of anti-cyclic citrullinated peptide antibodies in patients with spondyloarthritis: A retrospective study.

OBJECTIVES: Anti-cyclic citrullinated peptide (CCP) antibodies are frequently detected in the sera of patients with rheumatoid arthritis (RA). However, recent studies have revealed a potentially high prevalence rate of these antibodies in patients with other rheumatic disorders, causing confusion while diagnosing RA. Therefore, this study aimed to evaluate the positive rate of anti-CCP antibodies in other chronic arthritis diseases focusing on patients with spondyloarthritis (SpA). METHODS: A total of 109 patients who were diagnosed with SpA at Yukioka Hospital from 1993 to 2018 were included in this retrospective analysis, including patients with ankylosing spondylitis (AS); psoriatic arthritis (PsA); synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (SAPHO); undifferentiated spondyloarthritis (uSpA); reactive arthritis (ReA); and inflammatory bowel disease-associated SpA (IBD). RESULTS: Overall, 15.3% (16/109) of patients with SpA were positive for anti-CCP antibodies, including 2.3% (1/43) in AS, 23.1% (3/13) in SAPHO, 35.0% (7/20) in PsA, 14.8% (4/27) in uSpA, 0% (0/3) in ReA, and 33.3% (1/3) in IBD. CONCLUSION: PsA patients have a significantly higher prevalence rate of positive anti-CCP antibodies among SpA patients, and the positive rates in SAPHO and uSpA were also high. These findings provide insight into the heterogeneity of SpA with relevance for RA differential diagnosis.

Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease-associated spondyloarthritis.

OBJECTIVES: Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients. METHODS: Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line. RESULTS: Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells. CONCLUSION: SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.

Changes in bone formation regulator biomarkers in early axial spondyloarthritis.

OBJECTIVE: The hallmark of advanced axial SpA (axSpA) is spine ankylosis due to excessive ectopic bone formation. This prospective study aimed to describe the changes in serum levels of different regulators [sclerostin, dickkopf-1 (DKK-1)] and markers of bone formation [bone morphogenetic protein 7 (BMP-7)] over 5 years in early axSpA patients and to assess determinants of such changes. METHODS: The DEvenir des Spondyloarthropathies Indifférenciées Récentes cohort is a prospective, multicentre French study of 708 patients with early (>3 months-<3 years) inflammatory back pain suggestive of axSpA. Serum levels of BMP-7, sclerostin and DKK-1 were assessed at baseline and after 2 and 5 years. Changes in bone formation regulators over time were analysed using mixed linear models. RESULTS: Serum BMP-7 significantly increased over time, with a median relative change of 223.7% [interquartile range (IQR) 0-10 700 (0.17 pg/ml/month), P < 0.001]. Serum sclerostin significantly increased over time, with a median relative change of 14.8% [IQR -7.9-41.4% (0.001 ng/ml/month), P < 0.001]. Serum DKK-1 did not significantly change over time. Serum BMP-7 increased over time in active disease (Ankylosing Spondylitis Disease Activity Score with CRP ≥1.3, P = 0.01), but the increase was less pronounced with TNF inhibitor (TNFi) use (P < 0.001). No determinant was associated with serum sclerostin change. CONCLUSION: Serum BMP-7 change over 5 years was related with inflammation; it was increased in active disease, but the increase was low with TNFi use. Serum sclerostin levels significantly increased over time, but to a lesser degree than for serum BMP-7. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, NCT01648907.

Doctor's aptitude for switching from innovator etanercept to biosimilar etanercept in inflammatory rheumatic diseases: experience from a single French rheumatology tertiary care center.

OBJECTIVES: To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting METHODS: We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. RESULTS: Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p < 0.001). After a 6-month follow-up, bETN retention rate was 83% (95% CI: 0.76-0.92). The first cause of bETN discontinuation was inefficacy (50%). On multivariate analysis, no factor was independently associated with a bETN switch or discontinuation. Drug trough levels did not significantly differ by discontinuation or continuation of bETN. No patient showed anti-drug antibodies. CONCLUSION: The probability of switching from iETN to bETN was likely related to physician characteristics.

Proprotein convertase subtilisin/kexin type 9 in the dyslipidaemia of patients with axial spondyloarthritis is related to disease activity.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism and has been linked to cardiovascular (CV) risk. The purpose of the present study was to examine whether PCSK9 levels are related to abnormalities in the lipid profile and the development of atherosclerosis that occurs in patients with axial SpA (axSpA). METHODS: We performed a cross-sectional study that encompassed 545 individuals; 299 patients with axSpA and 246 statin use-matched controls. PCSK9 and standard lipid profiles were analysed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in patients. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the influence of PCSK9 on axSpA-related dyslipidaemia and subclinical carotid atherosclerosis. RESULTS: Total cholesterol, high-density lipoprotein and low density lipoprotein cholesterol, lipoprotein (a) and apolipoprotein A1 were significantly lower in axSpA patients than controls. PCSK9 serum levels [ß coefficient -44 ng/dl (95% CI -60, -27), P = 0.000] were also downregulated in axSpA patients after fully multivariable adjustment. ASDAS-CRP was found to be independently and significantly related to PCSK9 [ß coefficient 10 ng/dl (95% CI 1, 18), P = 0.023] after analysing fully adjusted models that took age, sex and the rest of the lipid profile molecules into account. Whereas patients taking prednisone showed higher serum levels of PCSK9 [55 ng/ml (95% CI 24, 8), P = 0.001], those under anti-TNF-α therapies exhibited lower levels [ß coefficient -26 ng/ml (95% CI -43, -9], P = 0.003]. CONCLUSION: PCSK9 is downregulated in patients with axSpA. Disease activity is positive and significantly related to PSCK9. Anti-TNF-therapy yields a reduction in PCSK9 serum levels.

Is seronegative rheumatoid arthritis true rheumatoid arthritis? A nationwide cohort study.

OBJECTIVES: The classification of seronegative arthritides can be challenging. Our aim was to examine the incidence of SpA diagnosis among patients initially diagnosed as seronegative RA. METHODS: Using nationwide Finnish registers from social insurance institutions, we identified all adult patients who were diagnosed with incident seronegative RA [International Classification of Diseases (ICD)-10 code M06] from 1 January 2000 to 31 December 2014. The patients whose diagnoses subsequently changed to the ICD-10 codes of SpA (M07, M45, M46, K50 and K51) were identified in the national care register, until 31 December 2016. RESULTS: A total of 9784 adult seronegative RA patients were identified. Of these, 564 patients had their diagnosis subsequently changed to SpA: 275 (48.7%) patients with PsA, 245 (43.4%) patients with axial SpA and 44 (7.8%) patients with diagnoses related to IBD. The cumulative incidence of SpA diagnoses in 15 years was 10.4% (95% CI 8.9, 12.1) and 8.1% (95% CI 7.1, 9.3) in men and women, respectively. CONCLUSION: This study calls for vigilance in seronegative RA patients, especially those with more atypical presentations, since the diagnosis could change. The possibility of SpA diagnosis should be considered and specifically looked for, as this could impact on management and response to treatment.

Anti-CD74 IgA autoantibodies in radiographic axial spondyloarthritis: a longitudinal Swedish study.

OBJECTIVES: Antibodies against anti-CD74 are related to axial spondyloarthritis (axSpA). The objectives were (i) to study IgA anti-CD74 in radiographic (r)-axSpA patients in the Backbone cohort and to calculate the sensitivity and specificity of anti-CD74, (ii) to study the fluctuation of IgA anti-CD74 levels in prospectively collected samples, and (iii) to explore the relation between IgA anti-CD74 and radiographic spinal changes. METHODS: IgA anti-CD74 was analysed by ELISA in 155 patients with r-axSpA and age- and sex-matched controls. BASDAI, ASDAS, BASFI and BASMI were assessed and spinal radiographs were scored for r-axSpA-related changes with mSASSS. Previously donated samples, before inclusion in the Backbone study, were identified in the Medical Biobank of Northern Sweden. RESULTS: A total of 155 patients comprising 69% men and 31% women, age [mean (s.d.)] 55.5 (11.4) years and 152 (98.1%) HLA-B27 positive, were included. The plasma level of IgA anti-CD74 was significantly higher in the patients [median (interquartile range), 12.9 (7.9-17.9) U/ml] compared with controls [10.9 (7.2-14.6) U/ml, P = 0.003]. IgA anti-CD74 was above the cut-off level of 20 U/ml in 36/155 (23.2%) patients and in 15/151 (9.9%) controls (P = 0.002). Multivariable logistic regression analyses revealed ≥1 syndesmophyte associated with IgA anti-CD74 (odds ratio 5.64; 95% CI: 1.02, 35.58; P = 0.048) adjusted for hsCRP, smoking, BMI, sex and age. No distinct pattern of IgA anti-CD74 over time was revealed. CONCLUSION: Plasma levels of IgA anti-CD74 were increased in r-axSpA and independently associated with radiographic spinal changes, which suggests that IgA anti-CD74 could play a role in the pathogenies of r-axSpA.

Expression and clinical significance of circular RNA hsa_circ_0079787 in the peripheral blood of patients with axial spondyloarthritis.

Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease involving the axial skeleton. Recent evidence suggested that certain circular RNAs (circRNAs) have a crucial role in rheumatic diseases. However, the functions of circRNAs in AxSpA have remained largely elusive. The present study identified the utility of the circRNA Homo sapiens (hsa)_circ_0079787 as a potential biomarker for AxSpA. A total of 5 circRNAs (hsa_circ_0002715, hsa_circ_0001947, hsa_circ_0079787, hsa_circ_0000367 and hsa_circ_0035197) were determined in the peripheral blood of 46 patients with AxSpA, 46 patients with systemic lupus erythematosus (SLE) and 25 healthy controls (HC) by reverse transcription­quantitative PCR analysis. The detailed clinical history of each patient was recorded and the correlations between these circRNAs and clinical characteristics were analyzed. Furthermore, receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of hsa_circ_0079787 and other factors for AxSpA. Of the 5 selected circRNAs, the expression of hsa_circ_0079787 was indicated to be significantly reduced in the peripheral blood of patients with AxSpA as compared with the levels in HCs and patients with SLE. The peripheral blood levels of hsa_circ_0079787 in patients with AxSpA were negatively correlated with the Bath Ankylosing Spondylitis Disease Activity Index and positively correlated with the platelet count (PLT) and the lymphocyte­to­monocyte ratio. In addition, the expression of peripheral blood hsa_circ_0079787 in male patients with AxSpA was negatively correlated with the mean platelet volume (MPV) and positively correlated with the plateletcrit (PCT). ROC curve analysis suggested that hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT had a significant diagnostic value for AxSpA. hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT was also able to differentiate between patients with AxSpA and those with SLE. In conclusion, peripheral­blood hsa_circ_0079787 and the combination of hsa_circ_0079787­PLT­MPV­PCT may provide improved diagnostic accuracy for AxSpA. In addition, the levels of hsa_circ_0079787 in the peripheral blood were correlated with disease activity and severity of AxSpA.

Interleukin-17A biomarker as a predictor for detection of early axial spondyloarthritis changes in patients with psoriasis.

AIM: Although the pathogenic mechanisms of psoriatic arthritis (PsA) are not completely clarified, evidence suggests that interleukin 17A (IL-17A)-mediated immune responses play a pivotal role in the disease. This is best underscored by the important clinical effectiveness of IL-17A inhibitors in psoriasis treatment. We aim to investigate the predictive value of IL-17A in detecting the early axial spondyloarthropic (SpA) changes in psoriatic patients. METHODS: The study enrolled 100 patients with psoriasis, classified into group 1, included 62 patients with only psoriatic skin lesions (Ps), and group 2 included 38 patients with PsA, and 100 age and gender matched healthy volunteers. All participants were subjected to general and local clinical examination, laboratory assessment including IL-17A in the serum by means of enzyme-linked immunosorbent assay, and axial joint radiological assessment. RESULTS: Our study included 60 males (60%) and 40 females (40%).The positive radiological findings of early axial SpA changes were found among 30.6% of the Ps group and among 84.2% of the PsA group. There were significant differences between patients with positive magnetic resonance imaging (MRI) findings of early axial SpA and patients with negative MRI findings in both groups regarding IL-17A levels. There was a significant association between IL-17A level and early axial SpA changes in psoriatic patients with a clear cutoff point (222.5). CONCLUSION: Our study can imply that IL-17A is a valuable, useful and low-cost biomarker in detecting early axial SpA changes in asymptomatic and nonradiographic axial SpA (nr-axial SpA) psoriatic patients that helps early management and prevent progressive axial involvement and disabilities.

Complement activation in human autoimmune diseases and mouse models; employing a sandwich immunoassay specific for C3dg.

In human autoimmune diseases, low plasma levels of complement factors C3 and C4 are commonly used as a proxy for complement activation. The measurements of C3 and C4 concentrations (the result of synthesis and consumption) however, show low sensitivity in patient follow-up. We find that the estimation of the C3dg fragment released during complement activation is a better parameter for complement activation. Available techniques for measuring the activation fragment C3dg, e.g. immune-electrophoresis or involving PEG-precipitation, are time-consuming and difficult to standardize. Here we examine the specificity and use of an antibody with mono-specificity for a neoepitope at the N-terminus of C3dg, which is only exposed after cleavage of C3. We present a stable, reproducible, and easy-to-use, time-resolved immunoassay with specificity for C3dg that can be used to directly evaluate ongoing complement activation. We demonstrate that the assay can be applied to clinical samples with a high specificity (95%) and a positive likelihood ratio of 10. It can also differentiate the complement related disease Systemic Lupus Erythematosus from controls and other immune-mediatedimmune mediated diseases like Rheumatoid Arthritis (86% specificity) and Spondyloarthritis (91% specificity). Further, we establish how the assay may also be used for experimental research in in vivo mouse models.

Bone turnover biomarkers, disease activity, and MRI changes of sacroiliac joints in patients with spondyloarthritis.

The lack of valid biomarkers in patients with spondyloarthritis (SpA) requires searching for additional options to increase sacroiliac joint (SIJ) evaluation effectiveness. We assessed the serum levels of bone turnover markers and their relationships with active and chronic changes in SIJs using magnetic resonance imaging (MRI), indices, and laboratory parameters of disease activity in SpA patients. 102 patients with SpA and 15 healthy subjects were included. Testing of serum levels of transforming growth factor-beta (TGF-ß1), Wnt3, sclerostin, and Dickkopf-1 (Dkk-1) was conducted. Active inflammatory lesions in SIJs were evaluated using Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ score, and chronic changes using the Danish scoring method. Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Ankylosing Spondylitis Disease Activity Scores with CRP, and ESR were used to assess disease activity. Serum levels of Dkk-1, TGF-ß1, and sclerostin were significantly lower in SpA patients compared to healthy controls. The serum levels of Dkk-1 positively correlated with CRP. Dkk-1 had a significant negative correlation with Danish score. The sclerostin serum level had a weak negative correlation with the active inflammatory MRI SIJ lesions. There were positive correlations between TGF-ß1 and sclerostin with Dkk-1, and negative correlation between Wnt3 and sclerostin. Dkk-1 positively correlated with CRP and negatively with chronic SIJ changes by Danish score. Sclerostin negatively correlated with the active SIJ lesions by SPARCC. This suggests that Dkk-1 and sclerostin are the most promising candidates to reveal inflammation and bone turnover in patients with SpA.

Calprotectin in spondyloarthritis: A systematic review and meta-analysis.

OBJECTIVE: There is still an unmet need for a simple and reliable biomarker for diagnosis and disease activity of spondyloarthritis. Recent studies indicated that calprotectin could act as a biomarker for spondyloarthritis. Therefore, this systematic review and meta-analysis aims to evaluate the levels of serum and fecal calprotectin in spondyloarthritis and the associations with disease activity. METHODS: PubMed, Web of Science and Cochrane Library were comprehensively searched from inception to July 1st, 2019. The pooled standard mean differences (SMDs) were used to estimate the differences of the levels of serum and fecal calprotectin between spondyloarthritis patients and controls. Spearman correlation coefficients were used for evaluating the associations between the levels of serum and fecal calprotectin and disease activity of spondyloarthritis patients. The use of fixed-effect or random-effects model depended on heterogeneity. RESULTS: Among 257 searched studies, 20 studies were finally included for analysis. Serum and fecal calprotectin were both significantly increased in spondyloarthritis patients compared to matched controls (SMD = 1.49, 95% CI = 0.91 to 2.08; SMD = 2.29, 95% CI = 0.25 to 4.33). The pooled correlation coefficients between serum or fecal calprotectin and CRP, ESR, BASDAI and BASFI were 0.353, 0.228, 0.225, 0.131 and 0.185, 0.163, 0.280, 0.196 respectively. CONCLUSION: Our study indicated that serum and fecal calprotectin were significantly increased in spondyloarthritis patients, and associated with disease activity. Serum and fecal calprotectin were potential biomarkers for the diagnosis and disease activity of spondyloarthritis.