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Arthritis Research & Therapy Jul 2022Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are...
BACKGROUND
Male HLA-B27-positive radiographic-axial spondyloarthritis (r-axSpA) patients are prone to have severe spinal radiographic progression, but the underlying mechanisms are unclear. We recently showed that persistently elevated Lipocalin 2 (LCN2; L) reflects sacroiliac joint (SIJ) inflammation. LCN2 binds to MMP9. Concomitant elevation of L and LCN2-MMP9 (LM) was detected in many inflammatory diseases. We asked whether L and LM play similar roles in r-axSpA pathogenesis.
METHODS
We analyzed 190 axSpA patients (123 radiographic and 67 non-radiographic axSpA) who had no detectable circulating Oncostatin M, to avoid complications due to cross-talk between pathways. L and LM levels from a single blood sample of each patient were measured and were correlated with MRI and modified stoke AS (mSASS) scoring. Association of elevated L (L+) or concurrent L+ and elevated LM (LM+) patterns with B27 status and gender were assessed.
RESULTS
In L+LM+ axSpA patients, both L and LM levels correlated with MRI SPARCC SIJ scores, but only LM levels correlated with MRI Berlin Spine Scores, suggesting LM is a biomarker for both SIJ and spinal inflammation. Among patients with minimal spinal ankylosis (mSASSS < 10), 65% of male r-axSpA patients are L+LM+, while 30% and 64% of female patients are L+LM+ and L+, respectively, supporting the role of LM with disease progression. In B27+ L+LM+ male patients, both L and LM (but not CRP) levels correlate with mSASSS. B27 positivity and maleness have additive effects on spondylitis progression, suggesting concurrent high L and LM elevations are associated with B27+ male patients having more significant radiographic damage. L+ B27-negative male patients or L+ female patients are more likely to have milder disease.
CONCLUSION
L and LM are informative biomarkers for SIJ and spinal inflammation, as well as for ankylosing development in r-axSpA patients. Distinctive L+LM+ or L+ patterns not only could distinguish clinically aggressive vs milder course of disease, respectively, but also provide an explanation for B27-positive male patients being the most susceptible to severe ankylosis.
Topics: Ankylosis; Female; HLA-B27 Antigen; Humans; Inflammation; Lipocalin-2; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9; Sacroiliac Joint; Sacroiliitis; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 35804445
DOI: 10.1186/s13075-022-02854-2 -
Frontiers in Immunology 2023Axial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often...
OBJECTIVE
Axial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often diagnosed very late, which delays the optimal treatment period. Early diagnosis of axSpA, especially non-radiographic axSpA (nr-axSpA), remains a major challenge. This study aimed to investigate the diagnostic value of anti-Kaiso autoantibodies in axSpA and their correlation with clinical disease indicators.
METHODS
Two pooled serum samples (seven patients with nr-axSpA and seven healthy controls) were profiled using HuProt arrays to investigate the diagnostic value of autoantibodies in nr-axSpA. Levels of anti-Kaiso autoantibodies in patients with axSpA and controls were determined using the Meso Scale Discovery assay system. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of anti-Kaiso autoantibodies in axSpA. Pearson's correlation was used to assess the correlation between anti-Kaiso autoantibodies and clinical parameters.
RESULTS
Seven candidate autoantibodies were present in the serum of patients with nr-axSpA. The levels of anti-Kaiso autoantibodies were significantly higher in the nr-axSpA group than in the other groups. It can differentiate nr-axSpA from ankylosing spondylitis (AS), healthy controls, and rheumatoid arthritis. The level of early-stage AS among patients with nr-axSpA decreased when they progressed to the late stage. Of all patients with axSpA, serum anti-Kaiso autoantibody levels were positively correlated with the C-reactive protein level and the Bath Ankylosing Spondylitis Disease Activity Index score and negatively correlated with disease duration.
CONCLUSION
Anti-Kaiso autoantibody may be a valuable diagnostic biomarker for early-stage AS in the nr-axSpA period and may be a potential therapeutic target.
Topics: Humans; Spondylitis, Ankylosing; Spondylarthritis; Non-Radiographic Axial Spondyloarthritis; Inflammation; Arthritis, Rheumatoid
PubMed: 37063878
DOI: 10.3389/fimmu.2023.1156350 -
Arthritis and Rheumatism Mar 2008
Review
Topics: Female; Humans; Male; Sex Factors; Spondylitis, Ankylosing; Women's Health
PubMed: 18311755
DOI: 10.1002/art.23321 -
RMD Open Apr 2024Radiography and MRI of the sacroiliac joints (SIJ) are relevant for the diagnosis and classification of patients with axial spondyloarthritis (axSpA). This study aimed...
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.
Topics: Humans; Sacroiliac Joint; Spondylarthritis; Radiography; Spondylitis, Ankylosing; Axial Spondyloarthritis
PubMed: 38580341
DOI: 10.1136/rmdopen-2023-004044 -
Pediatric Rheumatology Online Journal Mar 2014To describe MRI and clinical findings in patients with juvenile idiopathic arthritis with cervical spine involvement at onset and follow-up under therapy.
BACKGROUND
To describe MRI and clinical findings in patients with juvenile idiopathic arthritis with cervical spine involvement at onset and follow-up under therapy.
METHODS
13 patients with signs of cervical spine involvement in juvenile idiopathic arthritis with a median disease duration of 1.7 years were included in the study. Clinical records and MR images were retrospectively analyzed according to symptoms and findings concerning the cervical spine.
RESULTS
At the onset of cervical spine involvement all patients showed limited range of motion, whereas only 5 of them complained of pain. In MR images joint hyperintensity, contrast enhancement, malalignment, ankylosis, erosion and narrowing of the spinal canal at cranio-cervical junction were found at 28, 32, 15, 2, 2 and 3 sites in 12 (93%), 13 (100%), 8 (62%), 2 (15%), 2 and 3 (20%) patients respectively. 3 of the 5 patients with pain (60%) showed ankylosis, erosions or narrowing of the spinal canal at cranio-cervical junction on MRI. At follow-up - after a median disease duration of cervical spine arthritis of 2.1 years and a variable duration of treatment with methotrexate (all patients) and biological agents (12 patients) - joint hyperintensity, enhancement and malalignment decreased to 15, 19 and 6 sites in 10 (77%), 11 (85%) and 3 (20%) patients respectively whereas ankylosis, erosion and narrowing of the spinal canal at cranio-cervical junction increased to 7, 6 and 4 sites in 3 (20%), 4 (31%) and 4 patients respectively. Pain was no longer reported, but 9 of 13 (69%) patients still had a limited range of motion with 6 of them (46%) showing skeletal changes on MRI.
CONCLUSIONS
This first MRI based follow-up study shows that cervical spine arthritis can follow a severe disease course in juvenile arthritis. While malalignments and inflammation sites decreased osseous changes with erosions, ankylosis, and narrowing of the spinal canal increased under treatment despite only minor subjective complaints. Therefore close MRI monitoring of these patients appears to be reasonable.
Topics: Adolescent; Ankylosis; Antirheumatic Agents; Arthritis, Juvenile; Biological Factors; Cervical Vertebrae; Child; Follow-Up Studies; Germany; Humans; Magnetic Resonance Imaging; Male; Methotrexate; Outcome Assessment, Health Care; Range of Motion, Articular; Spinal Diseases; Spinal Stenosis
PubMed: 24593886
DOI: 10.1186/1546-0096-12-9 -
Journal of Clinical Laboratory Analysis Dec 2022The objective of the study was to provide an overview of the existing evidence on non-genetic biomarkers for ankylosing spondylitis (AS).
OBJECTIVE
The objective of the study was to provide an overview of the existing evidence on non-genetic biomarkers for ankylosing spondylitis (AS).
METHODS
In this umbrella review, we searched PubMed and Web of Science from database inception to October 31, 2020. Systematic reviews and meta-analyses of observational studies investigating the associations between any non-genetic biomarkers and AS were included. We estimated summary standardized mean difference (SMD) along with 95% confidence interval (CI), I statistic, 95% prediction interval (PI), and assessed small-study effects and excess significance bias. The study was registered in PROSPERO with registration number of CRD42020218240.
RESULTS
A total of 1276 publications were identified, of which 21 articles covering 43 non-genetic biomarkers were eligible for inclusion. Evidence of 22 (51%) non-genetic biomarkers exhibited a nominally significant effect (p < 0.05) on AS, and 7 associations (14%) showed small-study effects. The associations of platelet count (SMD: 0.53, 95% CI: 0.36 to 0.71) and serum interleukin (IL)-23 levels (SMD = 2.03, 95% CI: 1.27 to 2.79) with AS presented highly suggestive evidence, while circulating IL-17 levels (SMD = 2.36, 95% CI: 1.71, 3.01) and Treg/PBMC ratio (SMD = -0.75, 95% CI: -1.06 to -0.44) presented suggestive evidence. However, these associations showed large or very large between-study heterogeneity, suggesting an indefinite direction for the effect when 95% PIs were considered.
CONCLUSION
No convincing evidence supported the existence of a non-genetic biomarker for AS. Some highly suggestive associations might be affected by bias, therefore, promising non-genetic biomarkers for AS remain limited at least based on the current evidence from observational studies.
Topics: Humans; Spondylitis, Ankylosing; Leukocytes, Mononuclear; Biomarkers
PubMed: 36347828
DOI: 10.1002/jcla.24759 -
Clinical and Experimental Rheumatology Sep 2022
Topics: Axial Spondyloarthritis; Humans; Severity of Illness Index; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 36129798
DOI: 10.55563/clinexprheumatol/lvvr1e -
Journal of Orthopaedic Surgery and... Jul 2022Ankylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone...
Ankylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone deacetylase 1 (HDAC1) is considered to be a key factor involved in inflammatory gene transduction, but its role in AS remains unclear. The purpose of this study was to explore the role and possible mechanism of HDAC1 in AS based on the Wnt-Smad pathway. Fibroblasts were isolated from hip synovial tissues of AS patients, adeno-associated virus (AAV) was used to regulate the expression of HDAC1, DKK-1 and SIS3 was used to inhibit Wnt and Smad, respectively. The expressions of Wnt-Smad pathway-related proteins were analyzed by WB, and the TRP ion channel proteins were analyzed by immunofluorescence and WB. The proliferation of AS fibroblasts was detected by CCK-8, the expression of inflammatory cytokines was detected by ELISA, and the effects of HDAC1 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that HDAC1 significantly affected the protein expressions of the Wnt-Smad pathway in AS fibroblasts, and Wnt inhibitor DKK-1 and Smad3 inhibitor SIS3 could significantly reverse the effect of HDAC1 on the Wnt-Smad pathway. In addition, HDAC1 significantly activated the TRP ion channel and promoted the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts. DKK-1 or SIS3 treatment significantly inhibit the effect of HDAC-1 on AS fibroblasts, suggesting that the Wnt-Smad pathway is involved in the regulation of AS by HDAC1. In conclusion, HDAC1 promotes the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts through the Wnt-Smad pathway.
Topics: Fibroblasts; Histone Deacetylase 1; Humans; Inflammation; Osteogenesis; Smad Proteins; Spondylitis, Ankylosing; Wnt Signaling Pathway
PubMed: 35794630
DOI: 10.1186/s13018-022-03224-z -
Pediatric Rheumatology Online Journal Sep 2020Temporomandibular joint (TMJ) arthritis and involvement is commonly seen in Juvenile Idiopathic Arthritis (JIA). Therapy includes conservative measures, but also...
BACKGROUND
Temporomandibular joint (TMJ) arthritis and involvement is commonly seen in Juvenile Idiopathic Arthritis (JIA). Therapy includes conservative measures, but also includes intraarticular corticosteroid injections (IASI) and systemic immunosuppressive therapy. Despite aggressive medical therapy, some patients develop arthritic changes and frank TMJ ankylosis that can result in persistent pain and limitation in range of motion (ROM). A surgical option is prosthetic TMJ replacement with concurrent correction of dentofacial deformities, which can be performed simultaneously. The objective of this study was to evaluate the outcomes of prosthetic TMJ replacement in a cohort of adolescent females with JIA and severe TMJ involvement.
METHODS
This is a retrospective case series that took place at one tertiary care center. Patients with a diagnosis of JIA who also underwent alloplastic TMJ replacement were identified through electronic medical record system (EMR) and reviewed. Chart review included analysis of all documents in the EMR, including demographic data, JIA history, surgical complications, ROM of TMJ measured by maximal incisal opening in millimeters (mm) and TMJ pain scores (4-point Likert scale: none, mild, moderate, severe) obtained pre- and postoperatively.
RESULTS
Five female patients, ages 15-17 year when TMJ replacement was performed, had nine total joints replaced with a post-operative follow-up period of 12-30 months. All patients had polyarticular, seronegative JIA and were treated with IASI and multiple immunosuppressive therapies without resolution of TMJ symptoms. One patient had bilateral TMJ ankylosis. Three of the five patients demonstrated significant dentofacial deformities, and all underwent simultaneous or staged orthognathic surgery. All patients had improvement in TMJ pain with most (80%) reporting no pain, and all had similar or improved ROM of their TMJ postoperatively. There was one delayed postoperative infection with Cutibacterium Acnes that presented 15 months after surgery and required removal and reimplantation of prosthesis.
CONCLUSION
The sequelae of TMJ arthritis and involvement from JIA in the adolescent population can be difficult to treat. Current medical therapy can be successful, however, in select cases that develop chronic changes in the TMJ despite extensive medical therapy, early results show that prosthetic joint replacement maybe a reasonable surgical option. With prosthetic joint replacement pain levels were reduced and range of motion was maintained or improved for all patients.
Topics: Adolescent; Ankylosis; Arthritis, Juvenile; Arthroplasty, Replacement; Female; Humans; Immunosuppressive Agents; Outcome and Process Assessment, Health Care; Pain Management; Postoperative Complications; Prosthesis Implantation; Prosthesis-Related Infections; Range of Motion, Articular; Recovery of Function; Reoperation; Temporomandibular Joint; Temporomandibular Joint Disorders
PubMed: 32887620
DOI: 10.1186/s12969-020-00453-6 -
Acta Orthopaedica Et Traumatologica... 2010Heterotopic ossification which may develop following elbow injuries or elbow surgery may result in complete loss of elbow functions. We evaluated the results of surgical...
OBJECTIVES
Heterotopic ossification which may develop following elbow injuries or elbow surgery may result in complete loss of elbow functions. We evaluated the results of surgical treatment for ankylosis of the elbow due to posttraumatic heterotopic ossification.
METHODS
The study included seven patients (6 males, 1 female; mean age 36 years; range 23 to 55 years) who developed heterotopic ossification and ankylosis of the elbow joint following surgical treatment of high-energy fractures in the circumference of the elbow. Two patients had comminuted olecranon fractures and elbow luxation, and five patients had comminuted intra-articular distal humeral fractures. Three patients had open fractures. Involvement was in the right elbow in two patients, and in the left elbow in five patients. One patient was monitored and treated in the intensive care unit for head trauma for 22 days. Initially, six patients were treated with plate osteosynthesis and one patient with tension band wiring. Foci of heterotopic ossification were detected on the radiographs taken after a mean of 24 days (range 20 to 32 days) following surgical treatment of fractures. The patients were followed-up with conventional radiography and scintigraphy for a mean of 11 months (range 7 to 15 months) before surgical treatment, during which functional loss in elbow joint movements deteriorated and ankylosis developed. All the patients had Hastings type IIIC ankylosis and poor Mayo elbow performance scores (mean score 50.7). A posterior incision was used in three patients, and a double-column incision was used in four patients. At surgery, the ulnar nerve and the lateral and medial collateral ligaments were preserved, and a posterolateral capsular release, removal of heterotopic ossification, purging of the olecranon fossa, and resection of the tip of the olecranon were performed. After completion of capsular release, cartilage pathologies were evaluated. Four patients were found to have no definite cartilage damage, whereas in three patients the joint cartilage was seriously damaged. At final controls, the patients were assessed with the Mayo elbow performance score. The mean follow-up period was 23.4 months (range 10 to 36 months).
RESULTS
In all cases, the range of motion and stability of the elbow joint were controlled and were found to be complete and stable at the end of the operation. At final controls, the Mayo elbow performance scores were good in three patients, moderate in one patient, and poor in three patients. All the patients with a poor elbow score had severe joint cartilage damage intraoperatively.
CONCLUSION
Patients who develop heterotopic ossification and ankylosis of the elbow following trauma or elbow surgery may benefit from removal of heterotopic ossification foci and elbow relaxation procedures provided that there is not severe damage to the articular cartilage.
Topics: Adult; Ankylosis; Elbow; Elbow Joint; Female; Humans; Male; Middle Aged; Ossification, Heterotopic; Radiography; Range of Motion, Articular; Treatment Outcome; Young Adult; Elbow Injuries
PubMed: 21088461
DOI: 10.3944/AOTT.2010.2441