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1.
Rheumatology (Oxford) ; 61(12): 4722-4730, 2022 11 28.
Article in English | MEDLINE | ID: mdl-35302592

ABSTRACT

OBJECTIVES: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion. METHODS: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects. RESULTS: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses. CONCLUSIONS: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA.


Subject(s)
Axial Spondyloarthritis , Spondylarthropathies , Spondylitis, Ankylosing , Zygapophyseal Joint , Humans , Male , Middle Aged , Female , Zygapophyseal Joint/diagnostic imaging , Spondylitis, Ankylosing/pathology , Spondylarthropathies/pathology , Spine/pathology , Tomography, X-Ray Computed , Inflammation/pathology
2.
Clin Radiol ; 77(10): e783-e788, 2022 10.
Article in English | MEDLINE | ID: mdl-35940928

ABSTRACT

AIM: To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy. MATERIALS AND METHODS: Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient. RESULTS: The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k = 0.747 and 0.712), and moderate for opposed-phase images (k = 0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively. CONCLUSION: The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.


Subject(s)
Spondylarthritis , Spondylarthropathies , Edema/diagnostic imaging , Edema/pathology , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Spondylarthropathies/complications , Spondylarthropathies/diagnostic imaging , Spondylarthropathies/pathology
3.
J Comput Assist Tomogr ; 46(2): 190-196, 2022.
Article in English | MEDLINE | ID: mdl-35297576

ABSTRACT

AIM: To test the diagnostic efficacy of a multiparametric rheumatology lumbosacral magnetic resonance (MR) imaging protocol in detection and characterization of axial spondylarthritis (SpA) and compare it with serology and clinical findings. METHODS: A consecutive series of multiparametric rheumatology lumbosacral MR imaging examinations performed on 3T MR scanner. Three-dimensional inversion recovery turbo spin echo, precontrast and postcontrast fat-suppressed T1-weighted images, as well as diffusion-weighted images were used to detect active erosions and enthesitis using established criteria. Pearson χ2 was used for categorical variables. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were measured for magnetic resonance imaging (MRI) and serology, based on the final diagnosis from rheumatologists. An alpha error below 0.05 was considered statistically significant. RESULTS: The final study sample included 130 consecutive patients (80 women and 50 men; mean ± SD 44 ± 13 and 45 ± 14 years, respectively). Seventy-eight subjects were diagnosed with axial SpA and 52 with non-SpA arthropathy. In the non-SpA group, 27 patients were diagnosed with osteoarthritis, 6 had unremarkable imaging, whereas 19 were considered as clinically undetermined. There was positive correlation between positive MRI results and SpA diagnosis (P < 0.00001). No correlation existed between positive serology alone and SpA diagnosis (P = 0.0634). Although MRI and serology proved equally sensitive in detecting SpA, the specificity and overall accuracy of MRI were significantly higher. Inflammatory activity was detected in 45 (57.7%) cases, in the pelvic enthesis in 29 (37.2%) cases, in the lumbosacral spine in 16 (20.5%) cases, in the hip joints in 15 (19.2%) cases, and in the pubic symphysis in 5 (6.4%). Inactive sacral disease was seen in 7 of 35 enthesitis patients (20.0%), and in 2 SpA cases, there were no sacral lesions. CONCLUSIONS: The results suggest that in patients with suspected SpA, MRI should not be limited to the sacroiliac joints, but also include enthesitis sites and other joints of the axial skeleton. The multiparametric rheumatology protocol increases the efficacy of MRI in detecting enthesitis and joint inflammatory disease, thereby offering additional information to the clinician and assisting in the early diagnosis/detecting disease activity.


Subject(s)
Rheumatology , Spondylarthritis , Spondylarthropathies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Sacroiliac Joint/diagnostic imaging , Spondylarthritis/complications , Spondylarthritis/diagnostic imaging , Spondylarthropathies/diagnostic imaging , Spondylarthropathies/pathology
4.
Rheumatology (Oxford) ; 60(3): 1465-1473, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33011808

ABSTRACT

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.


Subject(s)
Arthritis, Psoriatic/diagnosis , Aged , Arthritis, Psoriatic/pathology , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Reproducibility of Results , Spondylarthropathies/diagnosis , Spondylarthropathies/pathology , Surveys and Questionnaires
5.
Clin Radiol ; 74(5): 409.e1-409.e6, 2019 05.
Article in English | MEDLINE | ID: mdl-30791997

ABSTRACT

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.


Subject(s)
Sacroiliac Joint/pathology , Spine/pathology , Spondylarthropathies/pathology , Adolescent , Adult , Aged , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Retrospective Studies , Unnecessary Procedures , Young Adult
6.
J Autoimmun ; 94: 70-82, 2018 11.
Article in English | MEDLINE | ID: mdl-30064915

ABSTRACT

Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying the pathogenesis of diseases, especially those having an autoimmune background such as spondyloarthopaties (SpA). Reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to molecular genetic screening. Here, we focused our investigation in a medieval necropolis in the Basque Country (13th-15th century, N = 163), which presents a high frequency of joint pathologies through two approaches: on the one hand, the analysis of joint manifestations for the differential diagnosis of the SpA and, on the other hand, the determination of the alleles of the HLA-B gene. The morphological analysis allowed determining that 30% of the individuals had rheumatic bone manifestations, with SpA being the most frequent (45%). The genetic analysis of individuals with and without pathologies, based on the study of the HLA-B gene, allowed finding 17 alleles for this gene, with HLA-B40, HLA-B27 and HLA-B35 being the most frequent. Although these alleles have been traditionally described as genetic markers associated to the development of SpA, in this study they were also found in individuals with other rheumatic diseases (osteoarthritis and rheumatoid arthritis) and even in individuals without pathologies. These data confirm the complexity of the relationship of the HLA-B gene variants with SpA, since it is not possible to establish a diagnosis of SpA with these variants alone. However, we suggest that allele HLA-B40, in combination with some specific rheumatic bone manifestations, facilitates the diagnosis of SpA.


Subject(s)
Arthritis, Rheumatoid/diagnosis , HLA-B27 Antigen/genetics , HLA-B35 Antigen/genetics , HLA-B40 Antigen/genetics , Osteoarthritis/diagnosis , Polymorphism, Genetic , Spondylarthropathies/diagnosis , Alleles , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Body Remains , Bone and Bones/immunology , Bone and Bones/pathology , Climate , Cold Temperature , DNA, Ancient/analysis , Diagnosis, Differential , Female , Genetic Predisposition to Disease , HLA-B27 Antigen/immunology , HLA-B35 Antigen/immunology , HLA-B40 Antigen/immunology , History, Medieval , Humans , Joints/immunology , Joints/pathology , Male , Osteoarthritis/genetics , Osteoarthritis/immunology , Osteoarthritis/pathology , Paleopathology/methods , Spain , Spondylarthropathies/genetics , Spondylarthropathies/immunology , Spondylarthropathies/pathology
7.
Naturwissenschaften ; 105(9-10): 51, 2018 Aug 14.
Article in English | MEDLINE | ID: mdl-30291451

ABSTRACT

Inflammatory arthritis is documented for the first time in snakes. Ossification of the intervertebral capsule and zygapophyseal joints resulting in segmental vertebral fusion was observed in the aquatic Cretaceous snake Lunaophis aquaticus. Such pathologic alterations are pathognomonic for the spondyloarthropathy form of inflammatory arthritis. A survey of 2144 snakes in recent collections, performed to identify Holocene prevalence, revealed only two occurrences in extant snakes. The findings in Bitis gabonica and Elaphe taeniura were indistinguishable from those noted in Lunaophis aquaticus and identical to those previously recognized in modern varanids. The pathology likely represents a form of reactive arthritis related to enteropathic infection. While the disease probably did not affect general locomotion, its vertebral column position may have compromised mating.


Subject(s)
Fossils , Snakes/anatomy & histology , Spine/pathology , Spondylarthropathies/pathology , Animals , Biological Evolution , Spine/anatomy & histology
8.
Clin Immunol ; 183: 207-212, 2017 10.
Article in English | MEDLINE | ID: mdl-28390966

ABSTRACT

The IL-17/1L-23 axis is important in the pathogenesis of spondyloarthropathy. Innate cells produce IL-17 in addition to Th17 cells. We studied the frequencies of natural killer (NK) (total, CD56bright, CD56dim, perforin+ and granzyme+), NK-T, γδ-T, and IFN-γ+, IL-17+ NK and γδ-T cells in peripheral blood (PB) and synovial fluid (SF) of ReA/uSpA patients. PB from 45 patients and paired SF from 39 patients were studied, together with PB from 18 healthy controls (HC). The frequency of γδ-T cells was decreased (p<0.05) while IL-17 producing NK and γδ-T cells were increased (p<0.05) in PB of patients as compared to HC. In SF, CD56bright NK cells were increased (p<0.001) but had reduced expression of perforin and granzyme (p<0.0001) as compared to PB. Frequency of IL-17+, IFN-γ+ NK and γδ-T cells was higher in SF as compared to PB (p<0.05). We suggest that innate cells by producing pro-inflammatory cytokines may contribute to pathogenesis.


Subject(s)
Interferon-gamma/metabolism , Interleukin-17/metabolism , Killer Cells, Natural/metabolism , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Spondylarthropathies/pathology , T-Lymphocytes/metabolism , Adolescent , Adult , Arthritis, Reactive/pathology , Female , Humans , Immunity, Innate , Interferon-gamma/genetics , Interleukin-17/genetics , Killer Cells, Natural/immunology , Male , Prohibitins , Synovial Fluid , Young Adult
9.
Int J Mol Sci ; 19(1)2017 Dec 28.
Article in English | MEDLINE | ID: mdl-29283375

ABSTRACT

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.


Subject(s)
Antirheumatic Agents/therapeutic use , Gene Expression Regulation/drug effects , Mesenchymal Stem Cells/cytology , Ossification, Heterotopic/prevention & control , Spondylarthropathies/therapy , Stem Cell Transplantation/methods , Cartilage, Articular/drug effects , Cartilage, Articular/immunology , Cartilage, Articular/pathology , Dendritic Cells/drug effects , Dendritic Cells/immunology , Dendritic Cells/pathology , Gene Expression Regulation/immunology , Humans , Interleukin-12/genetics , Interleukin-12/immunology , Interleukin-17/genetics , Interleukin-17/immunology , Macrophages/drug effects , Macrophages/immunology , Macrophages/pathology , Mesenchymal Stem Cells/immunology , Monocytes/drug effects , Monocytes/immunology , Monocytes/pathology , Neutrophils/drug effects , Neutrophils/immunology , Neutrophils/pathology , Ossification, Heterotopic/genetics , Ossification, Heterotopic/immunology , Ossification, Heterotopic/pathology , Spondylarthropathies/genetics , Spondylarthropathies/immunology , Spondylarthropathies/pathology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology
10.
Rheumatology (Oxford) ; 55(4): 599-606, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26359330

ABSTRACT

Increased knowledge about pathological processes active in inflammatory joint diseases is needed to initiate personalized medicine based on targeted treatments in the future. The molecular and cellular pathways that are active during joint inflammation may differ between the various inflammatory joint diseases, between different patient subgroups within one disease, or even between different stages of the disease in a single patient. In this review, we evaluate synovial inflammation in terms of descriptive histopathology through to more functional studies on human synovial tissue inflammation in RA and SpA, in phenotypic subgroups of RA and SpA patients, and during the disease course of both diseases.


Subject(s)
Arthritis, Rheumatoid/pathology , Spondylarthropathies/pathology , Synovitis/pathology , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Gene Expression Profiling , Humans , Spondylarthropathies/genetics , Spondylarthropathies/immunology , Synovial Membrane/immunology , Synovial Membrane/pathology , Synovitis/genetics , Synovitis/immunology
11.
Ann Rheum Dis ; 74(11): 2016-21, 2015 Nov.
Article in English | MEDLINE | ID: mdl-24962871

ABSTRACT

OBJECTIVE: Investigating changes in patient classification (ASAS (Assessment of SpondyloArthritis international Society) axSpA criteria) based on evaluation of images of the sacro-iliac joints (MRI-SI and X-SI) by local and central readers. METHODS: The DESIR cohort included patients with inflammatory back pain (IBP; ≥3 months, but <3 years), suggestive of axSpA. Local radiologists/rheumatologists (local-reading) and two central readers (central-reading) evaluated baseline images. Agreement regarding positive MRI (pos-MRI) between central readers and between local-reading and central-reading was calculated (κs). Number of patients classified differently (ASAS criteria) by using local-reading instead of central-reading was calculated. RESULTS: Inter-reader agreement between the two central readers and between local-reading and central-reading was substantial (κ=0.73 and κ=0.70, respectively). In 89/663 MRI-SIs (13.4%) local-reading and central-reading disagreed; 38/223 patients (17.0%) with pos-MRI (local-reading) were negative by central-reading; 51/440 patients (11.6%) with neg-MRI (local-reading) were positive by central-reading.In 163/582 patients eligible for applying ASAS criteria (28.0%), local-reading and central-reading disagreed on positive imaging (MRI-SI and/or X-SI; κ=0.68). In 46/582 patients (7.9%) a different evaluation resulted in a different classification; 18/582 patients (3.1%) classified no-SpA (central-reading) were axSpA by local-reading; 28/582 patients (4.8%) classified axSpA (central-reading) were no-SpA by local-reading. Among axSpA patients (central-reading), 16/419 patients (3.8%) fulfilling imaging-arm by central-reading fulfilled clinical-arm by local-reading; 29/419 patients (6.9%) fulfilling clinical-arm by central-reading fulfilled also imaging-arm by local-reading. CONCLUSIONS: In patients with recent onset IBP, trained readers and local rheumatologists/radiologists agree well on recognising a pos-MRI. While disagreeing in 28% of the patients on positive imaging (MRI-SI and/or X-SI), classification of only 7.9% of the patients changed based on a different evaluation of images, showing the ASAS axSpA criteria's robustness.


Subject(s)
Back Pain/pathology , Radiology/standards , Rheumatology/standards , Sacroiliac Joint/pathology , Sacroiliitis/pathology , Spondylitis, Ankylosing/pathology , Adolescent , Adult , Back Pain/etiology , Cohort Studies , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Observer Variation , Prospective Studies , Sacroiliitis/complications , Severity of Illness Index , Spondylarthropathies/complications , Spondylarthropathies/pathology , Spondylitis, Ankylosing/complications , Young Adult
12.
Ann Rheum Dis ; 74(11): 1976-82, 2015 Nov.
Article in English | MEDLINE | ID: mdl-24925836

ABSTRACT

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.


Subject(s)
Back Pain/pathology , Bone Marrow/pathology , Edema/pathology , Sacroiliac Joint/pathology , Sacroiliitis/pathology , Spondylitis, Ankylosing/pathology , Adult , Back Pain/etiology , Cohort Studies , Edema/etiology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Sacroiliitis/complications , Sensitivity and Specificity , Spondylarthropathies/complications , Spondylarthropathies/pathology , Spondylitis, Ankylosing/complications , Uveitis, Anterior/complications
13.
Int J Immunogenet ; 42(1): 4-10, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25545293

ABSTRACT

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.


Subject(s)
HLA-B27 Antigen/immunology , Histocompatibility Antigens Class I/biosynthesis , Immunoglobulin Heavy Chains/biosynthesis , Monocytes/immunology , Spondylarthropathies/immunology , Adolescent , Adult , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , CD3 Complex/metabolism , Cell Line, Tumor , Female , Green Fluorescent Proteins/biosynthesis , Green Fluorescent Proteins/genetics , HLA-B27 Antigen/genetics , Humans , Lipopolysaccharide Receptors/metabolism , Male , Middle Aged , Spondylarthropathies/pathology , Synovial Fluid/cytology , Transfection , U937 Cells , Young Adult , beta 2-Microglobulin/biosynthesis
14.
J Biol Chem ; 288(15): 10882-9, 2013 Apr 12.
Article in English | MEDLINE | ID: mdl-23430249

ABSTRACT

The presentation of short viral peptide antigens by human leukocyte antigen (HLA) class I molecules on cell surfaces is a key step in the activation of cytotoxic T lymphocytes, which mediate the killing of pathogen-infected cells or initiate autoimmune tissue damage. HLA-B27 is a well known class I molecule that is used to study both facets of the cellular immune response. Using mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of HLA-B*2705(+) cells, we identified 200 naturally processed HLA-B*2705 ligands. Our analyses revealed that a change in the position (P) 2 anchor motif was detected in the 3% of HLA-B*2705 ligands identified. B*2705 class I molecules were able to bind these six GlnP2 peptides, which showed significant homology to pathogenic bacterial sequences, with a broad range of affinities. One of these ligands was able to bind with distinct conformations to HLA-B27 subtypes differentially associated with ankylosing spondylitis. These conformational differences could be sufficient to initiate autoimmune damage in patients with ankylosing spondylitis-associated subtypes. Therefore, these kinds of peptides (short, with GlnP2, and similar low affinity to all HLA-B27 subtypes tested but with unlike conformations in differentially ankylosing spondylitis-associated subtypes) must not be excluded from future researches involving potential arthritogenic peptides.


Subject(s)
HLA-B27 Antigen/immunology , Peptides/immunology , Spondylarthropathies/immunology , Amino Acid Motifs , Cell Line , HLA-B27 Antigen/genetics , HLA-B27 Antigen/metabolism , Humans , Peptides/genetics , Peptides/metabolism , Protein Binding/genetics , Protein Binding/immunology , Spondylarthropathies/genetics , Spondylarthropathies/metabolism , Spondylarthropathies/pathology
15.
BMC Musculoskelet Disord ; 15: 446, 2014 Dec 19.
Article in English | MEDLINE | ID: mdl-25526985

ABSTRACT

BACKGROUND: The objective of this study was to identify leukocyte cell types found within the synovia of patients with seronegative spondylarthropathies (SpA), such as ankylosing spondylitis (AS), using transcription based analyses. METHODS: Leukocyte transcriptional profiles obtained from the NCBI's gene expression omnibus and prediction analysis of microarrays (PAM) was used to identify 25-gene leukocyte metagenes. Subsequently, transcriptional profiles from murine and clinical models of AS and SpA were interrogated to characterize the local infiltration of leukocytes in SpA synovia. RESULTS: Analysis of a proteoglycan-induced murine model of AS reveals infiltration of dendritic cells, CD4+ T cells, monocytes, and natural killer cells to the spine. In human SpA and AS patients, transcriptional analysis of synovial biopsies revealed local infiltration of dendritic cells and CD4+ T cells. CONCLUSIONS: We identified leukocyte cell types that infiltrated the synovial of SpA patients. Our results imply a role for dendritic cells and CD4+ T cells in the local inflammation that underlies pathogenesis in patients with SpA.


Subject(s)
Immunity, Cellular/immunology , Leukocytes/immunology , Spondylarthropathies/blood , Spondylarthropathies/immunology , Synovial Fluid/immunology , Animals , Humans , Leukocytes/metabolism , Mice , Spondylarthropathies/pathology , Synovial Fluid/metabolism
16.
Eur Radiol ; 23(6): 1686-93, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23300035

ABSTRACT

OBJECTIVE: To test the hypothesis that microanatomical differences in joint disease localisation could be exploited using high-resolution MRI to better differentiate among rheumatoid arthritis (RA), spondyloarthritis/psoriatic arthritis (SpA/PsA) and osteoarthritis (OA) in clinical practice. METHODS: Sixty-nine patients with suspected inflammatory joint disease of the hand or feet underwent high-resolution MRI using a small loop coil. Images were scored blinded to the clinical status. Various joint changes like periostitis, osteitis, erosions, enthesitis and synovitis were recorded. The image-based diagnosis was compared with the clinical diagnosis. RESULTS: In 59.4 % of the patients the clinical diagnosis was confirmed on image analysis. This was high for OA (80 %), moderately good for RA (67 %) but only 50 % for SpA/PsA. The major difficulty was to distinguish OA from SpA/PsA where common imaging findings are evident including periostitis (SpA/PsA 45 %, OA 40 % compared with RA 0 %; P = 0.015). Likewise, osteitis was frequently detected in SpA/PsA (79 %) and OA (80 %) and less frequently in RA (42 %) (P = 0.014). CONCLUSION: Characterisation of inflammatory disorders of small joints merely using high-resolution MRI remains challenging especially in the differentiation between OA and PsA. These findings are likely explained by common microanatomical similarities in disease expression rather than limitations of imaging techniques. KEY POINTS: • High-resolution MRI is increasingly used to investigate joint disease. • Osteitis and periostitis occur in psoriatic and osteoarthritis (but not rheumatoid arthritis). • In severely affected patients the amount of synovitis and erosions is similar.


Subject(s)
Arthritis, Psoriatic/pathology , Arthritis, Rheumatoid/pathology , Hand Joints/pathology , Magnetic Resonance Imaging/methods , Osteoarthritis/pathology , Spondylarthropathies/pathology , Adult , Aged , Cross-Sectional Studies , Equipment Design , Female , Humans , Image Processing, Computer-Assisted/methods , Inflammation , Male , Middle Aged , Prospective Studies , Synovitis/pathology
17.
Radiographics ; 33(4): 933-56, 2013.
Article in English | MEDLINE | ID: mdl-23842966

ABSTRACT

The sacroiliac joints are involved in most cases of axial spondyloarthropathy, the first manifestation usually being sacroiliitis. A finding of sacroiliitis at radiography is the classic diagnostic hallmark of axial spondyloarthropathy. However, radiographic changes reflect structural damage rather than active inflammation, which may delay the diagnosis by several years. In the past decade, the field of spondyloarthropathy has undergone major changes, largely driven by the development of new drugs for the treatment of ankylosing spondylitis. In recent years, the Assessment of SpondyloArthritis international Society has focused on the reassessment of existing classification criteria and the development and validation of diagnostic tools to facilitate early diagnosis and assessment of treatment response. Magnetic resonance (MR) imaging is the most recent innovation and the important change with respect to the previously established classification criteria. This modality has become an integral part of managing patients with sacroiliitis. MR imaging can serve as a biomarker of disease activity, allows monitoring, and can provide guidance for the treatment of affected patients, and it will likely become even more central to the care of these patients. Familiarity with the anatomy, anatomic variants, and physiologic changes of the sacroiliac joints is important for correctly interpreting findings and avoiding misdiagnosis.


Subject(s)
Axis, Cervical Vertebra/pathology , Forecasting , Magnetic Resonance Imaging/trends , Sacroiliitis/etiology , Sacroiliitis/pathology , Spondylarthropathies/complications , Spondylarthropathies/pathology , Adult , Humans , Magnetic Resonance Imaging/standards , Male , Practice Guidelines as Topic
18.
J Korean Med Sci ; 28(9): 1289-92, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24015032

ABSTRACT

Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in initiating acute gouty arthritis. The objectives of this study were to measure the levels of caspase-1 in synovial fluid in gout and various arthritides, and to elucidate the clinical significance of caspase-1 levels in synovial fluid. Caspase-1, IL-1ß, IL-18, and uric acid were measured in synovial fluid from 112 patients with gout and other arthritides, such as rheumatoid arthritis, osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis, and spondyloarthropathy was 35.9 ± 86.7, 49.7 ± 107.7, 2.1 ± 7.0, and 152.6 ± 155.7 pg/mL, respectively. The mean level and the frequency of high levels (≥125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than those in the other arthritides including gout. Caspase-1 was detectible in the synovial fluid of patients with the various arthritides. Contrary to our hypothesis, the caspase-1 level in the synovial fluid of patients with gout was not higher than in that of other arthritides. High levels of caspase-1 may be helpful in differentiating spondyloarthropathy from other arthritides.


Subject(s)
Caspase 1/analysis , Gout/enzymology , Spondylarthropathies/enzymology , Synovial Fluid/enzymology , Adult , Aged , Arthritis, Rheumatoid/enzymology , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Female , Gout/metabolism , Gout/pathology , Humans , Interleukin-18/analysis , Interleukin-1beta/analysis , Leukocyte Count , Male , Middle Aged , Osteoarthritis/enzymology , Osteoarthritis/metabolism , Osteoarthritis/pathology , Spondylarthropathies/metabolism , Spondylarthropathies/pathology , Synovial Fluid/metabolism , Uric Acid/analysis
20.
Int J Paleopathol ; 42: 1-13, 2023 09.
Article in English | MEDLINE | ID: mdl-37343491

ABSTRACT

OBJECTIVE: This study aimed to determine the prevalence of the ossification of the ligamenta flava (OLF) among skeletal remains from Poland. MATERIALS AND METHODS: 124 skeletons aged 25 years and older were analyzed. The presence and size of OLF were observed macroscopically. OLF was recorded at the cranial and caudal attachment sites of each vertebra. The following factors were analyzed: age at death, sex, and presence of other spondyloarthropathies. RESULTS: The crude prevalence of OLF in the analyzed series was 68.55 %. OLF was located most frequently in the lower thoracic spine. A statistically significant relationship was observed between the presence of OLF and age at death. OLF coincided with degenerative spondyloarthropathies of the thoracolumbar spine. CONCLUSIONS: The results of this study indicate that OLF was not a rare condition in past populations of European ancestry. Analysis of OLF prevalence in skeletal materials can contribute to reconstruction of the conditions and lifestyles of past people. SIGNIFICANCE: This study shed new light on the prevalence of OLF and provides information on the variability of OLF in past European populations. The evaluation of the prevalence of OLF represents an important contribution to the field of paleopathology in understanding disease changes in prehistoric and historic human populations. LIMITATIONS: The analyzed material came from unknown populations without demographic data. Sex and age at death were assessed using standard anthropological methods. SUGGESTIONS FOR FURTHER RESEARCH: It is important to understand the influence of sociocultural factors and physical activity patterns on the development of OLF.


Subject(s)
Ligamentum Flavum , Spondylarthropathies , Humans , Ligamentum Flavum/pathology , Ligamentum Flavum/surgery , Osteogenesis , Prevalence , Poland , Spondylarthropathies/pathology
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