scholarly journals Is HLA-B27 Increased in Patients Diagnosed with Undifferentiated Arthritis? Results from the Leiden Early Arthritis Cohort

2014 ◽  
Vol 41 (10) ◽  
pp. 1948-1951 ◽  
Author(s):  
Floris van Gaalen ◽  
Rosaline van den Berg ◽  
Inge Verhoog ◽  
Joris Schonkeren ◽  
Annette van der Helm-van Mil ◽  
...  
Keyword(s):  
Family History ◽  
International Society ◽  
Early Arthritis ◽  
Healthy Controls ◽  
Hla B27 ◽  
Undifferentiated Arthritis ◽  
Asas Criteria ◽  
Peripheral Spondyloarthritis

Objective.Undifferentiated arthritis (UA) is a common form of arthritis. According to the Assessment of Spondyloarthritis international Society (ASAS) criteria for peripheral spondyloarthritis (pSpA), HLA-B27 can be used to help classify patients with pSpA. We tested whether HLA-B27 is increased in patients diagnosed with UA.Methods.Prevalence of HLA-B27 was compared between healthy controls and patients with UA. SpA features were compared between HLA-B27-positive and -negative UA, and SpA.Results.We found 10.1% of UA (38/375) versus 7.2% (403/5584) of controls were HLA-B27-positive (OR 1.5, 95% CI 1.0–2.1; p = 0.037). HLA-B27-positive patients with UA had more SpA features than HLA-B27-negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001). Family history and preceding infection were features more common in HLA-B27-positive than in HLA-B27-negative UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%, p = 0.04). After HLA-B27 testing, 21 additional patients (5.6%) with UA could potentially have been classified with pSpA according to the ASAS criteria.Conclusion.HLA-B27 is more common in patients with UA than in controls. However, the yield of HLA-B27 testing in UA is low. Our results suggest that HLA-B27 testing should be reserved for patients with additional SpA features.

scholarly journals Reactive arthritis and undifferentiated peripheral spondyloarthritis share human leucocyte antigen B27 subtypes and serum and synovial fluid cytokine profiles

Rheumatology ◽  
2020 ◽  
Author(s):  
Jyoti Ranjan Parida ◽  
Sandeep Kumar ◽  
Sakir Ahmed ◽  
Smriti Chaurasia ◽  
Ratnadeep Mukherjee ◽  
...  
Keyword(s):  
Statistical Difference ◽  
Human Leucocyte Antigen ◽  
Healthy Controls ◽  
Hla B27 ◽  
Serum Cytokine ◽  
Cytokine Profiles ◽  
Cytokine Levels ◽  
Peripheral Spondyloarthritis ◽  
Multiplex Cytokine ◽  
Age And Sex

Abstract Objectives Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA. Methods ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels. Results In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients. Conclusion ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.

Performance of the Assessment in Spondyloarthritis International Society Classification for Axial and Peripheral Spondyloarthritis in an Established Clinical Cohort: Comparison with Criteria Sets of Amor and the European Spondylarthropathy Study Group

2012 ◽  
Vol 39 (4) ◽  
pp. 816-821 ◽  
Author(s):  
PETER P. CHEUNG ◽  
SIMON PATERNOTTE ◽  
VINCENT BURKI ◽  
ANNE DURNEZ ◽  
MURIEL ELHAI ◽  
...  
Keyword(s):  
International Society ◽  
Inflammatory Back Pain ◽  
Study Group ◽  
C Reactive Protein ◽  
Peripheral Arthritis ◽  
Protein Levels ◽  
Reactive Protein ◽  
Asas Criteria ◽  
Established Disease ◽  
Peripheral Spondyloarthritis

Objective.To evaluate the performance of the Assessment in Spondyloarthritis International Society (ASAS) criteria (axial or peripheral) against the Amor and European Spondylarthropathy Study Group criteria in established spondyloarthritis (SpA).Methods.Rheumatologist-diagnosed patients with SpA were retrospectively classified according to the different criteria sets. Clinical characteristics of patients fulfilling all 3 criteria were compared with those who did not, by nonparametric statistics.Results.ASAS classified 90% of the 231 patients, with 169 (73%) fulfilling all 3 criteria sets. Multivariate analysis showed the 62 patients not fulfilling all criteria sets were older at symptom onset (p < 0.001) and less likely to have inflammatory back pain (p < 0.001), peripheral arthritis (p < 0.001), or elevated C-reactive protein levels (p = 0.034).Conclusion.ASAS criteria can be used in established disease.

scholarly journals MICA*019 Allele and Soluble MICA as Biomarkers for Ankylosing Spondylitis in Taiwanese

2021 ◽  
Vol 11 (6) ◽  
pp. 564
Author(s):  
Chin-Man Wang ◽  
Keng-Poo Tan ◽  
Yeong-Jian Jan Wu ◽  
Jing-Chi Lin ◽  
Jian-Wen Zheng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Healthy Controls ◽  
Hla B27 ◽  
Host Immune Responses ◽  
Histocompatibility Complex ◽  
High Level ◽  
Coding Snp

MICA (major histocompatibility complex class I chain-related gene A) interacts with NKG2D on immune cells to regulate host immune responses. We aimed to determine whether MICA alleles are associated with AS susceptibility in Taiwanese. MICA alleles were determined through haplotype analyses of major MICA coding SNP (cSNP) data from 895 AS patients and 896 normal healthy controls in Taiwan. The distributions of MICA alleles were compared between AS patients and normal healthy controls and among AS patients, stratified by clinical characteristics. ELISA was used to determine soluble MICA (sMICA) levels in serum of AS patients and healthy controls. Stable cell lines expressing four major MICA alleles (MICA*002, MICA*008, MICA*010 and MICA*019) in Taiwanese were used for biological analyses. We found that MICA*019 is the only major MICA allele significantly associated with AS susceptibility (PFDR = 2.25 × 10−115; OR, 14.90; 95% CI, 11.83–18.77) in Taiwanese. In addition, the MICA*019 allele is associated with syndesmophyte formation (PFDR = 0.0017; OR, 1.69; 95% CI, 1.29–2.22) and HLA-B27 positivity (PFDR = 1.45 × 10−33; OR, 28.79; 95% CI, 16.83–49.26) in AS patients. Serum sMICA levels were significantly increased in AS patients as compared to healthy controls. Additionally, MICA*019 homozygous subjects produced the highest levels of sMICA, compared to donors with other genotypes. Furthermore, in vitro experiments revealed that cells expressing MICA*019 produced the highest level of sMICA, as compared to other major MICA alleles. In summary, the MICA*019 allele, producing the highest levels of sMICA, is a significant risk factor for AS and syndesmophyte formation in Taiwanese. Our data indicate that a high level of sMICA is a biomarker for AS.

Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Jere Häyrynen ◽  
Maija Kärkkäinen ◽  
Aulikki Kononoff ◽  
Leena Arstila ◽  
Pia Elfving ◽  
...  
Keyword(s):  
Early Arthritis ◽  
Joint Disease ◽  
Type I ◽  
Type Ii ◽  
Newly Diagnosed ◽  
Seronegative Arthritis ◽  
Inflammatory Joint Disease ◽  
Undifferentiated Arthritis ◽  
Serum Samples ◽  
The Mean

AbstractThe aim of the study was to describe automated immunoassays for autoantibodies to homocitrulline or citrulline containing telopeptides of type I and II collagen in various disease categories in an early arthritis series.Serum samples were collected from 142 patients over 16 years of age with newly diagnosed inflammatory joint disease. All samples were analyzed with an automated inhibition chemiluminescence immunoassay (CLIA) using four different peptide pairs, each consisting of a biotinylated antigen and an inhibiting peptide. Assays were performed with an IDS-iSYS analyzer. Autoantibodies binding to homocitrulline and citrulline containing C-telopeptides of type I (HTELO-I, TELO-I) and type II collagens (HTELO-II, TELO-II) were analyzed.The mean ratio of HTELO-I inhibition in seropositive and seronegative rheumatoid arthritis (RA) was 3.07 (95% CI 1.41–11.60), p=0.003, and in seropositive and seronegative undifferentiated arthritis (UA) 4.90 (1.85–14.49), p<0.001. The respective mean ratios in seropositive and seronegative RA and UA were in TELO-I 8.72 (3.68–58.01), p<0.001 and 3.13 (1.49–6.16), p=0.008, in HTELO-II 7.57 (3.18–56.60), p<0.001 and 2.97 (1.23–6.69), p=0.037, and in TELO-II 3.01 (1.30–9.51), p=0.002 and 3.64 (1.86–7.65), p=0.008. In reactive arthritis, ankylosing spondylitis, psoriatic arthritis and unspecified spondyloarthritis the inhibition levels were similar to those observed in seronegative RA or UA.Autoantibodies binding to homocitrulline or citrulline containing telopeptides of type I and II collagen did not differ significantly. They were highest among patients with seropositive disease and they differentiated seropositive and seronegative arthritis.

scholarly journals Is a positive family history of spondyloarthritis relevant for diagnosing axial spondyloarthritis once HLA-B27 status is known?

Rheumatology ◽  
2019 ◽  
Vol 58 (9) ◽  
pp. 1649-1654 ◽  
Author(s):  
Miranda van Lunteren ◽  
Désirée van der Heijde ◽  
Alexandre Sepriano ◽  
Inger J Berg ◽  
Maxime Dougados ◽  
...  
Keyword(s):  
Back Pain ◽  
Family History ◽  
Anterior Uveitis ◽  
Chronic Back Pain ◽  
Axial Spondyloarthritis ◽  
Positive Family History ◽  
Hla B27 ◽  
Acute Anterior Uveitis ◽  
Negative Results ◽  
History Of

Abstract Objectives A positive family history (PFH) of spondyloarthritis, in particular a PFH of AS or acute anterior uveitis, is associated with HLA-B27 carriership in chronic back pain patients. As it is unknown, the study aimed to investigate if a PFH contributes to diagnosing axial spondyloarthritis (axSpA) once HLA-B27 status is known. Methods In axSpA-suspected patients from the Assessment of SpondyloArthritis international Society (ASAS), DEvenir des Spondyloarthropathies Indifférenciéés Récentes (DESIR) and SPondyloArthritis Caught Early (SPACE) cohorts, logistic regression analyses were performed with HLA-B27 status and PFH according to the ASAS definition (ASAS-PFH) as determinants and clinical axSpA diagnosis as outcome at baseline. Analyses were repeated with a PFH of AS or acute anterior uveitis. Results In total, 1818 patients suspected of axSpA were analysed (ASAS n = 594, DESIR n = 647, and SPACE n = 577). In patients from the ASAS, DESIR and SPACE cohorts, respectively 23%, 39% and 38% had an ASAS-PFH, 52%, 58% and 43% were HLA-B27 positive, and 62%, 47% and 54% were diagnosed with axSpA. HLA-B27 was independently associated with an axSpA diagnosis in each cohort but an ASAS-PFH was not [ASAS cohort: HLA-B27 odds ratio (OR): 6.9 (95% CI: 4.7, 10.2), ASAS-PFH OR: 0.9 (95% CI: 0.6, 1.4); DESIR: HLA-B27 OR: 2.1 (95% CI: 1.5, 2.9), ASAS-PFH OR: 1.0 (95% CI 0.7, 1.3); SPACE: HLA-B27 OR: 10.4 (95% CI: 6.9, 15.7), ASAS-PFH OR: 1.0 (95% CI: 0.7, 1.5)]. Similar negative results were found for PFH of AS and acute anterior uveitis. Conclusion In three independent cohorts with different ethnical backgrounds, ASAS, DESIR and SPACE, a PFH was not associated independently of HLA-B27 with a diagnosis of axSpA. This indicates that in the vast majority of patients presenting with back pain, a PFH does not contribute to the likelihood of an axSpA diagnosis if HLA-B27 status is known.

Diagnosis, classification, and management of peripheral spondyloarthritis

2016 ◽  
Author(s):  
Martin Rudwaleit ◽  
Atul Deodhar
Keyword(s):  
Bacterial Infections ◽  
Axial Skeleton ◽  
Controlled Clinical Trial ◽  
Peripheral Arthritis ◽  
Asas Criteria ◽  
Inflammatory Bowel ◽  
Peripheral Spondyloarthritis ◽  
Chronic Course ◽  
Diagnosis Classification ◽  
Better Than

Spondyloarthritis (SpA) can affect the axial skeleton (axSpA) but also manifest as peripheral arthritis, enthesitis, and dactylitis (peripheral SpA). Peripheral SpA can occur after bacterial infections (reactive arthritis) or be associated with psoriasis or inflammatory bowel disease. The arthritis is usually asymmetric, affects predominantly the lower extremity, and can be self-limiting but can also run a chronic course. The frequency of HLA-B27 is around 50% in purely peripheral SpA, while it is 70–90% in axSpA. For classification, the Amor, ESSG, or more recent ASAS criteria for peripheral SpA can be used. The ASAS criteria are likely to capture early peripheral SpA better than the other two. Therapy includes NSAIDs, local steroid injections, and synthetic disease-modifying antirheumatic drugs, of which sulfasalazine is best studied and the preferred drug for peripheral arthritis. A recent, placebo-controlled clinical trial with adalimumab may lead to the first approval of a biologic in peripheral SpA.

scholarly journals Peripheral disease contributes significantly to the level of disease activity in axial spondyloarthritis

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000802 ◽  
Author(s):  
Janneke J de Winter ◽  
Jacqueline E Paramarta ◽  
Henriëtte M de Jong ◽  
Marleen G van de Sande ◽  
Dominique L Baeten
Keyword(s):  
Back Pain ◽  
Disease Activity ◽  
International Society ◽  
Axial Spondyloarthritis ◽  
Real Life ◽  
The Other ◽  
Peripheral Arthritis ◽  
Asas Criteria ◽  
Observational Cohort ◽  
Axial Disease

ObjectiveSpondyloarthritis (SpA) can encompass axial, peripheral and extra-articular disease manifestations. Patients are classified as axial or peripheral SpA depending on the presence or absence of current back pain, independently of the other disease manifestations. Therefore, we aimed to assess the percentage of patients with axial SpA with peripheral disease and how this peripheral disease contributes to the overall disease activity.MethodsPrevalence and disease activity of peripheral disease manifestations were assessed in a real-life observational cohort of 314 patients with the clinical diagnosis of SpA and fulfilling the Assessment of SpondyloArthritis international Society (ASAS) criteria.ResultsOf the 314 patients fulfilling the ASAS criteria, 230 fulfilled the axial and 84 the peripheral SpA criteria. Of the 230 patients with axial SpA, 49% had purely axial disease without peripheral disease manifestations whereas 51% had combined axial (back pain) and peripheral (arthritis, enthesitis and/or dactylitis) disease. The latter group had the highest disease activity in comparison with pure axial SpA as well as with peripheral SpA.ConclusionHalf of the patients classified as axial SpA according to the ASAS criteria also have peripheral disease manifestations such as arthritis, enthesitis and/or dactylitis. These peripheral disease manifestations contribute significantly to overall disease activity.

scholarly journals A logistic regression analysis of risk factors in ME/CFS pathogenesis

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Eliana M. Lacerda ◽  
Keith Geraghty ◽  
Caroline C. Kingdon ◽  
Luigi Palla ◽  
Luis Nacul
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Regression Analysis ◽  
Risk Factor ◽  
Family History ◽  
Disease Onset ◽  
Healthy Controls ◽  
Lower Income ◽  
Wide Range ◽  
History Of

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease, whose exact cause remains unclear. A wide range of risk factors has been proposed that helps understanding potential disease pathogenesis. However, there is little consistency for many risk factor associations, thus we undertook an exploratory study of risk factors using data from the UK ME/CFS Biobank participants. We report on risk factor associations in ME/CFS compared with multiple sclerosis participants and healthy controls. Methods This was a cross-sectional study of 269 people with ME/CFS, including 214 with mild/moderate and 55 with severe symptoms, 74 people with multiple sclerosis (MS), and 134 healthy controls, who were recruited from primary and secondary health services. Data were collected from participants using a standardised written questionnaire. Data analyses consisted of univariate and multivariable regression analysis (by levels of proximity to disease onset). Results A history of frequent colds (OR = 8.26, P <= 0.001) and infections (OR = 25.5, P = 0.015) before onset were the strongest factors associated with a higher risk of ME/CFS compared to healthy controls. Being single (OR = 4.41, P <= 0.001), having lower income (OR = 3.71, P <= 0.001), and a family history of anxiety is associated with a higher risk of ME/CFS compared to healthy controls only (OR = 3.77, P < 0.001). History of frequent colds (OR = 6.31, P < 0.001) and infections before disease onset (OR = 5.12, P = 0.005), being single (OR = 3.66, P = 0.003) and having lower income (OR = 3.48, P = 0.001), are associated with a higher risk of ME/CFS than MS. Severe ME/CFS cases were associated with lower age of ME/CFS onset (OR = 0.63, P = 0.022) and a family history of neurological illness (OR = 6.1, P = 0.001). Conclusions Notable differences in risk profiles were found between ME/CFS and healthy controls, ME/CFS and MS, and mild-moderate and severe ME/CFS. However, we found some commensurate overlap in risk associations between all cohorts. The most notable difference between ME/CFS and MS in our study is a history of recent infection prior to disease onset. Even recognising that our results are limited by the choice of factors we selected to investigate, our findings are consistent with the increasing body of evidence that has been published about the potential role of infections in the pathogenesis of ME/CFS, including common colds/flu.

scholarly journals HLA B-27 Subtypes in Turkish Patients with Spondyloarthropathy and Healthy Controls

2004 ◽  
Vol 20 (6) ◽  
pp. 309-312 ◽  
Author(s):  
Fatma Savran Oguz ◽  
Lale Ocal ◽  
Ali Sarper Diler ◽  
Hilmi Ozkul ◽  
Faruk Asicioglu ◽  
...  
Keyword(s):  
Turkish Population ◽  
Study Group ◽  
Healthy Controls ◽  
Hla B27 ◽  
Caucasian Patients ◽  
Male Patients ◽  
Different Populations ◽  
The Difference ◽  
Turkish Patients ◽  
Predominant Allele

The frequency and the distribution of HLA-B27 subtypes in spondylarthropathy (SpA) patients and controls were investigated in a sample Turkish population. B27 subtyping was performed by PCR-SSP method in two groups: 49 unrelated HLA-B27 positive Turkish patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group Criteria, and 55 HLA-B27 positive healthy controls. The frequency of HLA-B∗27 was 2.6% in the Turkish population, and B∗2705 was the predominant allele among patients with SpA. The difference was mainly between male patients and male controls The proportion of B∗2705 among B27-positive patients and controls was significantly different (P = 0.02). Our study supports other reports from different populations which showed that B∗2705 and B∗2702 were more frequent in Caucasian patients with SpA.

scholarly journals GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis

2020 ◽  
Author(s):  
Sara Fuentelsaz-Romero ◽  
Andrea Cuervo ◽  
Lizbeth Estrada-Capetillo ◽  
Raquel Celis ◽  
Raquel García-Campos ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Inflammatory Marker ◽  
Macrophage Polarization ◽  
Activin A ◽  
Healthy Controls ◽  
Undifferentiated Arthritis ◽  
Gm Csf ◽  
Macrophage Density ◽  
Anti Inflammatory

Abstract Background and Aims: GM-CSF-dependent macrophage polarization hasbeen demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.Methods:Synovial tissue (ST)from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12 and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.Results:Synovial stromal cells (FAP+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypesshowed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA and established RA and PsA patients, respectively.Conclusions: GM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.

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