A Nationwide Questionnaire Survey on the Prevalence of Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis in Japan

Abstract Objective This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-ax SpA), and the positive rate of human leukocyte antigen (HLA) among these patients in Japan. Methods The first survey was conducted in 2221 randomly selected facilities (26.3%) in September, 2018, where the patients with AS/nr-ax SpA were taken care of from January to December, 2017. We estimated the total number of these patients using response and extraction rate. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B 27 positivity rate and clinical features. Results The estimated total number of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400–3900) and 800 (530–1100), suggesting that the prevalence of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5 % (76/137) of patients with AS were HLA-B27 positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. Conclusion This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features.

Download Full-text

1267Prevalence and HLA-B27 Positivity Rate among Patients with Ankylosing Spondylitis/Non-Radiographic Axial Spondyloarthritis in Japan

International Journal of Epidemiology ◽

10.1093/ije/dyab168.423 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Yuri Matsubara ◽

Yosikazu Nakamura ◽

Tetsuya Tomita

Keyword(s):

Ankylosing Spondylitis ◽

Axial Spondyloarthritis ◽

Age Of Onset ◽

Human Leukocyte ◽

Nationwide Survey ◽

Hla B27 ◽

Sacroiliac Joints ◽

Radiographic Findings ◽

Leukocyte Antigen ◽

To Receive

Abstract Background Ankylosing spondylitis (AS) causes severe chronic inflammation of the spine and sacroiliac joints, leading to severe physical dysfunctions. Non-radiographic axial spondyloarthritis (nr-ax SpA) is a newly categorized disease in SpA that shows SpA without definite radiographic findings in sacroiliac joint. Although human leukocyte antigen (HLA) positivity is related to these diseases, little is known about the prevalence of these diseases and HLA-B27 positivity in Japan. Methods A nationwide survey was conducted from January to December 2017. 2221/8456 facilities (26.3%) were selected randomly as a target sample, comprising all three departments: orthopedics, pediatrics, and rheumatology. We estimated the number of these patients by using response and extraction rate, and calculated the HLA-B27 positivity rate. Results We estimated the prevalence of AS and nr-ax SpA as 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. HLA-B27 test was performed in 60% of patients with AS, of which 55.5% being HLA-B27 positive; however, they were less likely to receive HLA-B27 test if their estimated age of onset was over 50 years. Conclusions The prevalence in AS and nr-ax SpA and their HLA-B27 positivity rate in Japan were lower compared to other countries. Further studies will be required to reveal the association between HLA-B27 and the clinical features. Key messages The prevalence of AS and nr-ax SpA in Japan are estimated to be 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively, and are lower than those in other countries. In addition, HLA-B27 positivity rate was lower.

Download Full-text

Epidemiology of axial spondyloarthritis

10.1093/med/9780198734444.003.0002 ◽

2016 ◽

Author(s):

Lianne Gensler ◽

Michael Weisman ◽

Liron Caplan

Keyword(s):

External Validity ◽

Inflammatory Arthritis ◽

Axial Spondyloarthritis ◽

Strong Association ◽

Human Leukocyte ◽

Epidemiological Studies ◽

Hla B27 ◽

Sacroiliac Joints ◽

Leukocyte Antigen ◽

Inflammatory Bowel

Axial spondyloarthritis (axSpA) is an inflammatory arthritis of the sacroiliac joints and spine. The prototype is ankylosing spondylitis, the radiographic form of the disease; however, more recently, an earlier or less-differentiated presentation has been described termed non-radiographic axial spondyloarthritis (nr-axSpA). Extra-articular manifestations commonly include anterior uveitis, inflammatory bowel disease, and psoriasis. There is a strong association with the human leukocyte antigen B27 (HLA-B27) allele, and the prevalence of the disease tends to follow the frequency of the allele. Epidemiological studies in axSpA are relevant in the population studied and therefore have limited external validity. This chapter describes the epidemiology of axSpA.

Download Full-text

The pathogenesis of ankylosing spondylitis

Neurosurgical FOCUS ◽

10.3171/foc/2008/24/1/e3 ◽

2008 ◽

Vol 24 (1) ◽

pp. E3 ◽

Cited By ~ 18

Author(s):

Mohammed F. Shamji ◽

Mohammed Bafaquh ◽

Eve Tsai

Keyword(s):

Ankylosing Spondylitis ◽

Molecular Mimicry ◽

Human Leukocyte ◽

Axial Skeleton ◽

Chronic Inflammatory Disease ◽

The Body ◽

Hla B27 ◽

Leukocyte Antigen ◽

Molecular Events ◽

Microbial Tolerance

✓ Ankylosing spondylitis (AS) is a chronic inflammatory disease that can cause significant functional complications by affecting the sacroiliac joints and axial skeleton. Despite a longstanding knowledge about the familial associations of this disease, particularly among patients positive for human leukocyte antigen (HLA)–B27, the fundamental pathogenetic mechanism by which this disease arises in genetically susceptible individuals remains ill defined. Furthermore, the molecular predilection for characteristic articular site involvement remains under ongoing investigation. Current theories about the HLA-B27 association range from the presentation of novel arthritogenic peptides, to abnormal autoimmune stimulation, to anomalous microbial tolerance. The immune effectors of this damage include CD4+, CD8+, and natural killer cells, with marked heterogeneity at different sites. Biomechanical stresses may trigger this disease by exposing the body to previously immune-sequestered autoantigens or by providing a route for bacterial seeding. Environmental triggers such as infection have not been definitively established but may represent a primary pathogenic step in a molecular-mimicry process. In this article, the authors review the current literature on the origin and pathophysiology of AS, focusing on genetic and molecular associations, consequent pathomechanisms, and associated triggers. An improved understanding of the sequence of molecular events that predispose and initiate the onset of this disease will allow for more specific and targeted therapy and better avoidance of the significant side effects of systemic immunomodulation.

Download Full-text

HLA-B27 is a Risk Factor for Rheumatoid Arthritis: Suggestion for an Evidence-based Update

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692117666190408113012 ◽

2020 ◽

Vol 17 (1) ◽

pp. 7-10

Author(s):

Seyyed Amir Yasin Ahmadi ◽

Reza Mohammadrezaei-Khorramabadi ◽

Saber Abbaszadeh ◽

Jafar Rezaian ◽

Farhad Shahsavar

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factor ◽

Ankylosing Spondylitis ◽

Odds Ratio ◽

Meta Analysis ◽

Human Leukocyte ◽

Evidence Based ◽

Hla B27 ◽

Leukocyte Antigen ◽

And Personalized Medicine

Previously, the association of human leukocyte antigen (HLA)-B27 with ankylosing spondylitis has been investigated as original and meta-analysis studies. However, the association of HLA-B27 with rheumatoid arthritis is not currently investigated as a meta-analysis. Hence, in this letter, a brief meta-analysis on this association will be performed. Although there were some studies on the association of RA and HLA-B27, however, there was not a pooled odds ratio reported in textbooks. Based on this brief metaanalysis, number 2.687 can be reported as the odds ratio of this association. It shows that this association is neither sensitive nor specific, but can be an idea for pharmacogenomics and personalized medicine as a potential risk factor. Such other associations should be reported numerically and updated in textbooks.

Download Full-text

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

RMD Open ◽

10.1136/rmdopen-2020-001206 ◽

2020 ◽

Vol 6 (2) ◽

pp. e001206 ◽

Cited By ~ 1

Author(s):

Mohammad H Derakhshan ◽

Linda Dean ◽

Gareth T Jones ◽

Stefan Siebert ◽

Karl Gaffney

Keyword(s):

Ankylosing Spondylitis ◽

Axial Spondyloarthritis ◽

Human Leukocyte ◽

Prescribing Patterns ◽

British Society ◽

Tnf Inhibitor ◽

Hla B27 ◽

Patient Reported ◽

Bowel Diseases ◽

Biologics Register

ObjectivesExtra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.MethodsClinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.ResultsAAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.ConclusionThe higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.

Download Full-text

Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar

International Journal of Rheumatology ◽

10.1155/2012/860213 ◽

2012 ◽

Vol 2012 ◽

pp. 1-3 ◽

Cited By ~ 11

Author(s):

M. H. Abdelrahman ◽

S. Mahdy ◽

I. A. Khanjar ◽

A. M. Siam ◽

H. A. Malallah ◽

...

Keyword(s):

New York ◽

Major Histocompatibility Complex ◽

Ankylosing Spondylitis ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Hla B27 ◽

Cross Sectional ◽

Leukocyte Antigen ◽

Histocompatibility Complex ◽

Class 1

Background and Objectives. The human leukocyte antigen HLA-B27 is a class 1 antigen of the major histocompatibility complex and is strongly associated with ankylosing spondylitis (AS). The purpose of the present study is to investigate the distribution of HLA-B27 in patients with AS of different ethnic groups in Qatar.Design and Setting. Study design was cross-sectional and the setting was rheumatology clinics of Hamad General Hospital in Qatar where most of ankylosing spondylitis patients are followed up.Patients and Methods. Patients with diagnosis of AS who met the New York modified criteria for AS were tested for HLA-B27. 119 patients were tested for HLA-B27: 66 Arabs, 52 Asians (Indians, Pakistanis, Bengalis, and Iranians), and one Western (Irish).Results. Of all the individuals, 82 were positive (69%) for HLA-B27. Among the Arabs, 49/66 were positive (74%). Among the Asians, 32/52 were positive (61%). Furthermore, Qatari patients (10 males and one female) 9 were positive (82%), 14/19 Jordanians/Palestinians were positive, and 9/10 (90%) Egyptians were positive. Among the Asians, 19/26 Indians were positive (73%), which was similar to the Arabs.Conclusion. HLA-B27 in our small group of Arabs is present in 74%. Comparison with other data will be presented in detail.

Download Full-text

Sacroiliac radiographic progression in recent onset axial spondyloarthritis: the 5-year data of the DESIR cohort

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2017-211596 ◽

2017 ◽

Vol 76 (11) ◽

pp. 1823-1828 ◽

Cited By ~ 62

Author(s):

Maxime Dougados ◽

Alexandre Sepriano ◽

Anna Molto ◽

Miranda van Lunteren ◽

Sofia Ramiro ◽

...

Keyword(s):

New York ◽

Structural Damage ◽

Radiographic Progression ◽

Axial Spondyloarthritis ◽

Human Leukocyte ◽

Hla B27 ◽

Recent Onset ◽

Leukocyte Antigen ◽

Radiographic Changes ◽

Generalised Estimating Equations

ObjectiveTo estimate sacroiliac joint radiographic (X-SIJ) progression in patients with axial spondyloarthritis (axSpA) and to evaluate the effects of inflammation on MRI (MRI-SIJ) on X-SIJ progression.MethodsX-SIJ and MRI-SIJ at baseline and after 2 and 5 years in patients with recent onset axSpA from the DESIR cohort were scored by three central readers. Progression was defined as (1) the shift from non-radiographic (nr) to radiographic (r) sacroiliitis (by modified New York (mNY) criteria) or alternative criteria, (2) a change of at least one grade or (3) a change of at least one grade but ignoring a change from grade 0 to 1. The effects of baseline inflammation on MRI-SIJ on 5-year X-SIJ damage (mNY) were tested by generalised estimating equations.ResultsIn 416 patients with pairs of baseline and 5-year X-SIJ present, net progression occurred in 5.1% (1), 13.0% (2) and 10.3% (3) respectively, regarding a shift from nr-axSpA to r-axSpA (1), a change of at least one grade (2) or a change of at least one grade but ignoring a change from grade 0 to 1 (3). Baseline MRI-SIJ predicted structural damage after 5 years in human leukocyte antigen-B27 (HLA-B27) positive (OR 5.39 (95% CI 3.25 to 8.94)) and in HLA-B27 negative (OR 2.16 (95% CI 1.04 to 4.51)) patients.ConclusionsFive-year progression of X-SIJ damage in patients with recent onset axSpA is limited but present beyond measurement error. Baseline MRI-SIJ inflammation drives 5-year radiographic changes.

Download Full-text

Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.092312 ◽

2008 ◽

Vol 68 (1) ◽

pp. 107-109 ◽

Cited By ~ 14

Author(s):

K A Guthrie ◽

N R Tishkevich ◽

J L Nelson

Keyword(s):

Rheumatoid Arthritis ◽

Human Leukocyte Antigen ◽

Age Of Onset ◽

Human Leukocyte ◽

Paternal Allele ◽

Hla Alleles ◽

Leukocyte Antigen ◽

The North ◽

Significant Difference ◽

Hla Genotype

Objectives:Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.Methods:We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC).Results:Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ⩾45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women.Conclusions:Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.

Download Full-text

Axial Involvement in Psoriatic Arthritis: Effect on Peripheral Arthritis and Differential Features With Axial Spondyloarthritis in South America

The Journal of Rheumatology ◽

10.3899/jrheum.201627 ◽

2021 ◽

pp. jrheum.201627

Author(s):

Rodrigo García Salinas ◽

Einer Sanchez Prado ◽

Santiago Ruta

Keyword(s):

Psoriatic Arthritis ◽

Ankylosing Spondylitis ◽

South America ◽

Axial Spondyloarthritis ◽

Hla B27 ◽

Skin Involvement ◽

Peripheral Arthritis ◽

Male Sex ◽

Reported Data ◽

Axial Involvement

Reported data of axial involvement in psoriatic arthritis (PsA) are variable (25–70%). This variability is mainly linked to different ways of defining this feature. Gladman1 established that the prevalence of axial involvement in PsA was close to 50% and that it is associated with HLA-B27. Likewise, psoriasis (PsO) spondylitis, unlike ankylosing spondylitis (AS), is characterized by not having a greater preponderance of the male sex, greater skin involvement, and a less severe course.2

Download Full-text