HLA B27 antigen in Middle Eastern and Arab countries: systematic review of the strength of association with axial spondyloarthritis and methodological gaps

Abstract

BackgroundAxial spondyloarthritis (AxSpA) is a relatively frequent and debilitating disease, with a prevalence ranging from 0.1 to 2% in the Caucasian population. Current Assessment of Spondyloarthritis International Society (ASAS) classification criteria of AxSpA rely either on sacroiliitis on imaging plus one SpA feature or positive HLAB27 antigen plus two SpA features, in a patient with chronic low back pain and age at onset of less than 45 years. Therefore, HLA-B27 is a central feature in SpA classification and plays a pivotal role in referral strategies and early diagnosis. The primary objective of the study is to review the prevalence of HLA-B27 in normal and AxSpA populations in Middle Eastern and Arab Countries and to assess the strength of association between HLA-B27 antigen and AxSpA. The secondary objective is to identify the gaps in the methodology of the studies and suggest a framework for future research.MethodsStudies were included in the analysis if they reported prevalence of HLA-B27 in AxSpA and/or general population and if they covered geographical location in the Middle East or Arab countries in the Mediterranean basin. Odds ratios (OR) were calculated for each country, as a measure of the strength of association between HLA-B27 and AxSpA, compared to the normal population, using the two-by-two frequency table. Available data from the literature were analyzed according to the following quality indicators: sample size, method of HLA-B27 testing, presence of control group and external validity.ResultsTwenty-seven studies were analyzed. HLAB27 prevalence in the normal population ranged from 0.3% (Oman) to 6.8% (Turkey). HLA-B27 prevalence in AxSpA ranged from 26.2% (Lebanon) to 91% (Turkey). HLA-B27 prevalence in all SpA ranged from 13.87% (Lebanon) to 69.43% (Kuwait). Peripheral SpA was less associated with HLA-B27 than AxSpA, indicating the need of differentiating between the two entities when calculating prevalence. When available (8 studies), the OR ranged from 21.63 (Morocco) to 105.6 (Syria). The high heterogeneity between the results can be due to differences in methodology: study sample size, different classification criteria, absence of control groups, HLA-B27 testing method.ConclusionsThe prevalence of HLA-B27 in the normal population is significantly lower in the Middle Eastern and Arab countries than in Western Countries. However, HLA-B27 testing can be useful for AxSpA positive diagnosis, given the high OR. Heterogeneity between countries may be due to methodological differences.

HLA‐B27 prevalence in axial spondyloarthritis patients and in blood donors in a Lebanese population: Results from a nationwide study

“…Our study confirmed the lower prevalence of HLA‐B27 in axSpA patients (41.1%) and BD participants (3.8%) in Lebanon, compared to northern populations . These results are in line with the prevalence found in normal populations from the Arab and Middle Eastern region (0.3%‐6.8%) but are still lower than the published prevalences for axSpA (42.7%‐84%) …”

“…It is a class I antigen of the major histocompatibility complex that is present in 6%‐8% of the general population and in 80%‐95% of AS patients in western European and North American populations . However, the prevalence of HLA‐B27 in axSpA patients is found to be lower in Japan and in most Arab and Middle Eastern populations, compared to western European populations, possibly due to different genetic backgrounds . The lowest figures in the region were found in Lebanon with a prevalence of 26.3% in AS, 13.8% in SpA and 1.4% in the general population, according to the latest published study in 1997 .…”

Acute Anterior Uveitis in patients with ankylosing spondylitis in northeast of Iran

“…The positivity rate of HLA-B27 in patients with AS has been reported at 72% [13], 73% [23], 74.8% [31], and 76.2% [32], which are close to that reported in the present study. These percentages are significantly higher than the rate of HLA-B27 positivity in the general population in Iran (less than 4%) [33,34]. HLA-B27 is the strongest genetic factor associated with AS and AAU, and a higher prevalence of AAU [28] and more severe SpA is observed in HLA-B27 positive patients [35].…”

Gender differences in ankylosing spondylitis patients: Relation to clinical characteristics, functional status and disease activity

“…The most important limitation is the small number of patients which makes precise generalized conclusions potentially arguable. Nonetheless, AS may be even rarer in the Middle Eastern and Arab countries [32]. A longitudinal study with further indepth analysis is recommended to verify the reached findings, to determine the response to medications, detect the disease outcome and any confounding factors.…”