HLA-B27

HLA-B27

This test is used to diagnose spondyloarthritis.

See also 2 related tests 0 related guides Test Guide List

HLA-B27

Test Summary

 

HLA-B27

Test Code: 528, 15584

 

Clinical use

  • Diagnose spondyloarthritis

Clinical background

The term “spondyloarthritis” (SpA) encompasses a group of inflammatory rheumatic diseases that cause arthritis; these include radiographic axial SpA (ie, ankylosing spondylitis), nonradiographic axial SpA, reactive arthritis, psoriatic arthritis, and inflammatory bowel disease–associated arthritis. SpA can be subdivided into axial SpA, which involves the spine and sacroiliac joints, and peripheral SpA, which involves peripheral arthritis, enthesitis, and dactylitis.1,2 Depending on the disease type, SpA is treatable with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs (DMARDs), including biologics (eg, tumor necrosis factor inhibitors) and synthetic DMARDs (eg, methotrexate).3,4 Identification of individuals with SpA is important because treatment can alleviate symptoms and potentially slow radiographic progression.3,5 However, diagnosis is challenging, especially for axial SpA because of the high prevalence of chronic back pain in the general population and limitations of a clinical examination.6

Testing for human leukocyte antigen (HLA)-B27 can help identify individuals with SpA.1,2 HLA-B27 is most strongly associated with radiographic axial SpA, with approximately 85% to 95% of patients carrying the gene.7 However, not every HLA-B27-positive person develops SpA. About 6% of the US population is estimated to carry HLA-B27, but SpA has an estimated prevalence of only 0.4% to 1.3%.8,9 Thus, HLA-B27 testing is not diagnostic by itself and must be used in combination with other clinical and radiographic criteria.

The Assessment of Spondyloarthritis International Society (ASAS) released classification criteria for axial SpA in 20091 and peripheral SpA in 2011.2 The ASAS criteria were developed to be applicable to nonradiographic and early stage SpA.1 The axial SpA criteria have radiographic (imaging) and clinical arms, both of which incorporate HLA-B27 testing (Table); these criteria have a reported sensitivity of 82.9% and a specificity of 84.4%.1 The peripheral SpA criteria also incorporate HLA-B27 testing and have a reported sensitivity of 77.8% and a specificity of 82.2%.2

HLA-B27 status can be determined by antigen or molecular testing. ASAS guidelines do not differentiate between the methods, possibly because results are almost always concordant. A study of 543 patients with suspected spondyloarthropathy demonstrated 99% concordance between an antigen assay and a polymerase chain reaction (PCR)-based molecular assay.10 Discordant results can be caused by cross-reactivity with other HLA-B antigens (eg, HLA-B07 or HLA-B40).11 Thus, a molecular test may be slightly more reliable. Quest Diagnostics offers an antigen test (test code 528) and a molecular test (test code 15584) for the detection of HLA-B27.

Table. ASAS Classification Criteria for Spondyloarthritis

Axial SpA1

Peripheral SpA2

Patients with back pain for ≥3 months who are <45 years at onset and meet criteria in clinical or imaging arm

Patients with peripheral manifestations only

Clinical arm
HLA-B27 and ≥2 other SpA features from footnote a

Imaging arm
Sacroiliitis on imaging and
≥1 SpA feature from footnote a

Arthritis, enthesitis, or dactylitis and ≥1 SpA feature from footnote b or ≥2 other SpA features from footnote c
a HLA-B27, inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn's or ulcerative colitis, response to NSAIDs, family history of SpA, elevated C-reactive protein levels.
b HLA-B27, uveitis, psoriasis, Crohn's or ulcerative colitis, preceding infection, sacroiliitis on imaging.
c Arthritis, enthesitis, dactylitis, inflammatory back pain, family history of SpA.

Individuals suitable for testing

  • Individuals with clinical or radiographic indications of SpA

Methods

  • HLA-B27 Antigen (test code 528): detect HLA-B27 antigen using antigen-antibody binding and flow cytometry
  • HLA-B27 DNA Typing (test code 15584): detect HLA-B27 allele using PCR amplification and sequence-specific probes

Interpretive information

A positive HLA-B27 result is consistent with SpA (radiographic axial SpA, nonradiographic axial SpA, reactive arthritis, psoriatic arthritis, or inflammatory bowel disease–associated arthritis). However, most people who are HLA-B27 positive do not develop an associated condition. Thus, diagnosis and classification should be based on multiple criteria.1,2

A negative HLA-B27 result does not rule out conditions associated with HLA-B27; the allele is not always present in patients with these conditions.

References

  1. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777-783. doi:10.1136/ard.2009.108233

  2. Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2011;70(1):25-31. doi:10.1136/ard.2010.133645

  3. Ward MM, Deodhar A, Gensler LS, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-1613. doi:10.1002/art.41042

  4. Molto A, Sieper J. Peripheral spondyloarthritis: concept, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2018;32(3):357-368. doi:10.1016/j.berh.2019.02.010

  5. Sepriano A, Ramiro S, van der Heijde D, et al. Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference. RMD Open. 2021;7(2):e001654. doi:10.1136/rmdopen-2021-001654

  6. Danve A, Deodhar A. Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities. Clin Rheumatol. 2019;38(3):625-634. doi:10.1007/s10067-018-4397-3

  7. Hayward RJ, Machado PM. Classification criteria in axial spondyloarthritis: what have we learned; where are we going? Rheum Dis Clin North Am. 2020;46(2):259-274. doi:10.1016/j.rdc.2020.01.008

  8. Reveille JD, Hirsch R, Dillon CF, et al. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407-1411. doi:10.1002/art.33503

  9. Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci. 2011;341(4):284-286. doi:10.1097/MAJ.0b013e31820f8c99

  10. Jang HS, Proos A, Koe L, et al. High accuracy of HLA-B*27 genotyping by allele-specific real-time polymerase chain reaction in a heterogeneous population compared to flow cytometry and single nucleotide polymorphism detection assays. Pathology. 2020;52(2):256-261. doi:10.1016/j.pathol.2019.09.013

  11. Levering WH, Wind H, Sintnicolaas K, et al. Flow cytometric HLA-B27 screening: cross-reactivity patterns of commercially available anti-HLA-B27 monoclonal antibodies with other HLA-B antigens. Cytometry B Clin Cytom. 2003;54(1):28-38. doi:10.1002/cyto.b.10022


     

Content reviewed 10/2024

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This test is used to diagnose spondyloarthritis.

Test Guide List

HLA-B27

Test Summary

 

HLA-B27

Test Code: 528, 15584

 

Clinical use

  • Diagnose spondyloarthritis

Clinical background

The term “spondyloarthritis” (SpA) encompasses a group of inflammatory rheumatic diseases that cause arthritis; these include radiographic axial SpA (ie, ankylosing spondylitis), nonradiographic axial SpA, reactive arthritis, psoriatic arthritis, and inflammatory bowel disease–associated arthritis. SpA can be subdivided into axial SpA, which involves the spine and sacroiliac joints, and peripheral SpA, which involves peripheral arthritis, enthesitis, and dactylitis.1,2 Depending on the disease type, SpA is treatable with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs (DMARDs), including biologics (eg, tumor necrosis factor inhibitors) and synthetic DMARDs (eg, methotrexate).3,4 Identification of individuals with SpA is important because treatment can alleviate symptoms and potentially slow radiographic progression.3,5 However, diagnosis is challenging, especially for axial SpA because of the high prevalence of chronic back pain in the general population and limitations of a clinical examination.6

Testing for human leukocyte antigen (HLA)-B27 can help identify individuals with SpA.1,2 HLA-B27 is most strongly associated with radiographic axial SpA, with approximately 85% to 95% of patients carrying the gene.7 However, not every HLA-B27-positive person develops SpA. About 6% of the US population is estimated to carry HLA-B27, but SpA has an estimated prevalence of only 0.4% to 1.3%.8,9 Thus, HLA-B27 testing is not diagnostic by itself and must be used in combination with other clinical and radiographic criteria.

The Assessment of Spondyloarthritis International Society (ASAS) released classification criteria for axial SpA in 20091 and peripheral SpA in 2011.2 The ASAS criteria were developed to be applicable to nonradiographic and early stage SpA.1 The axial SpA criteria have radiographic (imaging) and clinical arms, both of which incorporate HLA-B27 testing (Table); these criteria have a reported sensitivity of 82.9% and a specificity of 84.4%.1 The peripheral SpA criteria also incorporate HLA-B27 testing and have a reported sensitivity of 77.8% and a specificity of 82.2%.2

HLA-B27 status can be determined by antigen or molecular testing. ASAS guidelines do not differentiate between the methods, possibly because results are almost always concordant. A study of 543 patients with suspected spondyloarthropathy demonstrated 99% concordance between an antigen assay and a polymerase chain reaction (PCR)-based molecular assay.10 Discordant results can be caused by cross-reactivity with other HLA-B antigens (eg, HLA-B07 or HLA-B40).11 Thus, a molecular test may be slightly more reliable. Quest Diagnostics offers an antigen test (test code 528) and a molecular test (test code 15584) for the detection of HLA-B27.

Table. ASAS Classification Criteria for Spondyloarthritis

Axial SpA1

Peripheral SpA2

Patients with back pain for ≥3 months who are <45 years at onset and meet criteria in clinical or imaging arm

Patients with peripheral manifestations only

Clinical arm
HLA-B27 and ≥2 other SpA features from footnote a

Imaging arm
Sacroiliitis on imaging and
≥1 SpA feature from footnote a

Arthritis, enthesitis, or dactylitis and ≥1 SpA feature from footnote b or ≥2 other SpA features from footnote c
a HLA-B27, inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn's or ulcerative colitis, response to NSAIDs, family history of SpA, elevated C-reactive protein levels.
b HLA-B27, uveitis, psoriasis, Crohn's or ulcerative colitis, preceding infection, sacroiliitis on imaging.
c Arthritis, enthesitis, dactylitis, inflammatory back pain, family history of SpA.

Individuals suitable for testing

  • Individuals with clinical or radiographic indications of SpA

Methods

  • HLA-B27 Antigen (test code 528): detect HLA-B27 antigen using antigen-antibody binding and flow cytometry
  • HLA-B27 DNA Typing (test code 15584): detect HLA-B27 allele using PCR amplification and sequence-specific probes

Interpretive information

A positive HLA-B27 result is consistent with SpA (radiographic axial SpA, nonradiographic axial SpA, reactive arthritis, psoriatic arthritis, or inflammatory bowel disease–associated arthritis). However, most people who are HLA-B27 positive do not develop an associated condition. Thus, diagnosis and classification should be based on multiple criteria.1,2

A negative HLA-B27 result does not rule out conditions associated with HLA-B27; the allele is not always present in patients with these conditions.

References

  1. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68(6):777-783. doi:10.1136/ard.2009.108233

  2. Rudwaleit M, van der Heijde D, Landewé R, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis. 2011;70(1):25-31. doi:10.1136/ard.2010.133645

  3. Ward MM, Deodhar A, Gensler LS, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2019;71(10):1599-1613. doi:10.1002/art.41042

  4. Molto A, Sieper J. Peripheral spondyloarthritis: concept, diagnosis and treatment. Best Pract Res Clin Rheumatol. 2018;32(3):357-368. doi:10.1016/j.berh.2019.02.010

  5. Sepriano A, Ramiro S, van der Heijde D, et al. Biological DMARDs and disease modification in axial spondyloarthritis: a review through the lens of causal inference. RMD Open. 2021;7(2):e001654. doi:10.1136/rmdopen-2021-001654

  6. Danve A, Deodhar A. Axial spondyloarthritis in the USA: diagnostic challenges and missed opportunities. Clin Rheumatol. 2019;38(3):625-634. doi:10.1007/s10067-018-4397-3

  7. Hayward RJ, Machado PM. Classification criteria in axial spondyloarthritis: what have we learned; where are we going? Rheum Dis Clin North Am. 2020;46(2):259-274. doi:10.1016/j.rdc.2020.01.008

  8. Reveille JD, Hirsch R, Dillon CF, et al. The prevalence of HLA-B27 in the US: data from the US National Health and Nutrition Examination Survey, 2009. Arthritis Rheum. 2012;64(5):1407-1411. doi:10.1002/art.33503

  9. Reveille JD. Epidemiology of spondyloarthritis in North America. Am J Med Sci. 2011;341(4):284-286. doi:10.1097/MAJ.0b013e31820f8c99

  10. Jang HS, Proos A, Koe L, et al. High accuracy of HLA-B*27 genotyping by allele-specific real-time polymerase chain reaction in a heterogeneous population compared to flow cytometry and single nucleotide polymorphism detection assays. Pathology. 2020;52(2):256-261. doi:10.1016/j.pathol.2019.09.013

  11. Levering WH, Wind H, Sintnicolaas K, et al. Flow cytometric HLA-B27 screening: cross-reactivity patterns of commercially available anti-HLA-B27 monoclonal antibodies with other HLA-B antigens. Cytometry B Clin Cytom. 2003;54(1):28-38. doi:10.1002/cyto.b.10022


     

Content reviewed 10/2024

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