HLA-B27: Understanding Your Blood Test Series

1. Overview: What this test reveals and why it is important

HLA‑B27 is not a typical blood test that measures a concentration or enzyme activity. It is a genetic marker – specifically, a human leukocyte antigen (HLA) class I surface protein encoded by the HLA‑B locus on chromosome 6. The test detects the presence or absence of the HLA‑B27 allele.

This allele is strongly associated with a group of inflammatory rheumatic diseases known as spondyloarthropathies. The most important of these are:

· Ankylosing spondylitis (AS) – the strongest association; >90% of Caucasian AS patients are HLA‑B27 positive.

· Reactive arthritis (Reiter syndrome) – following certain genitourinary or enteric infections.

· Enteropathic arthritis – associated with inflammatory bowel disease (Crohn disease, ulcerative colitis).

· Psoriatic arthritis – particularly the axial (spine) subtype.

· Juvenile idiopathic arthritis – especially the enthesitis‑related arthritis subtype.

· Acute anterior uveitis – isolated eye inflammation.

Important principles:

· HLA‑B27 is a risk factor, not a diagnostic test. The vast majority (80–95%) of individuals with HLA‑B27 never develop an associated disease. Conversely, a negative HLA‑B27 does not exclude these conditions.

· The test is most useful when clinical suspicion of spondyloarthritis is moderate to high. A positive result increases the likelihood of disease; a negative result reduces it.

· Ethnicity profoundly affects prevalence: HLA‑B27 is present in 6–8% of Caucasians, 2–4% of Africans, 1% of Japanese, and up to 25–50% in certain Native American populations.

· HLA‑B27 is a lifelong, unchanging genetic trait. Once tested, it never needs to be repeated.

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2. What does it measure

a. Units of measurement

· Qualitative: Positive or negative.

· Some laboratories report semi‑quantitative results using flow cytometry (e.g., mean fluorescence intensity) or PCR‑based allele typing, but the clinical interpretation remains binary.

b. Normal Range and Interpretation

Negative:

· Absence of HLA‑B27 allele. This is the expected finding in most healthy individuals.

Positive:

· Presence of at least one copy of HLA‑B27 allele. Inheritance is autosomal codominant.

Prevalence of HLA‑B27 in selected populations (approximate):

· Caucasians: 6–8%

· African Americans: 2–4%

· Japanese: 0.5–1%

· Han Chinese: 2–6%

· Thai: 8–12%

· Native Alaskans / Haida: 25–50%

Interpretation notes:

· A positive HLA‑B27 in a patient with inflammatory back pain, sacroiliitis on imaging, or uveitis strongly supports a diagnosis of spondyloarthritis.

· A positive HLA‑B27 in an asymptomatic individual has no clinical significance and does not warrant treatment or further investigation.

· A negative HLA‑B27 does not rule out spondyloarthritis – 10% of AS patients and a larger proportion of psoriatic or enteropathic arthritis patients are HLA‑B27 negative.

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3. Other factors connected to this

a. Direct correlation (factors that directly influence test result)

· Genetics:

· HLA‑B27 is inherited in an autosomal dominant pattern with incomplete penetrance.

· First‑degree relatives of HLA‑B27‑positive AS patients have a higher risk of carrying the allele and developing disease.

· Ethnicity: As above; determines pre‑test probability.

· Technical factors:

· Flow cytometry: Detects surface expression of HLA‑B27 protein on lymphocytes. Rarely, cross‑reactivity with other HLA‑B alleles can cause false positives.

· PCR (polymerase chain reaction) / DNA typing: Gold standard; identifies specific alleles (HLA‑B*27:01 to *27:106). Virtually no false positives; distinguishes subtypes with different disease associations.

· False negatives: Can occur with certain rare subtypes not recognised by monoclonal antibodies in flow cytometry; PCR resolves this.

b. Indirect correlation (factors that influence disease risk in HLA‑B27‑positive individuals)

Not all HLA‑B27 carriers develop disease. Additional triggers are required:

· Environmental triggers:

· Bacterial infections: Certain Gram‑negative bacteria (Chlamydia trachomatis, Salmonella, Shigella, Yersinia, Campylobacter) can trigger reactive arthritis in HLA‑B27‑positive individuals.

· Gut microbiome dysbiosis: Emerging evidence suggests that intestinal inflammation and altered microbiota may contribute to AS pathogenesis.

· Other genetic factors:

· ERAP1 (endoplasmic reticulum aminopeptidase 1) polymorphisms interact with HLA‑B27 to increase AS risk.

· IL23R, IL1R2, ANTXR2 and other loci also contribute.

· Mechanical stress: Entheseal (sites where tendons/ligaments attach to bone) microtrauma may trigger inflammation in genetically susceptible individuals.

· Smoking:

· Strongly associated with more severe AS and worse functional outcomes. Not clearly linked to disease initiation, but cessation improves prognosis.

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4. Disorders related to abnormal values

a. When HLA‑B27 is positive (clinically significant – but only in the right clinical context)

Spondyloarthritis (SpA):

· Ankylosing spondylitis (AS):

· Chronic inflammatory disease predominantly affecting the sacroiliac joints and spine.

· 90% of Caucasian AS patients are HLA‑B27 positive. The risk of developing AS is 5–6% in HLA‑B27‑positive individuals (much higher if also family history).

· Clinical features: inflammatory back pain (morning stiffness, improvement with exercise), alternating buttock pain, enthesitis (Achilles, plantar fascia), reduced spinal mobility, uveitis.

· Radiographic: sacroiliitis (plain X‑ray, MRI), syndesmophytes, bamboo spine.

· Reactive arthritis (ReA):

· Sterile inflammatory arthritis occurring 1–4 weeks after genitourinary (C. trachomatis) or enteric (Salmonella, Shigella, Yersinia, Campylobacter) infection.

· Classic triad: arthritis, urethritis/cervicitis, conjunctivitis (incomplete forms common).

· 30–50% of patients are HLA‑B27 positive; positivity is associated with more severe, chronic course.

· Psoriatic arthritis (PsA):

· Approximately 10–25% of PsA patients are HLA‑B27 positive, particularly those with axial involvement (spine and sacroiliac joints).

· Peripheral arthritis and psoriasis are less strongly linked to HLA‑B27.

· Enteropathic arthritis (EA):

· Associated with Crohn disease and ulcerative colitis.

· 40–50% of axial EA patients are HLA‑B27 positive; peripheral EA is not associated.

· Juvenile idiopathic arthritis (JIA) – enthesitis‑related arthritis subtype:

· 60–80% of these patients are HLA‑B27 positive.

· Usually affects boys > age 6; involves lower limb entheses and sacroiliac joints.

· Acute anterior uveitis (AAU):

· 50% of AAU patients are HLA‑B27 positive.

· Typically unilateral, recurrent, sudden‑onset, resolves within 3 months.

· Often associated with underlying undiagnosed spondyloarthritis.

Other conditions with increased HLA‑B27 prevalence (weaker associations):

· Anterior uveitis with hypopyon.

· Aortic regurgitation (due to aortitis in long‑standing AS).

· Cardiac conduction defects (complete heart block).

· IgA nephropathy – some studies show modest association.

b. When HLA‑B27 is negative

· Does not exclude spondyloarthritis. Seronegative AS (10% of Caucasians, higher in other ethnicities) and most peripheral PsA and EA are HLA‑B27 negative.

· Normal finding in the vast majority of healthy individuals.

· Negative HLA‑B27 with high clinical suspicion – diagnosis relies on imaging (MRI sacroiliitis) and clinical criteria.

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5. Best way to address aberrant levels

Important principle: HLA‑B27 positivity is not treated. The associated inflammatory disease, if present, is treated. There is no medication or intervention to alter HLA‑B27 status. Management focuses on controlling inflammation, relieving symptoms, maintaining function, and preventing structural damage.

a. Quick ways or using Medications

Treatment of spondyloarthritis (AS, PsA, ReA, EA) is guided by rheumatology.

General principles:

· Nonsteroidal anti‑inflammatory drugs (NSAIDs):

· First‑line symptomatic therapy for axial disease.

· Ibuprofen, naproxen, diclofenac, indomethacin, celecoxib.

· Use lowest effective dose; monitor gastrointestinal, renal, and cardiovascular risk.

· Continuous versus on‑demand use: continuous NSAIDs may retard radiographic progression in AS (controversial).

· Conventional synthetic disease‑modifying antirheumatic drugs (csDMARDs):

· Methotrexate, sulfasalazine, leflunomide:

· Ineffective for axial disease but may help peripheral arthritis.

· Sulfasalazine is the preferred csDMARD for peripheral arthritis in AS/SpA.

· Methotrexate commonly used in psoriatic arthritis (peripheral and skin).

· Biologic DMARDs (bDMARDs):

· TNF inhibitors: adalimumab, etanercept, infliximab, golimumab, certolizumab.

· First‑line biologics for active AS despite NSAIDs.

· Highly effective for axial disease, peripheral arthritis, enthesitis, and uveitis.

· Etanercept is less effective for uveitis.

· IL‑17 inhibitors: secukinumab, ixekizumab.

· Alternative first‑line or after TNF failure; effective for axial and peripheral disease.

· IL‑23 inhibitors: ustekinumab, guselkumab – effective for PsA, not for AS (negative trials).

· JAK inhibitors: tofacitinib, upadacitinib – emerging evidence in AS and PsA.

· Corticosteroids:

· Limited role in axial disease.

· Intra‑articular injections for peripheral arthritis or sacroiliitis.

· Topical corticosteroids for uveitis (ophthalmology guidance).

· Systemic steroids generally avoided (high doses required, side effects, flares upon withdrawal).

· For reactive arthritis:

· Treat the triggering infection (if still present) with appropriate antibiotics.

· NSAIDs first‑line; persistent arthritis may require DMARDs or biologics.

· For enteropathic arthritis:

· Coordinate with gastroenterologist; treat underlying IBD.

· Sulfasalazine, methotrexate, TNF inhibitors effective for both joint and bowel disease.

· IL‑17 inhibitors may exacerbate IBD – avoid.

Do not self‑prescribe – all DMARDs and biologics require specialist supervision.

b. Using Supplements or Holistic medicine

Supplements are adjunctive only; they do not replace disease‑modifying therapy. Evidence for modifying SpA disease activity is modest. Always discuss with rheumatologist before starting supplements.

For supporting joint health and reducing inflammation:

· Omega‑3 fatty acids (EPA/DHA):

· Anti‑inflammatory; may reduce NSAID requirement.

· Preferred source: Algae oil – sustainable, plant‑based, direct EPA/DHA, no marine contaminants.

· Avoid conventional fish oil (overfishing, ocean pollution, ethical concerns).

· Dose: 2–4 g/day EPA/DHA.

· Curcumin (turmeric):

· Inhibits NF‑κB and pro‑inflammatory cytokines.

· Small studies suggest benefit in arthritis.

· Use phytosomal, liposomal, or with piperine for bioavailability.

· Avoid products with added synthetic folic acid or cyanocobalamin.

· Vitamin D:

· Immunomodulatory; deficiency is common in AS and correlates with disease activity.

· Preferred: D3 (cholecalciferol) from lichen.

· Dose: 600–2000 IU/day for maintenance; higher for deficiency correction.

· Vitamin K2 (menaquinone‑7):

· May promote bone health and reduce syndesmophyte formation (theoretical, limited evidence).

· Preferred source: natto‑derived MK‑7 (fermented soy); plant‑based, sustainable.

· Boswellia serrata (frankincense):

· Anti‑inflammatory; inhibits 5‑lipoxygenase.

· Some evidence in arthritis; limited in SpA.

· Preferred source: standardised extract with ≥30% boswellic acids.

· Ginger (Zingiber officinale):

· Anti‑inflammatory; may reduce pain.

· Use fresh or powdered; standardised extracts available.

· Green tea catechins (EGCG):

· Antioxidant, anti‑inflammatory; may reduce cartilage degradation.

· Use beverage (2–3 cups/day) rather than concentrated extracts (hepatotoxicity risk).

· Probiotics / prebiotics:

· Modulate gut microbiota; emerging evidence suggests benefit in AS (reduced disease activity, improved gut barrier).

· Preferred sources: fermented plant foods (kimchi, sauerkraut, kombucha, miso, tempeh); standardised probiotic supplements with documented strains (e.g., Bifidobacterium, Lactobacillus).

· Zinc:

· Essential for immune function; deficiency may exacerbate inflammation.

· Preferred form: zinc picolinate or zinc citrate.

· Dose: 15–30 mg elemental zinc/day; monitor copper.

· Selenium:

· Antioxidant; may support immune regulation.

· Brazil nuts (1–2/day) or supplement 50–100 mcg/day as selenomethionine.

Supplements to AVOID:

· Synthetic folic acid – not contraindicated unless on methotrexate; but methylfolate is preferred.

· Cyanocobalamin – use methylcobalamin.

· High‑dose vitamin E – may impair immune function.

· Echinacea, astragalus, alfalfa sprouts – theoretical immune stimulation; may exacerbate autoimmunity.

· Unregulated herbal blends – hepatotoxicity risk; no proven benefit.

General caution: Many herbal supplements are not standardised and may interact with biologics or immunosuppressants. Do not use without consulting rheumatologist.

c. Using Diet and Foods (following a plant‑forward, ecologically sustainable approach)

Diet is a cornerstone of managing systemic inflammation in spondyloarthritis. A well‑designed, nutrient‑dense, anti‑inflammatory plant‑based diet can complement medical therapy, reduce cardiovascular risk (elevated in AS), improve gut microbiome, and enhance quality of life.

Core dietary principles – what to emphasise:

· Anti‑inflammatory dietary pattern:

· Mediterranean‑style plant‑forward diet – abundant vegetables, fruits, legumes, whole grains, nuts, seeds, olive oil.

· High in polyphenols, fibre, unsaturated fats, and antioxidants.

· Low in refined carbohydrates, added sugars, and saturated fats.

· Evidence: Improves inflammatory markers, reduces cardiovascular risk, and may reduce disease activity in inflammatory arthritis.

· Adequate protein intake:

· Essential for tissue repair, immune function, and maintaining muscle mass (sarcopenia is common in AS due to chronic inflammation and reduced physical activity).

· Plant‑based protein sources (hierarchy adhered):

· Primary: legumes (lentils, chickpeas, beans, soy products – tofu, tempeh, edamame).

· Fungi / algae: mycoprotein (Quorn), spirulina, chlorella.

· Biotechnology: precision‑fermented dairy proteins (animal‑free whey, casein) – acceptable emerging options.

· Dairy / eggs: permitted but not emphasised; low‑fat fermented dairy (yoghurt, kefir) if tolerated (lactose intolerance is common).

· Meat, poultry, fish: deliberately omitted. Effective plant‑based alternatives exist to meet all nutritional requirements. There is no need for animal products to support health in spondyloarthritis.

· Omega‑3 fatty acids:

· ALA sources: ground flaxseeds, chia seeds, hemp seeds, walnuts.

· Direct EPA/DHA: microalgae (spirulina, chlorella – limited amounts); algae oil supplements for therapeutic doses.

· Polyphenol‑rich foods:

· Berries, green tea, dark chocolate (≥70% cocoa), extra virgin olive oil, turmeric, ginger, cruciferous vegetables (broccoli, kale, Brussels sprouts), onions, garlic, apples, citrus.

· Vitamin D:

· Sunlight exposure primary; fortified plant milks; supplement from lichen if needed.

· Calcium:

· Critical for AS patients (osteoporosis risk is high due to chronic inflammation and reduced mobility).

· Plant sources: fortified plant milks (soy, almond, oat), calcium‑set tofu, tempeh, tahini, kale, bok choy, broccoli, okra, almonds.

· Iron:

· Anaemia of chronic disease is common; iron deficiency may occur with concurrent NSAID use (gastrointestinal blood loss).

· Plant sources: lentils, chickpeas, tofu, pumpkin seeds, quinoa, fortified cereals, dark leafy greens (cooked).

· Enhance absorption with vitamin C; avoid tea/coffee with meals.

· Folate:

· Avoid folic acid‑fortified foods. Choose unfortified grains and products.

· Natural folate sources: dark leafy greens, legumes, asparagus, beets, avocado, citrus fruits.

· Vitamin B12:

· No reliable plant‑based whole food source. Must be supplemented – methylcobalamin from fermentation, non‑animal, ecologically responsible.

· Fiber:

· High‑fibre diets (≥30 g/day) reduce systemic inflammation and support gut microbiome health.

· Sources: oats, barley, legumes, vegetables, fruits, nuts, seeds.

· Starch modification (controversial, unproven):

· Some hypothesise that a low‑starch diet reduces gut load of Klebsiella pneumoniae and other bacteria implicated in AS pathogenesis.

· Evidence is weak and not recommended as standard therapy. If trialled, do so under dietitian supervision for a defined period, with careful monitoring of disease activity. Do not implement restrictive diets without professional guidance.

What to avoid or severely limit:

· Ultra‑processed foods, refined carbohydrates, added sugars – promote inflammation, insulin resistance, and dysbiosis.

· Excess sodium – many AS patients have hypertension or corticosteroid‑induced fluid retention; limit processed foods, canned goods, salty snacks.

· Trans fats – partially hydrogenated oils; pro‑inflammatory.

· Saturated fats – excess intake promotes inflammation; limit coconut oil, palm oil, butter, cream, cheese.

· Alcohol – may interfere with methotrexate metabolism, exacerbate hepatotoxicity; limit or avoid.

· Smoking – single most important modifiable risk factor for AS severity. Cessation improves outcomes, reduces radiographic progression, and lowers cardiovascular risk.

Specific dietary considerations in SpA:

· Gluten: Only restrict if coexistent coeliac disease (more common in autoimmune disease) or documented non‑coeliac gluten sensitivity. Empirical gluten‑free diet in all AS is not evidence‑based.

· Nightshades (tomatoes, potatoes, peppers, eggplants): Anecdotal reports of symptom worsening; no scientific evidence. Individualised trial may be considered under supervision.

Lifestyle factors with proven benefit in SpA:

· Regular exercise:

· Essential for AS. Maintains spinal mobility, reduces stiffness, improves posture, and slows functional decline.

· Recommended: Daily stretching, spinal extension exercises, deep breathing, swimming, low‑impact aerobic activities.

· Physiotherapy / occupational therapy assessment is invaluable.

· Posture training:

· Avoiding prolonged flexion; sleeping on a firm mattress with a thin pillow.

· Stress reduction:

· Mindfulness, meditation, yoga, adequate sleep – stress exacerbates disease activity.

· Smoking cessation: As above.

· Weight management:

· Obesity worsens disease activity, reduces response to biologics, and increases cardiovascular risk.

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6. How soon can one expect improvement and the ideal time frame to retest

HLA‑B27 is a genetic test. It is performed once in a lifetime and never repeated.

Indications for (re)testing:

· None. If the result is negative but clinical suspicion remains high, repeat testing with a different method (e.g., PCR if flow cytometry was used) may be considered if the initial test was technically inadequate. This is not a repeat of the same test but a more definitive method.

Timeframe for improvement of spondyloarthritis with therapy:

· NSAIDs: Days.

· TNF inhibitors / IL‑17 inhibitors: 2–12 weeks (often dramatic improvement in pain and stiffness).

· Sulfasalazine (peripheral arthritis): 4–12 weeks.

· Methotrexate (peripheral PsA): 6–12 weeks.

Retesting disease activity markers:

· Clinical assessment (BASDAI, BASFI, ASDAS, swollen/tender joint counts, enthesitis scores): Every 1–3 months in active disease; every 3–6 months in stable remission.

· Acute phase reactants (CRP, ESR): Not elevated in all AS patients; useful when elevated at baseline, monitor every 3–6 months.

· Imaging (MRI sacroiliac joints, spine): As clinically indicated, not routinely repeated.

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Conclusion

HLA‑B27 is a genetic witness, not a dynamic biomarker. Its presence or absence is inscribed in every nucleated cell of the body, immutable from conception to death. For the rheumatologist, it is a powerful arrow in the diagnostic quiver – but it is not the arrow that hits the target.

A positive HLA‑B27 does not condemn a person to spondyloarthritis; it merely raises the index of suspicion. The diagnosis rests on the marriage of clinical symptoms, physical examination, imaging, and laboratory evidence of inflammation. And when the diagnosis is made, the treatment targets the inflammation, not the allele.

There is no cure for ankylosing spondylitis or its allied diseases, but there are highly effective therapies that can suppress inflammation, relieve pain, preserve mobility, and prevent disability. Biologics have transformed the prognosis of AS. Exercise and physical therapy remain indispensable.

A plant‑based, ecologically responsible diet – rich in legumes, whole grains, nuts, seeds, and algae‑derived omega‑3s – provides the anti‑inflammatory nutritional foundation that supports patients with spondyloarthritis. It supplies the calcium and vitamin D to protect bones rendered fragile by chronic inflammation, the fibre to nourish a healthy gut microbiome, and the antioxidants to combat oxidative stress. It reduces cardiovascular risk and aligns the care of the individual with the care of the planet. There is no requirement for meat; its displacement by plants is itself a therapeutic and ecological act.

HLA‑B27 is a single letter and number – B27. The patient is a story of back pain, stiffness, fatigue, and resilience. Listen to the patient, not the allele – but when the allele is present and the story fits, act swiftly and decisively.

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Note on dietary recommendations on this site:

For the sake of our environment we adhere to the following dietary preference hierarchy:

1. Plant‑based

2. Fungi / algae / fermented

3. Biotechnology / lab‑grown / cultures

4. Dairy / eggs

5. Meat / fish / poultry (only if no effective alternative exists)

Special note on bone health:

Patients with ankylosing spondylitis are at increased risk of osteoporosis and vertebral fractures. Ensure adequate calcium intake from plant sources (fortified plant milks, calcium‑set tofu, tahini, leafy greens) and vitamin D from lichen‑based supplements. Weight‑bearing exercise should be tailored to spinal mobility.

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