- The HLA-B27 Variant, Genetic Test & Autoimmunity
- The HLA System
- HLA-B27 Antigen
- HLA-B27 and Autoimmune Diseases
- Ankylosing Spondylitis (AS)
- The Connection
- Who Should Test?
- Genetic Variants
- Other tests
- Other Factors
- Microbiome and Infections
- Recommendations to Balance the Immune System
- Additional Resources
- Association of HLA-B27 and Behcet’s disease: a systematic review and meta-analysis
- HLA-B27: How to check your genetic data
- What is the HLA system?
- What is ankylosing spondylitis (AS)?
- Why is HLA-B27 linked to autoimmune diseases?
- Genetic Variants:
- Related Genes and Topics:
- Genetic Marker HLA-B27 Correlates With Ankylosing Spondylitis Onset but Not Disease Burden, Study Shows
- HLA-B27 Syndromes: Overview, Pathophysiology, Clinical Features of HLA-B27 Syndromes – Acute Anterior Uveitis
The HLA-B27 Variant, Genetic Test & Autoimmunity
The HLA-B27 gene variant has a strong connection with certain autoimmune disorders. Still, you can carry this variant and maintain flawless health. Read on to learn about HLA genes, the HLA-B27 variant, how it can be detected, and how it relates to autoimmunity. Finally, we share some tips to naturally balance the immune system and reduce inflammation.
We have a more personalized version of this blog post on SelfDecode; check it out here.
The HLA System
The human leukocyte antigen (HLA) system is a group of human genes encoding the major histocompatibility complex (MHC) proteins, or HLAs. This system has three groups or classes; HLA-B genes, along with HLA-A and HLA-C, belong to the class I .
HLAs are proteins or antigens on the surface of white blood cells. They help flag and remove external components that may cause infection. HLA-B antigens bring bacterial or viral proteins from the inside to the cell surface so T-lymphocytes can detect and kill the infected cell .
They also have anti-cancer effects and play a role in organ transplant rejection [3, 1].
HLA genes come in many different forms or variants, which enable the fine-tuning of your immune system. Their diversity can be a double-edged sword, however, as some types increase the risk of autoimmune disorders .
The HLA-B27 antigen supports antiviral immune response by “flagging” peptides from viruses – such as influenza, HIV, and Epstein-Barr – and presenting them to T-killer cells .
The gene for HLA-B27 has over 100 variations. Despite the beneficial roles, HLA-B27 is strongly associated with a group of autoimmune joint disorders known as spondyloarthritis (SpA) [6, 7].
The most common variations associated with autoimmunity are :
- HLA-B*27:05 (Caucasians/whites)
- HLA-B*27:04 (Chinese)
- HLA-B*27:02 (Mediterranean)
On the other hand, HLA-B*27:06 seems to have a protective role .
The prevalence of HLA-B27 varies from 50% in some Indian populations to almost zero in Australian Aborigines. About 6% of the US population carries this variant, which is more common among white people .
HLA-B27 and Autoimmune Diseases
It’s important to note that just because certain genotypes are associated with a disease, it doesn’t necessarily mean that everyone with that genotype will actually develop the disease! Many different factors, including other genetic and environmental factors, can influence the risk of autoimmune diseases.
Ankylosing Spondylitis (AS)
As mentioned, HLA-B27 strongly correlates with higher rates of certain autoimmune diseases, such as :
- Ankylosing spondylitis (spine deformation)
- IBD (inflammatory bowel disease), in combination with spondylitis
- Reactive arthritis (Reiter’s syndrome) – inflammation of joints, urethra, and eyes
These conditions have a common name spondyloarthritis, the main one being ankylosing spondylitis (AS). In AS, inflammation gradually fuses spine vertebrae, causing back pain and limited movement. It usually affects young men [12, 13].
Doctors treat AS with drugs such as NSAIDs and TNF-inhibitors, but their effectiveness is limited. Besides HLA-B27, other genetic and environmental factors are involved [14, 15, 2].
The connection between HLA-B27 and ankylosing spondylitis (AS) is among the strongest in the HLA system: 90–95% of all AS patients have this variant. For other conditions, the prevalence ranges between 50-90% .
Does this mean almost everyone with HLA-B27 will get AS or another autoimmune disease? Not at all!
Approximately 1.3% of European HLA-B27 carriers have AS, though Caucasian (white) ethnicity and the presence of a family member with AS increase the chance 16-20 times [16, 17].
Over 50% of people with anterior uveitis (eye inflammation) have this variant, but only 1% of all HLA-B27 carriers develop uveitis .
In other words, HLA-B27 is involved in the above disorders, but many more factors contribute and decide which carriers will get them.
Despite the well-known connection, the role of HLA-B27 in autoimmunity is still not fully clear. According to the main theories, the error probably occurs in [19, 20, 21, 5]:
- The way it binds and presents peptides to T-killer cells: upon activation, T-killer cells can mistakenly flag all HLA-B27 fragments as foreign peptides and attack them
- The biochemical properties (structure) of HLA-B27 itself: it can misfold in such a way that causes intracellular inflammation and triggers an immune response
Whatever the root cause, inflammation is the chief mechanism behind these autoimmune disorders .
Who Should Test?
You may want to do an HLA-B27 test if you [23, 24]:
- Have chronic pain, stiffness, and inflammation in your joints
- Have painful eye inflammation (uveitis)
- The above symptoms began in your early adulthood (the 20s or 30s)
Additionally, your doctor will order HLA tests if you’re undergoing organ or tissue transplantation .
The following genetic variants (SNPs) can help determine the chance you’re carrying HLA-B27 [26, 27, 15, 28, 29]:
- rs4349859 ( “A” allele correlates with HLA-B27, “G” doesn’t)
- rs13202464 (“G” allele correlates with HLA-B27, “A” doesn’t)
- rs116488202 (“T” allele correlates with HLA-B27, “C” doesn’t)
Carrying two alleles of HLA-B27 (homozygosity) doesn’t correlate more strongly with autoimmune diseases, compared with one allele .
Please note: To confirm the presence of this variant and detect the exact subtype, you may want to do the HLA-B27 blood test.
The following tests and lab markers can help detect inflammation and diagnose an autoimmune disease [30, 31, 32, 33]:
As mentioned, HLA-B27 is just a link in the chain of factors that can contribute to spondyloarthritis; scientists have discovered other genes and triggers.
Besides the major player, HLA-B27, other HLA variants may correlate with ankylosing spondylitis; these include HLA-B60 and HLA-DR1 [34, 35].
Variations in non-HLA genes associated with ankylosing spondylitis include [36, 37, 38, 39, 40]:
We have compiled a list of genetic traits associated with ankylosing spondylitis.
Microbiome and Infections
A solid body of evidence voices the role of the microbiome in spondyloarthritis [41, 42, 43].
Microbial infections can trigger autoimmune disorders by disturbing the gut probiotics, the guardians of your immunity. Reactive arthritis (previously known as Reiter’s syndrome) is associated with the following infections [44, 45, 46]:
Klebsiella infection is a crucial trigger of autoimmune joint and gut disorders, especially in HLA-B27 carriers [47, 48].
Other factors that may contribute to autoimmune diseases include:
- C-section delivery 
- Antibiotics [50, 51]
- Environmental toxins 
- Sleep deprivation [53, 54]
- Stress 
Recommendations to Balance the Immune System
Please note: none of the approaches listed below are meant to prevent or treat an autoimmune disorder, and they must not be used in place of medical treatment. If you have a diagnosed condition, make sure to consult with your doctor to see if you could add these to your treatment protocol.
Given the role of the microbiome and bacterial infections in autoimmunity triggered by HLA-B27, make sure to boost your gut health by:
Klebsiella is one of the autoimmunity triggers, and it thrives on sugar and starch. To cut your risk of infection, reduce the intake of sweets and refined carbs [56, 57, 58].
Zinc and copper-rich foods such as organ meats, seafood, seeds, and cocoa will support your immune system, reduce inflammation, and improve gut health [59, 60, 61].
Intermittent or other types of fasting stimulate autophagy, which can help balance an overactive immune response [62, 63].
To keep inflammation in check and balance the immune system, try to:
The following supplements may help by supporting your immune system and reducing inflammation:
- Gut Health
Food irritants can have an important role in inflammation and autoimmune disorders. The Lectin Avoidance Diet has a powerful program to help you detect and eliminate foods that are pro-inflammatory for you (hint: it’s not just about lectins).
Association of HLA-B27 and Behcet’s disease: a systematic review and meta-analysis
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HLA-B27: How to check your genetic data
Our immune system does an awesome job (most of the time) of fighting off pathogenic bacteria and viruses. But to fight off these pathogens, the body needs to know that they are the bad guys. This is where the HLA system comes in.
This article covers background information on HLA-B27 and the genetic variants available in 23andMe or AncestryDNA data.
What is the HLA system?
Human leukocyte antigens (HLA) is the part of our immune system known as the major histocompatibility complex (MHC). The HLA genes code for the proteins that help our body determine what is a foreign invader that needs to be attacked and what is ‘self’.
There are many different HLA serotypes that people can have, giving us all slightly different strengths and weaknesses against microbial diseases. But along with attacking foreign invaders, a handful of HLA types also increase the susceptibility to autoimmune diseases, where the body attacks its own cells.
HLA-B27 is linked to susceptibility to inflammatory-related autoimmune diseases including:
- ankylosing spondylitis[ref]
- reactive arthritis
- inflammatory bowel disease[ref]
- acute anterior uveitis
post infectious syndrome for shigellosis, salmonella, and chlamydia is more common in HLA-B27 positive.
What is ankylosing spondylitis (AS)?
Ankylosing spondylitis is a chronic inflammatory disease that mainly affects the spine. It causes back pain and spinal stiffness, and the vertebrae can fuse together. This often occurs in young adults. More info can be found on the Spondylitis Association of America site. Carriers of HLA-B27 are at a 20-fold risk for the disease.
Why is HLA-B27 linked to autoimmune diseases?
There are multiple subtypes of HLA-B27, and the specific types associated with ankylosing spondylitis include HLA-B*2701, HLA-B*2702, HLA-B*2704, HLA-B*2705, and HLA-B*2707.
Not everyone who carries the HLA-B27 serotype will have ankylosing spondylitis, but over 95% of people with AS carry HLA-B27. Similarly, over 80% of people with reactive arthritis are HLA-B27 positive.
[ref] Therefore, the HLA-B27 serotype is a big risk factor for these autoimmune diseases, but it doesn’t cause the autoimmune disease by itself.
Instead, there are must be other factors – environmental, pathogens, gut microbiome, diet? – that are involved. [ref]
Everyone has multiple HLA serotypes that are essential for combating pathogens. So why is this HLA-B27 more ly to lead to autoimmune conditions?
At one point, researchers advanced a theory that HLA-B27 was similar to an infecting bacterial pathogen. The idea is called ‘molecular mimicry’ and the idea is that the immune system attacks ‘self’ thinking that it is a bacteria.
(Some nice videos explaining ankylosing spondylosis state that this is the reason for it…) The problem is that newer research shows that you can create AS in an animal model without the T-cells needed for attacking a pathogen, so there is uncertainty as to whether this is actually a cause of AS. [ref][ref]
Proteins in the body, including the HLA proteins, are made up of amino acids that join together and then fold up in a particular way. Researchers have found that HLA-B27 has a tendency to misfold.
The specific subtypes of HLA-B27 associated with autoimmune diseases are ones that are ly to be misfolded or unfolded, causing problems when they are formed in the endoplasmic reticulum (ER).
The misfoleded or unfolded proteins in the ER cause stress in that organelle, possibly causing inflammation due to an unfolded protein response mechanism.[ref]
Genetic variants included in 23 and Me data that code for HLA-B27 are listed below. These variants show if you are ly to carry an HLA-B27 type. There are several subtypes of HLA-B27 and not all of them cause a higher risk of inflammatory autoimmune diseases. A blood test is still needed to be 100% certain that you carry the HLA-B27 type associated with autoimmune diseases.
Check your genetic data for rs4349859 (23andMe v5 only; AncestryDNA):
- A/A: high lihood of carrying 2 copies of HLA-B27[ref][ref][ref]
- A/G: high lihood of carrying 1 copy of HLA-B27
- G/G: normal
Check your genetic data for rs13202464 (23andMe v4, v5; AncestryDNA):
- G/G: high lihood of carrying 2 copies of HLA-B27[ref][ref][ref]
- A/G: high lihood of carrying 1 copy of HLA-B27
- A/A: normal
Keep it in perspective:
Don’t freak out if you are a carrier of HLA-B27. In Caucasians, about 10% of people carry one copy, whereas only 1% of African populations carry HLA-B27.[ref]
If you want to get the blood test for HLA-B27 and you can’t get it through your doctor, you can order it on your own in the US. UltaLab Tests is one place that I use. There are other websites as well, so shop around for the best price.
Although HLA-B27 increases the risk of ankylosing spondylosis by 20-fold, it is still a rare disease with about 1 in 2000 people having it.[ref] If you have the HLA-B27 serotype, the lifetime absolute risk is about 6%.[ref] There are other genetic variants thought to be involved in the risk for ankylosing spondylosis, as well as environmental factors.[ref]
Interestingly, carriers of the HLA-B27 have a survival advantage for HIV and hepatitis C.[ref]
There is also a connection between HLA-B27 and changes to the gut microbiome.[ref] Spondylitis patients also showed changes in the gut microbiome with decreased F. prausnitzii and increased Bacteroides fragilis.[ref] You may want to get a gut microbiome test done to see if everything is in order down there.
If you carry the HLA-B27 type and also have reactive arthritis, there is an interesting tie to salmonella persistence or other microbial infections.
Animal studies show that Lactobacillus G/G probiotics may help with preventing recurrence of inflammatory bowel problems associated with HLA-B27.[ref] Although I couldn’t find a human clinical trial on it, if you are wanting to try a Lactobacillus G/G probiotic, Culturelle contains that strain.
Autoimmune Paleo (AIP) diet:
The link between diet and symptoms of reactive arthritis or ankylosing spondylitis isn’t clear.
A meta-study looked at a bunch of studies on the subject and found no statistical links with diet. But individuals report that diet can make a difference in their joint pain with certain foods making it worse.
So trying an elimination diet or the autoimmune protocol diet may be worthwhile.
Related Genes and Topics:
CTLA-4 – General Autoimmune Risk Factor
The CTLA4 gene codes for a protein that is important in the immune system. It acts as a checkpoint that can downregulate your immune system response. Genetic variants in the CTLA4 gene can increase your risk for several different autoimmune diseases.
Psoriasis is an autoimmune condition that causes dry, sometimes itchy patches of skin. It is caused by the immune system attacking your skin cells, speeding up the turnover of the cells. Genetics plays a role in your susceptibility
Originally published 07/2018. Updated 1/2020.
Author Information: Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.
Genetic Marker HLA-B27 Correlates With Ankylosing Spondylitis Onset but Not Disease Burden, Study Shows
The presence of a specific genetic marker called HLA-B27 in Caucasian ankylosing spondylitis patients is related to earlier disease onset and higher disease prevalence among family members, a study has found.
However, according to the research, being HLAB27-positive is not related to a higher burden of disease or uveitis (inflammation of the eye).
The study, “Influence of HLA-B27 on the Ankylosing Spondylitis phenotype: results from the REGISPONSER database,” was published in Arthritis Research & Therapy.
Axial spondyloarthritis (AxSpA) refers to a group of rheumatoid diseases characterized by the involvement of the axial skeleton, the part of the skeleton that consists of the bones of the head and torso.
Ankylosing spondylitis (AS) is the most common disease in this group of disorders and clinically presents with inflammatory back pain — but can also involve other sites.
The prevalence of AS is about 0.2-0.3%, depending on the geographical distribution of human leukocyte antigen B27 (HLA-B27), the main genetic factor related to disease development.
HLA-B27, a protein present on the surface of white blood cells, is known to contribute to immune system dysfunction. The presence of HLA-B27 is associated with certain autoimmune and immune-mediated diseases, including AS and juvenile rheumatoid arthritis. However, nearly 10-20% of patients with defined AS do not carry HLA-B27.
Prior studies have suggested a relationship between the presence of HLA-B27 and axial manifestations. But only a few studies have evaluated the role of HLA-B27 in defined AS patients, and many of them have reported conflicting results.
Researchers in this study assessed the influence of HLA-B27 on the clinical presentation of AS patients. The team reviewed data from the Spanish REGISPONSER database, which includes more than 1,000 AS patients.
Data from 1,235 patients (74.8% male) were analyzed. Among them, 1,029 (83%) were HLA-B27-positive.
Researchers evaluated a number of different parameters including demographics, clinical presentation, disease activity, and radiographic data with regard to HLA-B27 status. A statistical analysis was conducted to determine which variables were independently related to HLA-B27.
HLA-B27-positive patients showed higher family aggregation. This means that HLA-B27-positive patients are more ly to have family members who also have AS than those who are HLA-B27-negative.
HLA-B27-positive patients also had an earlier disease onset than those who are HLA-B27 negative.
“Disease duration was significantly higher in HLA-B27-positive AS patients than the other group. Given that disease duration is one of the main factors related to structural damage, the data reported here do not support a major role of HLA-B27 in the extension of the structural damage in defined AS patients,” the researchers noted.
Compared with HLA-B27-positive patients, HLA-B27-negative patients presented with statistically higher scores of disease activity as well as higher prevalence of arthritis, dactylitis (inflammation of a digit), and extra-articular manifestations — such as psoriasis and inflammatory bowel disease (IBD) — but not uveitis.
Using multivariate statistical analysis, which looks at the observation and analysis of more than one outcome variable, researchers discovered that family history, younger age at diagnosis, presence of peripheral arthritis, dactylitis, psoriasis, and IBD were the main variables independently related to the presence or absence of HLA-B27.
“This study confirms the previously reported association in AS patients between HLA-B27 and an earlier disease onset and greater family aggregation,” the researchers wrote.
“However, and interestingly, we do not support an association between HLA-B27 and the extent of axial structural damage, or a higher clinical burden of the disease,” they added. “On the other hand, the absence of HLA-B27 is related, in AS patients, to a higher frequency of peripheral arthritis, dactylitis, and extra-articular manifestations.”
HLA-B27 Syndromes: Overview, Pathophysiology, Clinical Features of HLA-B27 Syndromes – Acute Anterior Uveitis
HLA-B27 associated acute anterior uveitis (AAU) is the most frequent type of endogenous uveitis (see image below), accounting for 18-32% of all anterior uveitis cases in western countries and for 6-13% of all anterior uveitis cases in Asia.
The relatively lower frequency in Asia is related to the lower frequency of HLA-B27 found in this population. As mentioned, there are varying global patterns of HLA-B27 associated AAU that may be attributed to different genetic factors, such as HLA-B27 polymorphisms and non-MHC genes.
These geographic variations may also exist because of yet unidentified pathogenic environmental factors.
Acute anterior uveitis in ankylosing spondylitis. Courtesy of Paul Dieppe, BSc, MD, FRCP, FFPHM.
Studies indicate that HLA-B27 associated uveitis is a distinct entity characterized by a male predominance and frequent association with seronegative arthritic syndromes, such as ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and inflammatory bowel disease.
 The first episode of HLA-B27 associated AAU most commonly occurs in patients aged 20-40 years, whereas the age of onset of HLA-B27-negative AAU tends to occur a decade later. Of patients with AAU, 50-60% may be HLA-B27 positive.
It is generally a benign nongranulomatous unilateral disease presenting as a classic triad of pain, redness, and photophobia.
Corneal manifestations may include fine keratitic precipitates and fibrin on the endothelium. Corneal edema may result from endothelial compromise and decompensation.
Band keratopathy, an accumulation of calcium in the corneal epithelium, may be seen in chronic uveitis.
The anterior chamber shows cells and flare, which is a haze seen on slit lamp examination, reflecting protein accumulation in the anterior chamber due to the breakdown of the blood-aqueous barrier, and, in severe inflammation, fibrinous exudate in the anterior chamber may occlude the pupil, causing iris bombe as depicted below. This fibrin may be mistaken for endogenous endophthalmitis, cataract, or hypopyon. A hypopyon may be seen, and, rarely, even a spontaneous hyphema occurs as a result of severely dilated iris vessels.
Anterior chamber fibrin collection in ankylosing spondylitis. Courtesy of Paul Dieppe, BSc, MD, FRCP, FFPHM.
Pigment dispersion, pupillary miosis, and iris nodules may be noted, and synechiae, both anterior and posterior, can occur. Posterior segment involvement is relatively rare, but cystoid macular edema, disc edema, pars plana exudates, or choroiditis may be seen.
Intraocular pressure often is low, secondary to decreased aqueous production with inflammation of the ciliary body and trabecular meshwork.
 Intraocular pressure also may be high if inflammatory cells and debris clog the trabecular meshwork, particularly in patients with preexisting poor facility of outflow.
AAU generally runs a short course of a few days to weeks up to 3 months, with a tendency to recur in the same eye, especially in individuals who are HLA-B27 positive. Complications of AAU include cataract, glaucoma, hypotony, cystoid macular edema, and synechiae formation.
The prognosis of anterior uveitis associated with HLA-B27, either with or without systemic disease, is less favorable when compared with patients who are HLA-B27 negative with idiopathic anterior uveitis. Despite the potential for sequelae, the overall prognosis is good.
Classic AAU resolves completely when promptly and aggressively treated. Undertreated or misdiagnosed cases may progress to chronic iridocyclitis due to permanent damage of the blood-aqueous barrier.
A careful history and physical examination usually helps distinguish between the uveitic entities associated with systemic disease and HLA-B27 from those that are not associated with HLA-B27.
Disease entities causing AAU are varied and include traumatic iritis, postcataract extraction iritis, juvenile rheumatoid arthritis, herpetic infection (both herpes simplex and herpes zoster), syphilis, sarcoidosis, Fuchs heterochromic iridocyclitis, glaucomatocyclitic crisis, Behcet disease, and low-grade endophthalmitis. 
The role of HLA-B27 testing in patients with unilateral AAU is important in the differential diagnosis.
The lack of HLA-B27 antigen in unilateral AAU may be a clue for the clinician to search for other specific uveitis entities and other systemic diseases.
It also may be useful in determining the prognosis of AAU, as AAU associated with HLA-B27, even in the absence of systemic disease, is less favorable and more ly to recur when compared with that of patients who are HLA-B27 negative.
Medical management of AAU includes topical or systemic corticosteroids and topical cycloplegics. Periocular corticosteroid injections are extremely useful in acute, recalcitrant, or noncompliant cases, particularly when posterior segment involvement occurs.
Immunosuppressive therapy may be necessary in refractory cases or in those patients with corticosteroid-induced adverse effects.
The primary goal is to eliminate all cells, thereby minimizing complications including cataracts, cystoid macular edema, hypotony, synechiae formation, or glaucoma.
Cycloplegics help relieve photophobia, secondary to ciliary spasm, and prevent and break synechiae formation. In most cases, short-acting drops, such as 1% cyclopentolate hydrochloride or 1% tropicamide, are sufficient.
These allow pupillary motility and rapid recovery when discontinued. Longer acting cycloplegics, such as 5% homatropine, 0.25% scopolamine, and 1% atropine may also be useful.
If the uveitis is more severe, more frequent dosing of cycloplegics may be necessary.
Topical corticosteroids are the mainstay of uveitis therapy, but they should be used prudently owing to their adverse effects. The goal is to use the minimum amount necessary to control inflammation and to prevent complications.
Aggressive initial therapy may hasten recovery and limit the duration of therapy. Prednisolone acetate 1% given every hour is strongly recommended for acute presentations. Usually, 2-3 weeks at maximal frequency is all that is necessary to completely eliminate all cells.
Always discontinue corticosteroids by tapering the dose.
Corticosteroids may be administered by 4 routes, including topical, periocular, intraocular (intravitreal), and systemic. Topical therapy is used in anterior uveitis. The dosing varies from hourly to once daily.
Ointment form is available to those who cannot tolerate the preservative in the drops and may be particularly useful for a longer-acting bedtime dosage.
Occasionally, severe inflammation may not respond and may require periocular, intraocular, or systemic corticosteroids, especially if the posterior segment is involved. Periocular corticosteroids are usually given as depot injections in the sub-Tenon space.
Intravitreal corticosteroids by injection or by implantation of a sustained released device have been shown to be useful in the treatment of both chronic uveitis and uveitic cystoid macular edema.
These sustained devices are particularly promising in treating long-standing inflammation, as they can release medications for as long as several years after implantation.
This would allow reduction or elimination of systemic corticosteroids or immunosuppressive agents, thereby minimizing adverse effects related to treatment with these agents. As with any corticosteroid treatment, intraocular pressures should be monitored on a regular basis.
Systemic corticosteroids can be administered orally or intravenously. These are especially beneficial when the systemic disease requires therapy as well. It is important to discuss the adverse effects of corticosteroids with the patient and to have these monitored by the patient's primary care physician. Prednisone at 1 mg/kg/d is a useful starting dose.
More potent immunosuppression may be required in patients with vision-threatening inflammation interfering with activities of daily living, lack of response to corticosteroid treatment, and intolerance of corticosteroids. Patients taking 10 mg or more to control their symptoms may benefit from an antimetabolite as a safer long-term treatment.
Drugs used in these situations include azathioprine, mycophenolate mofetil, cyclophosphamide, chlorambucil, methotrexate, tacrolimus, and cyclosporine. These agents typically are used in posterior uveitis or panuveitis, but they occasionally can be required in severe fibrinous anterior uveitis associated with reactive arthritis or ankylosing spondylitis.
Cyclosporine is becoming increasingly useful as an adjunct to systemic corticosteroids. It may allow the physician to decrease or totally withdraw the corticosteroids once the remission is achieved. The usual dose is 2.5-5 mg/kg/d.
Careful monitoring of blood pressure and renal function is required.
Investigational therapies include a sustained-release device containing cyclosporin or the highly lipid-soluble steroid fluocinolone and monoclonal antibodies against the CD4 molecule.
Current therapies for uveitis remain nonspecific in their mode of action, and they have a number of adverse effects, as already mentioned. Owing to this, several therapies dealing with immunomodulation have been investigated.
Two promising treatments involve antitumor necrosis factor alpha (anti-TNF-alpha) and the use of HLA-B27 oral tolerance therapy. TNF-alpha has been shown to be a critical inflammatory instigator in the pathogenesis of various forms of uveitis, including AAU, in both animal studies and human experimental studies.
In view of this, investigations were carried out to examine the efficacy and safety of using anti-TNF-alpha in the treatment of various forms of uveitis with favorable results. Infliximab is a murine-human chimeric monoclonal antibody directed against human TNF-alpha.
It has been shown to be a rapid, effective, and safe therapy of vision-threatening ocular inflammation in Behcet disease and refractory posterior uveitis.
Etanercept is a genetically engineered fusion protein, which binds and inactivates both TNF-alpha and TNF-beta.
One study showed the efficacy of this protein in improving both ocular inflammation and articular inflammation when injected subcutaneously twice a week for at least 3 months in the treatment of resistant chronic uveitis, including chronic anterior uveitis in children with juvenile rheumatoid uveitis and idiopathic uveitis. This allowed the reduction of both systemic corticosteroids and/or systemic methotrexate.
Oral tolerance involves administering an antigen orally to induce a specific peripheral immune tolerance.
The mechanisms of oral tolerance are unclear, but it is believed that it involves a specific antigen and the generation of active suppression or clonal anergy dependent on the antigen dose.
Oral tolerance has been shown to be successful in experimental models dealing with multiple sclerosis, arthritis, diabetes, myasthenia gravis, and uveitis.
this, clinical studies have been initiated using such antigens as myelin in multiple sclerosis, collagen in rheumatoid arthritis, and uveitogenic peptides in intermediate and posterior uveitis, again with success and few adverse effects from the treatment. An HLA-B27-derived peptide (B27PD) mimicking retinal autoantigen has been found to be effective in both animal models and patients with uveitis.
Other emerging therapeutic options include antibiotic therapy in view of the implicated role of gram-negative bacterial infections on triggering HLA-B27 associated AAU.
Sulfasalazine treatment has been investigated for its potential role in reducing the number of recurrent attacks of AAU, and prophylactic ciprofloxacin has also been investigated but was not found to be beneficial in view of its adverse effects and cost.
Future novel potential treatments will a better understanding of the immune system and will include such substances as cytokines, chemokines, cell adhesion molecules, and T-cell subsets.
The role of the rheumatologist in the management of AAU is important in identifying underlying systemic diseases that may be present and in monitoring subsequent immunosuppressive therapy.
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