HLA association is one of the cause of uveitis.it is small part of a large topic.

1. HLA
Associated
Uveitis
Speaker:
DR. NAFIZ MAHMOOD
DO student , NIO&H

2. .
The term is commonly used to describe
many forms of intraocular inflammation
involving not only the uvea
but also the retina & its vessels.
Uveitis
Inflammation of the uveal tract

4. Major Histocompatibility Complex ( MHC) :
Cell surface glycoproteins responsible for regulation of
Immune system.
Human Leukocyte antigen ( HLA )
Cell surface glycoprotein encoded by HLA gene located on
chromosome 6, responsible for regulation
of Immune system in humans

5. At the end of the paper, Dausset wrote
that
‘Finally, in a more long time perspective,
the study of leucocyte antigens might
become of great importance in tissue
transplantation, in particular in bone
marrow transplantation’
(translated from French).
The credit for discovery of the first HLA antigen
goes to Dausset
Jean Dausset (1916–2009)

8. MHC class I
( HLA – A , B , C )
Surface of all nucleated cells
MHC class II
( HLA – DP , DQ , DR )
Antigen presenting cells (APC)
glycoproteins

9. Pathogenesis
A. HLA are peptide binding molecules for etiologic antigens
or infectious agents
Thus , specific HLA might be predisposed to process certain Ag
Such as an infectious agent cross-reacts with a self Ag
B. Molecular mimicry between infectious Ag & epitope of
HLA molecule
C. Mutation recognise self as non-self
immunologic reaction

10. Functions of MHC/ HLA
Defense
Transplant rejections
Protect against cancers
Associated with Autoimmune diseases

11. Diseases associated with HLA
HLA Diseases
A3 Haemochromatosis
B5 Behcet’s disease
B27 Ankylosing spondylitis
Reiter’s syndrome
Psoriatic arthritis
Acute anterior uveitis

12. Cont…
HLA Diseases
DR2 Multiple sclerosis
Pernicious anaemia
DR4 Type 1 DM
Rheumatoid arthritis
DR5 Pernicious anaemia
DR7 Coeliac disease

13. Cont…
HLA Diseases
DR3 Dermatitis herpetiformis
Coeliac disease
Sjogren syndrome
SLE
Addison’s disease
Grave’s disease
Hashimito’s thyroiditis
Myasthenia gravis
Type 1 DM

15. Uveitic diseases with HLA associations
Diseases HLA association
Tubulointestinal nephritis &
uveitis (TINU)syndrome
HLA- DRB1
Birdshot retinochoroidopathy HLA- A29
Reactive arthritis HLA- B27
Acute anterior uveitis HLA- B27
Strong association

16. Diseases HLA association
Juvenile idiopathic arthritis HLA- A2,DR5,DR8,DR11
Behcet disease HLA- B51
Intermediate uveitis HLA- B8,B51,DR2,DR15
Sympathetic ophthalmia HLA- DR4
Vogt-Koyanagi-Harada
Syndrome
HLA- DR4
Sarcoidosis HLA- B8,B13
Multiple sclerosis HLA- B7, DR2
Retinal vasculitis HLA- B44
Weaker association

17. Ankylosing spondylitis
Inflammation
calcification,
ossification of
ligament & capsules
of joints of
axial skeleton
Male
Presentation
• 3rd-4th decades
• Insidious onset-
Lower back pain & stiffness
Systemic features
• Progressive limitation of spinal movement
• Enthesitis
• Cardiac complications

18. Ocular features
o Acute anterior uveitis 25%
o Scleritis
o Episcleritis
o Keratitis
o Mechanical ptosis
Bony obliteration of sacroiliac joint
Bamboo spine

19. Reiter syndrome
Triad
• Non-gonococcal urethritis
• Conjunctivitis
• arthritis
Systemic features
Peripheral arthritis
Spondyloarthropathy
Enthesitis
Mucocutaneous lesions
Genitourinary involvement
Pathogenesis
1–3% after non-specific urethritis,
4% of persons after enteric infections
by
• Shigella,
• Salmonella and
• Campylobacter
• Yersinia
3rd–4th decades
Ocular fetures
• AAU – 12%
• conjunctivitis

20. keratoderma blenorrhagica in Reiter syndrome

21. Psoriatic arthritis
Male = Female 3rd–4th decades
Signs
A. Skin :
• Plaque psoriasis
• Flexure psoriasis
B. Nail dystrophy
C. Arthritis
Ocular features
AAU – 7%
conjunctivitis,
marginal corneal infiltrates

22. Juvenile idiopathic arthritis
Systemic onset:
Characterized by-
• Fever
• Rash
• Lymphadenopathy
• Hepatosplenomegay
** uveitis – less than 6%
polyarticular onset:
More than 4 joints
40% of all JIA
ANA + in 40%
** iridocyclitis – 10%
F:M – 3:1
pauciarticular onset:
4 joints or less
ANA + in 75%
** uveitis – 20%
F:M – 5:1
Complications
Band keratopathy
Cataract
Glaucoma
Vitreous debris
ME
Ch. Hypotony
phthisis

23. Inflammatory bowel disease
Ulcerative colitis
Intestinal menifestations
• bloody diarrhoea
• lower abdominal cramps
• urgency
• tenesmus
Extra-intestinal menifestation
• Muco-cutaneous lesions
• Arthritis
• Hepatic disease
• Thromboses
2nd–3rd decades
AAU – 12%
diffuse surface ulceration of the mucosa with
development of crypt abscesses
and pseudopolyps

24. pseudopolyposis, lack of haustration

25. Crohn disease
Intestinal menifestations
• diarrhoea
• abdominal pain.
Extra-intestinal menifestation
• Muco-cutaneous lesions
• Clubbing, arthritis
• sacroiliitis
• ankylosing spondylitis.
2nd–3rd decades
AAU – 3%
multifocal, full-thickness,
non-caseating granulomatous
inflammation of the intestinal wall

26. stricture in the descending colon

27. Birdshot retinochoidopathy
Idiopathic chronic bilateral
Middle aged women
Clinical feature
Symptoms
• Insidious impairment of central vision
• Photopsia
• Floaters
• Nyctalopia
• Disturbance of color vision
vitritis

28. Fundus
• Multifocal,hypopigmented,ovoid, cream-colored choroidal
lesions in post-equarorial region
• Emanate from optic nerve
• Radial distribution
CME
ERM
CNV

29. Investigations :
• HLA- A29 : sensitive 96% ; specific 93%
• OCT
• Autofluorescence
• FA
• ICGA
• ERG : rod & cone abnormalities
Treatment :
 Systemic & intraocular steroids
 Immunosuppresent

30. Vogt-Koyanagi-Harada syndrome
Idiopathic multisystem autoimmue disease
Affects:
• Uvea
• Ear
• Meninges
Pigmented individuals
HLA – DR1, DR4
Prodromal phase
Meningitis
Auditory menifestations
Tinnitus
Vertigo
Deafness
Cranial nerve palsies
Optic neuritis

31. Acute uveitic phase
Bilateral granulomatous AU
Multifocal posterior uveitis
Diffuse choroidal infiltration
Dalen-fuchs nodules
Vitritis
Papillitis
Exudative RD

32. Convalescent phase
Localized alopecia
Poliosis
Vitiligo
Sunset glow fundus
Depigmented limbal lesions
Chronic recurrent phase
Smouldering AU with exacerbation

33. Diagnostic criteria
1. Absence of a history of penetrating ocular trauma
2. Absence of other ocular disease entities
3. Bilateral uveitis
4. Neurological and auditory manifestations
5. Integumentary findings, not preceding onset of central
nervous system or ocular disease, such as alopecia, poliosis and
vitiligo
In complete VKH, criteria 1–5 must be present.
In incomplete VKH, criteria 1–3 and either 4 or 5 must be present.
In probable VKH (isolated ocular disease), criteria 1–3 must be present

34. Complications
• CNV
• Subretinal fibrosis
• Preretinal & disc new vessels
• Vitreous haemorrhage
• Cataract glaucoma
Investigations
Lumbar puncture
FAF
OCT
B-scan
FA
ICGA
Traetment
High dose (1-2mg/kg/day) oral prednisolone, tapered over 3-6
months
Preceeded by IV methylprednisolone(500-1000 mg/day)
Topical steroids, Cycloplegics,Immunosuppressives
Biological blockers

35. Idopathic multisystem syndrome
Behcet disease Male predominent
Diagnostic criteria
1. Recurrent oral ulceration ( at least 3 times in 12 months)
2. Plus at least two of the following:
• Recurrent genital ulceration
• Ocular inflammation.
• Skin lesions include erythema nodosum, folliculitis, acneiform
nodules or papulopustular lesions.
• Positive pathergy test - formation of a pustule after 24–48 hours
at the site of a sterile needle prick

36. Other systemic features
• Vascular lesions
• Arthritis
• Dermatographia
• Neurological menifestations
• Gastrointestinal inflammation
• Hepatic & renal lesions

37. Ocular features (75%)
 AAU – bilateral, granulomatous
 Vitritis
 Retinitis – transient superficial white infiltrate heal without
scarring
 Retinal vasculitis – sheathing, perivascular Hge,occlusion,CMO
 Optic disc hypermia & edema
 Uncommon – conjunctivitis, episcleritis, scleritis
ophthalmoplegia

38. End stage disease
• Optic atrophy
• Retinal atrophy
• Gliosis
• Sheathing
• Attinuation & ghosting of vessels

39. Investigation :
• HLA – B51
• Pathergy test
• Inflammatory markers
• Thrombophilia screening
• FA
• Superficial lesion biopsy
• Systemic imaging – MRI/MRA,CTA of brain,

40. Treatment
 Topical steroids
 Systemic steroids & azathioprine
 Ciclosporin
 Infliximab or adalimumab
 Interferon alfa
 Anticoagulants

41. Conclusion
Testing for HLA can provide supporting evidence
for a particular diagnosis,
but cannot make
definitive diagnosis.
Remember