Session 7 Autoimmunity.pdf

Dr Leriska Haupt AUTOIMMUNITY Haematologist Dept of Haematology and Cell Biology T: 051 401 9111 i...

Dr Leriska Haupt AUTOIMMUNITY Haematologist Dept of Haematology and Cell Biology T: 051 401 9111 [email protected] www.ufs.ac.za  CONTENT PART 1: Autoimmunity Definitions: tolerance, autoimmunity, molecular mimicry Pathogenesis Classification PART 2: Ocular autoimmune conditions PART 3: Systemic autoimmune conditions Ocular manifestations T: 051 401 9111 [email protected] www.ufs.ac.za TOLERANCE We produce T- and B-cells that react against our own antigens. The body has mechanisms for removing these self-reactive T- and B-cells. – Mechanism for preventing autoimmunity Central tolerance: – Self-reacting lymphocytes are deleted (undergo cell death). – Induced in early stages of lymphocyte development (in thymus or bone marrow). Peripheral tolerance: – “Safety net” for getting rid of self-reactive lymphocytes that have escaped central tolerance. – Induced in mature lymphocytes. – Example: T-regulatory cells (Tregs) are suppress autoreactions WHAT IS AUTOIMMUNITY? A misdirected immune response that occurs when the immune system goes awry and attacks the body itself. Hypersensitivity reactions triggered by self-antigens MOLECULAR MIMICRY Foreign antigen initiates an immune response T- or B-cell component cross-recognizes self-antigens Cross-reactive immune response leads to an autoimmune disease  HLA subtype Immune system regulation Abnormal regulation of immune response: - T regulatory cells - Response to infectious agents, etc. Molecular mimicry CLASSIFICATION OF AUTOIMMUNE CONDITIONS Classified similarly to hypersensitivity reactions – Exception: there is no type I hypersensitivity AUTOIMMUNE CONDITIONS Antibody- Immune-complex Cell-mediated mediated (Type II) mediated (Type III) (Type IV) ANTIBODY-MEDIATED (TYPE II) HYPERSENSITIVITY REACTION Antibody reactive to self-antigen, binds to tissue/cells Example: autoimmune haemolytic anaemia Results in: Opsonisation – IgG antibodies bind to red cells – Phagocytosed by macrophages in spleen Compliment activation – IgM antibodies bind to red cells – Activate complement system – Intravascular lysis of red cells IMMUNE-COMPLEX MEDIATED (TYPE III) HYPERSENSITIVITY REACTION Immune complexes are usually cleared rapidly – If not cleared, this leads to inflammation Example: systemic lupus erythematosus (SLE) – Immune-complexes are deposited in tissues, which leads to dysfunction (e.g. renal failure, skin lesion, etc.) CELL-MEDIATED (TYPE IV) HYPERSENSITIVITY REACTION Autoimmune T-cell responses – T-helper and cytotoxic T-cells Example: rheumatoid arthritis – Inflammation and destruction of joints Example: type I diabetes mellitus – Destruction of insulin producing cells in pancreas. OCULAR AUTOIMMUNE DISEASES MOOREN’S ULCER Presentation Rare disorder Typically seen in healthy, adult men No evidence of systemic disease Painful, relentless, chronic ulcerative keratitis – Begins peripherally and progresses circumferentially and centrally Can lead to progressive destruction of the cornea MOOREN’S ULCER Etiology Unsure Possible autoimmune reactions: – Exposure to infectious agent (e.g. hepatitis C), and cross-reaction of epitope with ocular epitopes (molecular mimicry) Or – Deposition of immune complexes in limbal or peripheral corneal tissues, which leads to an immune response and tissue damage SYMPATHETIC OPHTHALMIA Emergency! Bilateral granulomatous uveitis that occurs after a penetrating injury to one eye. Very rare, but potentially blinding disease that involves both eyes. Less frequent since the use of microsurgery techniques – More frequently following nonsurgical trauma (0.2-0.5% of injuries) More common in men → higher incidence of ocular trauma Possible association with HLA-A11 SYMPATHETIC OPHTHALMIA Predisposing factors Penetrating injury (almost always occurs after a penetrating injury). Ciliary region wounds = dangerous zone – Any injury here predisposes the person to sympathetic endopthalmitis. Wounds with incarceration of the ciliary body, iris, lens capsule are vulnerable. More common in children than in adults Pathogenesis There are many theories "Allergic theory“: – Uveal pigment antigens act as an allergen – Lead to uveitis in the normal eye SYMPATHETIC OPHTHALMIA Presentation Occur between 2 weeks and 3 months following an ocular injury Moderate to severe vitritis Multiple white-yellow lesions in the periphery Retinal involvement +- subretinal neovascularisation SYSTEMIC AUTOIMMUNE DISEASES KERATOCONJUNCTIVITIS SICCA Dry eye syndrome Symptoms – More prominent during the latter part of the day because of the evaporation of the tear film. – Corneal examination (slit lamp) may reveal punctate erosive keratopathy or filaments.  Scleritis SCLERITIS OR EPISCLERITIS RA is the most common cause of scleritis (18-33% of cases) Scleritis and episcleritis are distinguished on the basis of anatomy and appearance Symptoms may be similar Scleritis – Pain evident and severe Episcleritis – Tenderness to palpation of the globe Patients with scleritis (not episcleritis) and RA – More widespread disease and worse prognosis  SCLERITIS VS EPISCLERITIS Scleritis Episcleritis 1-2 drops topical phenylephrine (2.5%) (Neo-Synephrine) Engorged vessels blanch in episcleritis Vessels remain dilated in scleritis  Rheumatoid Myasthenia arthritis gravis (see session 6) Sjögren’s Graves’ syndrome disease Diabetes Systemic mellitus autoimmune SLE (type I) diseases DIABETES MELLITUS (TYPE 1) Autoimmune condition where the insulin producing cells in pancreas are destroyed. – Leads to elevated blood glucose levels. – Damages the blood vessels in most organ systems (heart, kidney, etc.) including the eye. Cell-mediated (type IV) hypersensitivity. Ocular complications: – Diabetic retinopathy – Cataract formation – Glaucoma Prevention of complications: – Control of blood sugar levels – Regular eye exams SJÖGREN’S SYNDROME Autoimmune condition characterised by dry eyes and a dry mouth: – Mucous membranes and moisture-secreting glands of eyes and mouth are affected first. – Results in decreased production of tears and saliva. – Ocular manifestation: keratoconjunctivitis sicca More common in: – Women – >40 years Treatment is symptomatic. RHEUMATOID ARTHRITIS (RA) Chronic inflammatory disorder primarily affecting the joints, but can also affect the skin, eyes, lungs, heart and blood vessels. Cell-mediated (type IV) hypersensitivity. Approximately 25% of patients with (RA) will have ocular manifestations. – Keratoconjunctivitis sicca (most common, up to 25% of patients). – Scleritis/episcleritis (4-10% of patients with RA). – Keratitis – Peripheral corneal ulceration, etc. GRAVES’ DISEASE Autoimmune condition resulting in hyperthyroidism (overproduction of thyroid hormones). Inflammation and congestion of periocular and orbital soft tissue – Ocular manifestation: Graves’ ophthalmopathy (see below) – Other complications include exposure keratopathy, diplopia, compressive optic neuropathy More common in: – Women – 90% of SLE cases: women of childbearing age. Ocular disease occurs in 20% of SLE patients External ocular manifestations – Keratoconjunctivitis sicca – Conjunctivitis – Uveitis – Episcleritis and scleritis – Keratitis – Discoid lupus rash over the eyelids Intraocular manifestations – Microinfarction, haemorrhage, or vasculitis in various locations – Optic neuritis / optic neuropathy QUESTIONS OR COMMENTS? T: 051 401 9111 [email protected] www.ufs.ac.za