Autoimmune Diseases PDF

Autoimmune Diseases Dr Nouran Moustafa College of Medicine,DAU Objectives To know that the inflammatory processes in autoimmune diseases are mediated by hypersensitivity reactions (type II, III and IV). To know that autoimmune diseases can be either organ specific or may be gener...

Autoimmune Diseases Dr Nouran Moustafa College of Medicine,DAU Objectives To know that the inflammatory processes in autoimmune diseases are mediated by hypersensitivity reactions (type II, III and IV). To know that autoimmune diseases can be either organ specific or may be generalized involving many organs or tissues. To understand that the manifestations of autoimmune diseases depend upon the organ and the degree of damage inflicted on the target tissues. Autoimmune disease Autoimmune disease is tissue damage or disturbed physiological function due to an autoimmune response. Loading… More than 80 autoimmune diseases have been identified. Although relatively rare, they affect about 5% of the population in the developed world. Most of autoimmune diseases selectively affect women. Mechanism of Autoimmune Diseases Loss of self-tolerance leads to the production of auto-antibodies or a response by auto-reactive T cells against a person’s own tissue antigens. Autoimmune reactions, and the diseases they cause, can be: Cytotoxic (Type II hypersensitivity) Immune complex (Type III hypersensitivity) Cell-mediated (Type IV hypersensitivity)  Patterns of autoimmune diseases Organ-specific autoimmune disease The immune response is usually directed against self-antigens in one type of cell ,tissue or organs. Loading… Mostly affect one or another endocrine gland. E.g., Graves’ disease ,Myasthenia gravis  Non-organ-specific autoimmune disease Affect multiple organs (systemic disease) The immune response is usually directed against self- molecules that are widely distributed allover the body. E.g., systemic lupus erythematosus, rheumatoid arthritis Disease Target Type of Hypersensitivity Characteristics Antibodies against thyroid- Graves’ disease Thyroid II stimulating hormone receptors. Antibodies against the acetylcholine receptors on the Myasthenia gravis Muscle II nerve-muscle junction alter function. Inflammation of many organs; antibodies against red Systemic lupus Systemic III and white blood cells, erythematosus (SLE) platelets, clotting factors, nucleus DNA. Vasculitis; frequent target is joint lining; antibodies Rheumatoid arthritis Systemic III and IV against other antibodies (rheumatoid factor); T-cell cytokine damage. Diseases Involving Primarily One Type of Cell or Organ 1.Graves disease ( Thyrotoxicosis ) Cytotoxic autoimmune reaction Involve reactions of auto-antibodies called Thyroid stimulating immunoglobulins (TSIs) against thyroid stimulating hormone (TSH) receptors. Normally the thyroid gland receptors are stimulated by TSH, released from pituitary gland, to produce thyroid hormones. In Graves’ disease the thyroid gland is stimulated by TSIs that mimic TSH ,causing production of excessive amounts of thyroid hormones T3 and T4 (Hyperthyroidism). Clinical manifestations The most striking signs of the disease are: Loading… Goiter (a disfiguring swelling of the thyroid gland in the neck) Thyroid Goiter Exophthalmos ( Markedly bulging, staring eyes). Other signs includes heart palpitation, shivering , and sweating. Thyroid Ophthalmopathy Diagnosis: Detection of anti-TSH receptors antibodies in serum Treatment : Antithyroid drugs Immunesuppressive drugs e.g.corticosteroids Plasmapheresis 2. Myasthenia gravis Cytotoxic autoimmune reaction Caused by auto-antibodies that coat the acetylcholine receptors(ACHR) at the neuromuscular junctions. This leads to a reduction in the number of functional AChR by increasing degradation (complement mediated) of receptors. Eventually, the muscles fail to receive the necessary nerve signals.  Clinical manifestations Muscle weakness and fatigability on sustained effort. Respiratory arrest and death could occur due to affection of the respiratory muscles. Myasthenia gravis  Diagnosis: Detection of Anti-acetyl choline receptors(ACHR) antibodies in serum Treatment : Anti-choline esterase medicines Immunesuppressive drugs e.g.corticosteroids Plasmapheresis Diseases Involving Multiple Organs(systemic diseases)  Systemic Lupus Erythematosus Immune Complex Autoimmune Reaction One of the most severe chronic systemic autoimmune diseases that affects the skin of the face, the joints, and the kidneys. Affected individuals produce antinuclear antibodies(ANA abs) including auto-antibodies against DNA and other nucleoprotein of their own cells. ANA by Most of the clinical findings are caused by immune Immunofluorescence complexes deposition ,that activate complement and, as a consequence, damage tissue. SLE primarily affects women between the ages of 20 and 60 years. Clinical manifestations: Butterfly rash (characteristic rash on the cheeks is the result of a vasculitis). Arthritis, lung inflammation, myocarditis and glomerulonephritis commonly seen. Anemia, leukopenia, and thrombocytopenia. The most damaging effects of the disease result from deposits of immune complexes in the Butterfly rash kidney glomeruli. Diagnosis: Blood tests to detect: Antinuclear antibodies (ANAs) : determined by immunofluorescence ,common but not specific. Antidouble-stranded DNA (Anti –ds DNA) antibodies: are the hallmark of disease(more specific) Reduced level of complement. Treatment : NSAIDs (Non-steroidal anti-inflammatory Rheumatoid arthritis Immune Complex mediated Autoimmune Reaction Another systemic autoimmune disease, that leads to progressive, debilitating damage to the joints. The main clinical finding is inflammation of the proximal interphalangeal and metacarpophalangeal joints of the hands, the small joints of the feet, and the cervical spine, knees, and shoulders. Rheumatoid arthritis In some patients, the lungs, pericardium, eyes, skin, and nervous system are also involved.  RA affects primarily women between the ages of 30 and 50 years. The cause of rheumatoid arthritis is not known but may be related to : Genetic predisposition (e.g. HLA-DR4) Environmental triggers. Serum and synovial fluid of patients often contain rheumatoid factor. There is a lack of tolerance to citrullinated proteins and the appearance of autoantibodies directed against citrullinated proteins  Rheumatoid factor : is an antibody (usually IgM but occasionally IgG, IgD, IgA, or IgE) whose Fab recognizes and binds to the Fc fragment of normal human IgG. Despite its name ,Rheumatoid factor is associated with RA but is not specific for it. Rheumatoid factor Pathogenesis Caused by deposits of immune complexes (containing the normal IgG and rheumatoid factor) on synovial membranes and in blood vessels activating complement and attracting polymorphonuclear cells, causing inflammation. The synovial fluid contains high levels of macrophage-produced inflammatory cytokines such as TNF, IL-1, and IL-6. These cytokines (such as tumor necrosis factor [TNF]) can then trigger additional type IV delayed hypersensitivity responses. Diagnosis High titers of rheumatoid factor in serum and synovial fluid Anti–citrullinated protein (ACP) /anti-cyclic citrullinated protein(CCP) antibodies are specific markers. Low titers of complement in serum, especially during periods when the disease is most active. Treatment Typically involves aspirin, nonsteroidal anti-inflammatory drugs, immunosuppressive drugs (especially methotrexate), or corticosteroids TNF inhibitors :helpful in suppressing inflammation before it causes joint destruction and deformity. Other therapies as anti IL-1 and IL-6 are also used.