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Autoimmunity- its Types and diagnosis.pdf
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- 2. Outline History Definition Disease states Causes Immunopathology Diagnosis Treatment
- 3. Autoimmunity Origins Horror autotoxicus: Literally,the horror of self-toxicity. A term coined by the German immunologist Paul Ehrlich (1854- 1915) to describe the body's innate aversion to immunological self- destruction.
- 4. History Continued This conceptof autoimmunity as the cause of human illness is relatively new, and it was not accepted into the mainstream of medical thinking until the 1950s and 1960s.
- 5. Autoimmunity Basically meansimmunity to self A condition that occurs when the immune system mistakenly attacks and destroys healthy body tissue.
- 6. The “Immunology Definition” Failureof immune tolerance
- 8. Pick an organ,any organ . . . Autoimmunity can affect ANY organ/organ system in the human body Pemphigus Multiple Sclerosis Sjogren’s Syndrome Rheumatic Fever Autoimmune Hepatitis Ulcerative Colitis Goodpasture’s Syndrome Autoimmune Uveitis Autoimmune hemolytic Anemia Diabetes Addison’s Disease Rheumatoid Arthritis Autoimmune Oophoritis
- 11. Types of autoimmunediseases There are more than 100 different autoimmune diseases. They can affect almost any tissue or organ in your body, depending on where your immune system malfunctions, including your: •Joints. •Muscles. •Skin. •Blood vessels. •Digestive system. •Endocrine system. •Nervous system.
- 12. Joints and muscles •Rheumatoidarthritis (RA). •Lupus. •Myositis. Skin and blood vessels •Sjögren’s syndrome. •Psoriasis. •Psoriatic arthritis. •Dermatomyositis. •Scleroderma. •Vasculitis. •Rheumatoid vasculitis. •Urticarial vasculitis. •Vitiligo.
- 13. Nervous system •Multiple sclerosis (MS). •Myastheniagravis (MG). •Guillain-Barré syndrome. •Chronic inflammatory demyelinating polyneuropathy (CIPD). Digestive system •Crohn’s disease. •Celiac disease. •Ulcerative colitis. •Autoimmune gastritis. Endocrine system •Type 1 diabetes. •Addison’s disease. •Hashimoto’s • thyroiditis. •Graves’ disease.
- 14. Autoimmunity Classification Can beclassified into clusters that are either organ-specific or systemic
- 15. Hemolytic Auto immunedisease Organ specific Autoimmune disease Systemic Autoimmune disease Classification of Autoimmune diseases
- 16. Hemolytic Auto immunedisease Auto immune Haemolytic Anaemia Autoimmune Thrombocytopenia Auto immune Leucopenia Classification of Autoimmune diseases
- 17. Classification of Autoimmunity Organ specific Autoimmune disease Thyroid- Hashimoto’s disease,(goitre) Thyotoxicosis( Graves’ Disease) Adrenal gland- Addisons disease Testes- Autoimmune Orchitis Muscles- Myasthenia gravis Eye- Phacoanaphylaxis, Symphatetic Ophthalmia GI Tract- Pernicious anaemia Nervous system- Idiopathic polyneuritis ( Guillian barre Syndrome) Skin- Bullous pemphigous, Pemphigus vulgaris, Dermatitis herpetiformis Classification of Autoimmune diseases
- 18. Systemic Autoimmune disease Systemiclupus erythematosus Rheumatoid arthritis Polyarteritis nodosa Sjogrens syndrome Classification of Autoimmune diseases
- 19. Examples of OrganSpecific Lungs of a patient with Goodpasture’s Vitiligo Hashimoto’s disease (thyroiditis)
- 20. Examples of SystemicAutoimmunity SLE
- 21. Examples of SystemicAutoimmunity Sjogren’s Syndrome
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- 24. Infections- COVID-19 andEBV, S. pyogenes •Your sex. Women are more likely to have autoimmune conditions. •.genetic conditions and pass through generations of a biological family. •environmental factors- Exposure to chemicals, certain kinds of pollution or other might trigger autoimmune diseases. •Drug induced anaemia, leucopenia and thrombocytopenia •Smoking and using other types of tobacco can cause many health issues, including potentially triggering autoimmune diseases. Causes of auto immunity
- 25. Infectious basis COVID-19 individualswho contract COVID-19 may have a higher likelihood of developing conditions like vasculitis, alopecia, vitiligo, Crohn's disease, ulcerative colitis, and rheumatoid arthritis. and Epstein-Barr virus.( infectious mononucleosis) The Epstein-Barr virus (EBV), a common herpesvirus, is implicated in the development and progression of various autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS).
- 26. Infectious basis Streptococcus pyogenes Poststreptococcal sequelae- M protein and Heart muscle Nephritogenic strain and Renal glomeruli Molecular mimicry Homologous sequences Shigella flexneri & HLA B 27 Mycobacterium tuberculosis and Joint membrane Coxsackie B and myocardium
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- 28. Rheumatic fever is a classic exampleof molecular mimicry
- 29. Hormones Females aremuch more likely to develop autoimmune illness Rise in hormones associated with pregnancy may even cause abortion of the fetus (RSA) Endometriosis and preeclampsia are both thought to be autoimmune in nature Hypothesis: estrogen response elements (EREs) in several genes
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- 31. Nature Immunology 2,777 - 780 (2001) Sex differences in autoimmunity
- 32. Genes and Autoimmunity The concept that a single gene mutation leads to a single autoimmune disease is the EXCEPTION not the rule. Because of this autoimmune diseases are generally classified as complex diseases as there is not a single “pinpoint-able” gene
- 33. Exceptions to theRule – Simple Genetic Autoimmune Illnesses Disease Gene Mechanism APS-1 (Autoimmune polyglandular syndrome type 1) AIRE Decreased expression of self-antigens in the thymus, resulting is a defect in negative selection IPEX (Immunodysregulation, polyendocrinopathy, enteropathy, X-linked) FOXP3 Decreased generation of Tregs ALPS (autoimmune lymphoproliferative syndrome ) FAS, FASL Failure of apoptotic death of self reactive T or B cells
- 34. Complex Disease andGenetics There have been numerous disease associated genes or disease “susceptibility” genes linked to autoimmunity
- 35. Environment Pathogens, drugs,hormones, and toxins are just a few ways that the environment can trigger autoimmunity
- 36. Drugs Procainamide (Pronestyl-Drug induced lupus Chemicals- 2 mercapto ethanol Bacterial products- PPD, LPS Enzymes- Trypsin Antibiotics- nystatin Mycoplasma pneumonia- anti human erythrocyte cold antibody Infectious mononucleosis- anti sheep erythrocyte anti bodies Polyclonal B cell activation- IgM antibodies
- 37. Complement Deficiencies CD59or CD55 – Paroxysmal nocturnal hemoglobinuria autoimmune hemolytic anemia autoimmune thrombocytopenia lupus lymphopenia Deficiencies in the classical complement pathway renders pts more likely to develop immune complex diseases SLE RA
- 38. The Complement See-Saw The complement system is a mediator in both the pathogenesis and prevention of immune complex diseases It has a protective effect when functioning in moderation against pathogens; at the same time, the inflammation promoted by complement activation can result in cellular damage when not kept in check.
- 39. B or T?That is the question? Autoimmunity is hard to classify as strictly a B cell or T cell mediated disease as multiple arms of the immune system are involved Classification of Auto immunity
- 40. Hemolytic Auto immunedisease Auto immune Haemolytic Anaemia - Cold( IgM) & warm (IgG) abs -Direct Coombs test Autoimmune Thrombocytopenia AB mediated Hypersensitivity- drug Auto immune Leucopenia SLE and RA
- 41. Classification of Autoimmunity Organ specific Autoimmune disease Thyroid- Hashimoto’s disease,(goitre) Thyotoxicosis( Graves’ Disease) Adrenal gland- Addisons disease Testes- Autoimmune Orchitis Muscles- Myasthenia gravis Eye- Phacoanaphylaxis, Symphatetic Ophthalmia GI Tract- Pernicious anaemia Nervous system- Idiopathic polyneuritis ( Guillian barre Syndrome) Multiple sclerosis Skin- Bullous pemphigous, Pemphigus vulgaris, Dermatitis herpetiformis Classification of Autoimmune diseases
- 42. Thyroid- Hashimoto’s disease,(goitre) Anti Throglobulinantibody Enlargement of thyroid gland- Hypothroidism- Symptoms Fatigue, weight gain, intolerance to cold, constipation, dry skin, hair loss, and difficulty concentrating. Thyotoxicosis( Graves’ Disease) IgG ab to Thyroid membrane antigen Hyper thyroidism Symptoms Rapid heartbeat, weight loss despite increased appetite, anxiety, nervousness, heat intolerance, insomnia, and sometimes an enlarged thyroid gland
- 43. GI tract Crohn’s disease Celiacdisease is an illness caused by an immune reaction to eating gluten. Gluten is a protein found in foods containing wheat, barley or rye. Inflammation stomach and Large intestine Symptoms •Diarrhea. •Fatigue. •Weight loss. •Bloating and gas. •Abdominal pain. •Nausea and vomiting. •Constipation.
- 44. GI tract Celiac disease Infklammationstomach and Large intestine Symptoms •Abdominal pain and cramping. •Diarrhea. •Fever. •Fatigue. •Weight loss. •Loss of appetite. •Rectal bleeding. •Other potential complications include intestinal obstruction, fistulas, abscesses, and malnutrition.
- 45. Myasthenia Gravis Disease markedby progressive weakness and loss of muscle control Classified as a “B cell” Disease Autoantibodies against nicotinic acetylcholine receptors
- 46. Multiple Sclerosis MS patientscan have autoantibodies and/or self reactive T cells which are responsible for the demyelination
- 47. Multiple Sclerosis MS patientscan have autoantibodies and/or self reactive T cells which are responsible for the demyelination vision problems, difficulty walking or keeping balance, numbness or weakness in limbs, fatigue, and cognitive difficulties. Symptoms There are no specific tests for MS. The diagnosis is given by a combination of medical history, physical exam, MRIs and spinal tap results. Diagnosis
- 48. Diabetes Disease in which thebody does not produce or properly use insulin “ T cell” Disease T cells attack and destroy pancreatic beta cells
- 49. Systemic Autoimmune disease Systemiclupus erythematosus Rheumatoid arthritis Polyarteritis nodosa Sjogrens syndrome Classification of Autoimmune diseases
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- 51. Symptoms joint pain andswelling, fatigue, skin rashes (like the butterfly rash), fever, and hair loss. Systemic lupus Erythematosus Common Symptoms: Joint Pain and Swelling: SLE can cause inflammation in the joints, leading to pain, stiffness, and swelling. Joint involvement is often symmetrical and can affect multiple joints. Skin Rashes: A characteristic butterfly rash across the cheeks and nose is common, but rashes can appear elsewhere on the body. Fatigue:, Fever:, Hair Loss: Mouth Sores: Ulcers in the mouth or nose can be present. Sensitivity to Sunlight: Skin lesions can worsen with sun exposure. Raynaud's Phenomenon: Fingers and toes may turn white or blue when exposed to cold. Swollen Lymph Nodes: Enlarged lymph nodes are common, especially in children and young adults.
- 52. Other Symptoms: Weight loss,chest pain when breathing deeply, swollen legs or around the eyes, and headaches can also occur. The Brain and Nervous System: Headaches, cognitive impairment, personality changes, seizures, or stroke can occur. The Kidneys: Lupus nephritis (kidney damage) is a serious complication. The Blood: Low blood cell counts can occur. The Heart: Inflammation of the heart muscle or sac around the heart (pericarditis) can cause chest pain. The Lungs: Pain when breathing deeply can occur. The Digestive Tract: Abdominal pain, nausea, and vomiting may occur. Systemic lupus Erythematosus
- 53. Diagnosing Systemic LupusErythematosus (SLE) or lupus, involves a combination of clinical assessment, medical history, and laboratory tests. There's no single test that definitively diagnoses lupus, and it can be challenging to diagnose due to its variable symptoms and ability to mimic other conditions. Systemic lupus Erythematosus
- 54. Laboratory Tests: Antinuclear Antibody(ANA) Test: This is a common screening test for lupus, as almost all people with lupus have positive ANA. However, ANA can also be positive in other conditions, so it's not a definitive diagnosis for lupus alone. Other Autoantibody Tests: If ANA is positive, further tests may be ordered to identify specific autoantibodies, such as anti-dsDNA, anti-Sm, and anti- phospholipid antibodies. Complete Blood Count (CBC): This test can reveal low platelet, red blood cell, or white blood cell counts, which may be seen in lupus. Complement Protein Levels: Low complement protein levels can indicate lupus activity and help guide treatment decisions. Other Tests: Depending on the individual's symptoms, other tests like urinalysis, chest X-ray, and blood tests to assess kidney function may be performed. Systemic lupus Erythematosus
- 55. Rheumatoid arthritis (RA)is a chronic, autoimmune disease that primarily affects the joints, causing pain, swelling, and stiffness. It's characterized by inflammation in the lining of the joints, which can damage the tissue covering the bones. Rheumatoid arthritis (RA Symptoms of RA: Pain, swelling, and stiffness in more than one joint. Stiffness, especially in the morning or after periods of inactivity. Fatigue, weakness, and sometimes fever. Pain and stiffness in the same joints on both sides of the body. Possible extra-articular symptoms like eye, skin, or lung problems.
- 56. Blood Tests: Erythrocyte SedimentationRate (ESR) and C-reactive Protein (CRP): Rheumatoid Factor (RF) Antibodies: These antibodies are present in most people with rheumatoid arthritis. Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibodies: These antibodies are highly specific for rheumatoid arthritis, and their presence is a strong indicator of the disease. Diagnosis Magnetic resonance imaging (MRI) and ultrasound Rheumatoid arthritis (RA)
- 57. Symptoms Initial diagnosismay be missed in patients as diseases present with general symptoms Fever, muscle ache, fatigue, joint pain Disease specific manifests SLE – rash Sjogren’s – dry mouth, dry eyes
- 58. Diagnosis General tests C Reactive Protein Autoantibody titers (anti DNA, anti phospholipids, etc) Presence of Rheumatoid Factor Disease specific tests Neurological exam – MS Fasting glucose - Diabetes
- 59. Treatment The key totreating autoimmunity is immunomodulation
- 60. Years to Diagnosis 3.5 3.9 3.2 2.7 4.3 3.5 Crohn'sdisease Lupus (SLE) Multiple sclerosis Rheumatoid arthritis Sjogren's Disease Total - 1.0 2.0 3.0 4.0 5.0 60
- 61. Treatment Options • Anti-inflammatorydrugs • NSAIDS, Corticosteroids • Immunosuppressant drugs • Methotrexate • Radiation • Plamapheresis • Cell Blocking Reagents • aCD20 (Rituxan) • aCD3 (Teplizumab) • Cytokine Blocking Reagents • TNF (Humira, Enbrel)
- 62. ***********Remember*********** Autoimmunity is afailure of tolerance! Knowing the tolerance mechanisms the immune system uses, will help you better understand autoimmune diseases!