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Hypersensitivity Disorders Flashcards

1
Q

Type 1 HD - what is it? mediated by?

A

Immediate reaction provoked by re-exposure to an allergen.

IgE mediated - Mast cells release mediators resulting in vasodilation, increased permeability, smooth muscle spasm

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2
Q

Type 1 HD - Typical Symptoms?

A

Angioedema, urticaria, rhinoconjunctivitis, wheeze, diarrhoea and vomiting, Anaphylaxis

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3
Q

prevalence of allergic disorders in UK in children 13-14 years old

A

Asthma - 30% (4% also had concurrent clinical food allergy)
Allergic rhinitis - 20%
Atopic dermatitis - 15%
Food allergy - 2.3%

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4
Q

What is the atopic triad?

A

eczema, asthma and hay fever.

Possibly due to hygiene hypothesis

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5
Q 
T1HD - Atopic Dermatitis (infantile eczema) 
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Irritants, food and environmental
Pathology - Defects in beta defensin predispose to Staph aureus superinfection.
Diagnosis - clinical. 80% present in first year of life
Treatment - Emollients, skin oils, topical steroids, antibiotics, PUVA phototheraphy

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6
Q 
T1HD - Food Allergy
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Milk, eggs, peanuts, tree nuts, fish, shellfish
Pathology - IgE (anaphylaxis, OAS); cell mediated (coeliac); IgE/cell mediated (atopic dermatitis)
Diagnosis - Food Diary, skin prick test, RAST, Challenge test. Most resolved by adulthood
Treatment - Dietician, Food avoidance, Epipen, Control asthma if present

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7
Q 
T1HD - Oral Allergy Syndrome OAS
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Birch pollen + rosacae fruit, ragweed + melons, mugwort + celery (cross reactivity)
Pathology - exposure to allergen induces allergy to food. Symptoms limited to mouth 2% get anaphylaxis
Diagnosis - Clinically, skin prick testing can be useful
Treatment - Avoid food. If ingested was mouth, take anti-histamine

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8
Q 
T1HD - Latex food syndrome
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Chestnut, avocado, banana, patato, tomato, kiwi, papaya, eggplant, mango, wheat, melon
Pathology - Some foods have latex like components and hence latex allergy sufferers will also have food allergies
Diagnosis - Skin Prick Test
Treatment - Strict avoidance of causative food

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9
Q 
T1HD - Allergic Rhinitis
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - Seasonal (tree and grass pollen, fungal spores), Perennial (pets, house dust mites); Occupational (latex, lab animals)
Pathology - Nasal itch and obstruction, sneezing, anosmia, eye symptoms
Diagnosis - Pale bluish swollen nasal mucosa; Skin Prick Test and RAST
Treatment - Allergen avoidance, Anti-Histamine, Steroid Nasal spray, Sodium Cromoglycate Eye Drops, Oral Steroids, Ipratropium Nasal Spray, Grass pollen desensitisation

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10
Q 
T1HD - Acute Urticaria
Allergen?
Pathology?
Diagnosis?
Treatment?
A

Allergen - 50% idiopathic, 50% caused by food, drugs, latex, viral infections and febrile illnesses
Pathology - IgE medicated reaction. Wheals which completely resolve within six weeks
Diagnosis - Mainly clinical (sometimes skin prick test)
Treatment - Allergen avoidance, Anti-Histamines

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11
Q

Anaphylaxis

A

A severe systemic allergic reaction - respiratory diffculty and hypotension
IgE mediated mast cell degranulation - peanut, penicillin, stings, latex
Non- IgE mediated mast cell degranulation - NSAIDs, IV contrast, opiods, exercise

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12
Q

Management of Anaphylaxis

A

Elevate Legs, 100% Oxygen, IM adrenaline 500mcg, inhaled bronchodilators, Hydrocortisone 100mg IV, Chlorphenamine 10mg IV, IV fluids, Seek help

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13
Q

Investigations in allergy - Skin prick test

what is it used for? what is a positive test? anything that should be done before the test?

A

Useful to confirm clinical history. Negative test excludes IgE mediated allergy.
Positive control - histamine, negative control - dilutent
A positive test is a wheal > 2mm greater than the negative control
Discontinue antihistamines 48hrs before test (corticosteroids are ok)

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14
Q

Investigations in allergy - Quantitative specific IgE to putative allergen (RAST)
what it does? used for? sensitivity? indications?

A

Measure levels of IgE in serum against a particular allergen
Confirms dx of allergy and monitors response to anti-IgE treatment
Less sensitive/specific than skin prick testing
Indications - can’t stop anti-histamines, anaphylaxis, extensive eczema

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15
Q

Investigations in allergy - Component resolved diagnostics

A

Measures IgE response to a specific allergen protein (whilst conventional tests measure response to range of allergen proteins)

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16
Q

Investigations in allergy - Challenge test

A

Double blind oral food challenge in gold standard for food allergy BUT risk of severe reaction when testing.
Increasing volumes of offending food/drug are ingested under close supervision.

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17
Q

Investigations in allergy - During an acute episode

A

Measure mast cell tryptase (peak at 1-2hrs, baseline by 6hrs)

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18
Q

Type II Hypersensitivity Disorders

A

IgG or IgM antibody reacts with cell or matrix associated self antigen. Results in tissue damage, receptor blockade/ activation

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19
Q 
T2HD - Heamolytic Disease of the Newborn (HDN)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen- Antigens on neonatal erythrocytes
Pathology - Maternal IgG mediated retoculocytosis and anaemia
Diagnosis - Positive Direct Coombs Test
Treatment - Maternal Plasma exchange, exchange transfusion

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20
Q 
T2HD - Autoimmune Haemolytic Anaemia (+ ITP = Evan's Syndrome)
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Numerous autoantigens e.g. Rh blood group Ag
Pathogen - Destruction of RBC by auto antibody + complement + FcR + phagocytes, anaemia
Diagnosis - Positive Direct Coombs Test, Anti Red Cell Ab
Treatment - Steroids

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21
Q 
T2HD - Autoimmune Thrombocytopenic Purpura
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Glycoprotein IIb/IIIa on platelets
Pathology - Bruising/ Bleeding (purpura)
Diagnosis - Anti platelet Antibody
Treatment - Steroids, IVIG, Anti D antibody, Splenectomy

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22
Q 
T2HD - Goodpasture's Syndome 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Non- Collagenous domain of basement membrane collagen IV
Pathology - Glomerulonephritis, pulmonary haemorrhage
Diagnosis - Anti GBM Ab, Linear Smooth IF staining of IgG deposits on BM
Treatment - Corticosteroids and Immunosuppression

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23
Q 
T2HD - Pemphigus vulgaris 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - Epidermal Cadherin
Pathology - Non-tense blistering of skin and Bullae
Diagnosis - Direct immunofluoresence showing IgG
Treatment - Corticosteroids and Immunosuppression

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24
Q 
T2HD - Graves disease 
Antigen?
Pathology?
Diagnosis?
Treatment?
A

Antigen - TSH receptor
Pathology - Hyperthyroid
Diagnosis - Anti TSH-R Ab
Treatment - Carbimazole and Propylthiouracil

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25
``` T2HD - Myasthenia Gravis Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Acetylcholine receptor Pathology - Fatiguable muscle weakness, Double Vision Diagnosis - Anti- ACh-R Ab, abnormal EMG, Tensilion test Treatment - Neostigmine, Pyridostigmine, (if serious use IVIG and Plasmaphoresis)
26
``` T2HD - Acute Rheumatic Fever Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - M proteins on Group A strep Pathology - Myocarditis, Arthritis, Sydenham's Chorea Diagnosis - Clinical, based on Jones Criteria Treatment - Aspirin, Steroids and Penicillin
27
``` T2HD - Pernicious Anaemia Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Intrinsic Factor and Gastric Parietal Cells Pathology - decreased Hb, decreased B12 Diagnosis - Anti-gastric Parietal Cell Ab, Anti- IF Ab, Schilling Test Treatment - Dietary B12 or IM B12
28
``` T2HD - Churg-Strauss Syndrome (eGPA) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Medium and Small Vessel Vasculitis Pathology - Allergy -> Asthma -> Systemic Disease (Male predominance) Diagnosis - p-ANCA (against myeloperoxidase), Granulomas, Eosinophil, Granulomas Treatment - Prednisolone, Azathioprine, Cyclophosphamide
29
``` T2HD - Wegener's Granulomatosis (GPA) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Medium and Small Vessel Vasculitis Pathology - Sinus Problems, Lung Cavitations + haemorrhage, Cresentic Glomerulonephritis Diagnosis - cANCA (against Proteinase 3) granulomas Treatment - Corticosteroids, cyclophosphamide, co-trimoxazole
30
``` T2HD - Microscopic Polyangitis (MPA) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Pauci- immune necrotizing, small vessel vasculitis Pathology - Purpura, lived, many different organs affected Diagnosis - pANCA (against myeloperoxidase) Treatment - Prednisolone, Cyclophosphamide or Azathioprine, plasmaphoresis
31
``` T2HD - Chronic Urticaria Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Neducatuibs (NSAIDS), cold, food, pressure, Sun, Exercise, Insect stings, Bites and Idiopathic Pathology - Persistent Itchy Wheals Lasting >6Weeks. Associated with Angioedema in 50% of cases. IgG against FcR1 or IgG against IgE (exclude urticarial vasculitis in those who respond poorly to anti-histamine) Diagnosis - Challenge Test, ESR (Raised in Urticarial Vasculitis), Skin Prick Test Treatment - Avoid precipitants, Check for Thyroid disease, Preventative antihistamine, IM adrenaline for pharyngeal angioedema, 1% Menthol in Aqueous Cream for Pruritis (also Doxepin and Cyclosporin)
32
T3HD
IgG or IgM immune complex (Ab or soluble Ag) mediated tissue damage
33
``` T3HD - Mixed Essential Cryoglobulinaemia Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - IgM against IgG +/- hep C antigens Pathology - Joint pain, splenomegaly, skin, nerve and kidney involvement. Associated with Hep C Diagnosis - A mix of clinical and biopsies Treatment - NSAIDs, Corticosteroids and plasmaphoresis
34
``` T3HD - Serum Sickness Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Reaction to proteins in antiserum (Penicillin) Pathology - Rashes, Itching, arthralgia, lymphadenopathy, fever and malaise. Symptoms take 7-12 days to develop Diagnosis - Decreased C3. Blood shows immune complexes or signs of blood vessel inflammation Treatment - Discontinuation of precipitant, steroids, antihistamines (+/- analgesia)
35
``` T3HD - Polyarteritis Nodosa (PAN) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Hep B, Hep C virus antigens Pathology - Fever, fatigue, weakness, arthralgia, skin, nerve and kidney involvement, pericarditis and MI. Associated with Hep B Diagnosis - Diagnosed by clinical criteria and biopsy (high EST, high WCC, high CRP) "Rosary sign" Treatment - Prednisolone and Cyclophosphamide
36
``` T3HD - Systemic Lupus Erythematosis (SLE) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Mainly intracellular components; DNA, histones, RNP Pathology - M:F = 1:9, 4/11 of these - serositis, seizures, pathos ulcers, arthritis, photosensitivity, discoid rash, malar rash, haematology, kidney findings, Antinuclear antibody (ANA +ve), immunological findings (anti-dsDNA, anti-sm) Diagnosis - low C4 (low C3 only in SEVERE disease) Ab's to dsDNA, Histones (drug induced), Ro, La, Sm, U!RNP high ESR, normal CRP Treatment - Mainly; Analgesia, steroids and cyclophosphamide
37
T4HD
Delayed hypersensitivity, T-cell mediated
38
``` T4HD - Type 1 Diabetes Mellitus Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Pancreatic Beta Cell Proteins (glutamate Decarboxylase GAD) Pathology - Insulitis, Beta cell destruction Diagnosis - Blood Glucose, Ketonuria, Glutamate Decarboxylase Antibodies, Islet cell antibodies Treatment - Insulin via injection or continuous infusion
39
``` T4HD - Multiple Sclerosis Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Oligodendrocytes proteins (Myelin basic protein, Proteolipid protein) Pathology - Demyelinating disease, preicascular inflammation, paralysis, Ocular lesions Diagnosis - CSF shows Oligoclonal Bands or IgG on electrophoresis Treatment - Corticosteroids, Interferon-beta
40
``` T4HD - Rheumatoid Arthritis (also type 3: IgM Ab vs Fc region of IgG) Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Antigen in Synovial Membrane Pathology - Chronic Arthritis, Rheumatoid Nodules, Lung Fibrosis Diagnosis - X-Ray, Rheumatoid Factor (85% Sensitive), Anti-CCP (95% specific), high ESR and CRP Treatment - Analgesia, Steroids, DMARDs
41
``` T4HD - Contact Dermatitis Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Environmental Chemicals, Poison Ivy, Nickel Pathology - Dermatitis with usually short-lived itching, blisters and wheals Diagnosis - Clinical or use Patch Test Treatment - If no resolution use corticosteroids or antihistamines
42
``` T4HD - Mantoux Test Antigen? Pathology? Diagnosis? Treatment? ```
Antigen - Tuberculin | Pathology - Skin Induration indicates TB exposure
43
``` T4HD - Crohn's Disease Antigen? Pathology? Diagnosis? Treatment? ```
Pathology - TH1 mediated. Chronic inflammation in skip lesions in GIT. NOD2 gene mutation in 30% Diagnosis - Biopsy of lesion (can affect any part of GIT from mouth or anus) Treatment - Antibiotics, anti-inflammatory drugs e.g. Mesalazine, TNF alpha antagonists e.g. infliximab, steroids
44
HLA Associations - Ankylosing spondylitis - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA B27 | - Relative Risk (fold) - 87
45
HLA Associations - Goodpasture's Syndrome - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA DR15/DR2 | - Relative Risk (fold) - 10
46
HLA Associations - Graves Disease - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA - DR3 | - Relative Risk (fold) - 4
47
HLA Associations - SLE - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA - DR3 | - Relative Risk (fold) - 6
48
HLA Associations - T1DM - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA DR3/DR4 | - Relative Risk (fold) - 25
49
HLA Associations - Rheumatoid Arthritis - Susceptibility Alelle - Relative Risk (fold)
- Susceptibility Alelle - HLA-DR4 | - Relative Risk (fold) - 4
50
PTPN22
Tyrosine phosphatase expressed in lymphocytes, associated development of RA, SLE, and T1DM
51
CTLA4
receptor for CD80/CD86 expressed by T cells, transmits inhibitory signal to control T cell activation, Associated with SLE, T1DM, Autoimmune thyroid disease
52
CREST syndrome - Limited Cutaneous Scleroderma | - what does CREST stand for
``` Calcinosis Raynaud's (O)Esophageal dysmotility Sclerodactyly Telangiectasia (+ primary pulmonary hypertension) ```
53
Diffuse Cutaneous Scleroderma | - what does it involve?
CREST + GIT+ interstitial pulmonary disease + renal problems
54
Sjogren's Syndrome | - who is affected?
M:F 1:9, onset in late 40s
55
IPEX syndrome | - what does it stand for?
Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritance syndrome + autoimmune diseases
56
Sjogren's Syndrome | - symptoms?
Dry mouth (xerostomia), eyes (keratoconjunctivitis sicca), nose and skin May affect kidneys, blood vessels, lungs, liver, pancreas and PNS, may get parotid or salivary gland enlargement Anti-Ro and anti-La antibodies present Use Schirmer test to measure production of tears- assessing for dry eyes
57
Sjogren's Syndrome | - Ab present?
Anti-Ro and anti-La antibodies present | Use Schirmer test to measure production of tears- assessing for dry eyes
58
Sjogren's Syndrome | - what test is used?
Use Schirmer test to measure production of tears- assessing for dry eyes
59
IPEX syndrome | -Symptoms?
Eczematous dermatitis, nail dystrophy and autoimmune skin conditions such as alopecia universals and bullous pemphigoid
60
IPEX syndrome | -age of death?
Most affected children die within the first 2 years of life
61
IPEX syndrome | -inheritance?
X-linked recessive disorder with exclusive expression in males
62
IPEX syndrome | -treatment?
Bone marrow transplant is the only cure. can use immunomodulators to help
63
CREST syndrome - Limited Cutaneous Scleroderma - Antibodies for diagnosis - increases risk for what?
Anti-centromere Antibodies for diagnosis
64
CREST syndrome - Limited Cutaneous Scleroderma | -increases risk for what?
High risk of Lung Fibrosis and Renal Crisis
65
Diffuse Cutaneous Scleroderma | - Antibodies?
Anti- Topoisomerase/ Scl70, RNA Pol 1,2 and 3, Fibrillarin Antibodies
66
Diffuse Cutaneous Scleroderma | - who is affected?
Females: males 4:1
67
Coeliac Disease | -what is it?
Failure of tolerance to gluten. Villous atrophy and enteropathy
68
Coeliac Disease | -Symptoms?
GIT discomfort, constipation, diarrhoea, bloating, fatigue
69
Coeliac Disease | -what does it go on to cause deficiencies in?
Iron, B12, Folate, Fat, Vitamins A, D, E & K and calcium deficiencies
70
Coeliac Disease | -Immunogloblins involved?
``` IgA EMA (anti- endomysial antibody) disappears with exclusion diet (95% specific, 85% sensitive) IgA TGT (anti- transglutaminase antibody) - 95% specific, 90-94% sensitive IgG anti-gliadin antibody - most persistent (30-50% specific, 57-80% sensitive) ```
71
Coeliac Disease | -Test
Gold Standard test is to do a duodenal biopsy but it is not first line
72
What autoantibody is associated with ... Antiphospholipid Syndrome (Hugh's syndrome) ?
IgG Antibodies against cardiolipin and beta2 glycoprotein, lupus anticoagulant
73
What autoantibody is associated with ...Autoimmune Hepatitis?
IgG - Anti-smooth muscle antibody, anti-liver kidney microsomal-1 (anti-LKM-1). Anti Soluble Liver antigen (anti-SLA)
74
What autoantibody is associated with ...Autoimmune haemolytic anaemia?
IgG- Anti-Rh blood group antigen
75
What autoantibody is associated with ... Autoimmune Thrombocytopenic Purpura?
IgG - Anti-Glycoprotein IIb-IIIa or Ib-IX antibody
76
What autoantibody is associated with ... Churg-Strauss Syndrome (eGPA)?
Perinuclear/protoplasmic-stainng antineutrophil cytoplasmic antibodies (p-ANCA)
77
What autoantibody is associated with ... Coeliac disease?
IgA - Anti-tissue transglutaminase antibody, Anti-endomysial antibody
78
What autoantibody is associated with ... Congenital heart block in infants of mothers with SLE?
IgG - Anti-Ro antibody
79
What autoantibody is associated with ... Dermatitis hepetiformis?
IgA - anti-endomysial antibody
80
What autoantibody is associated with ...Dermatomyositis?
IgG - Anti-Jo-1 (t-RNA Synthetase)
81
What autoantibody is associated with ... Diffuse Cutaneous Scleroderma?
IgG - Antibodies to Topoisomerase/Scl70, RNA Pol I, II, III, Fibrillarin (nucleolar pattern)
82
What autoantibody is associated with ... Goodpasture's Syndrome?
IgG - Anti-GBM antibody
83
What autoantibody is associated with ...Graves Disease?
IgG - Anti-TSH Receptor antibody (stimuatory antibody)
84
What autoantibody is associated with ... Hashimoto's Thyroiditis?
IgG - Antibodies to Thyroiglobulin and thyroperoxidase
85
What autoantibody is associated with ... Limited Cutaneous scleroderma (CREST)
IgG - Anti-centromere antibody
86
What autoantibody is associated with ... Microscopic Polyangitis (MPA)?
IgG- Perinuclear.protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA)
87
What autoantibody is associated with ... Mixed connective tissue disease?
IgG- Anti-U1RNP antibody (speckled pattern)
88
What autoantibody is associated with ... Myasthenia Gravis?
IgG- Anti-ACh Receptor Antibody
89
What autoantibody is associated with ... Pernicious anaemia?
IgG - Antibodies to gastric parietal cells (90%) and intrinsic factor (50%)
90
What autoantibody is associated with ... Polymyositis?
IgG - Anti-Jo-1 (t-RNA Synthetase)
91
What autoantibody is associated with ... Primary Biliary Cirrhosis?
IgG- Anti-mitochondrial antibody
92
What autoantibody is associated with ... Rheumatoid Arthritis?
IgG- Anti-CCP antibodies, Rheumatoid factor
93
What autoantibody is associated with ... Sjogren's Sundrome?
IgG - Anti-Ro, Anti-La antibody (speckled pattern), 60-70% have positive RF
94
What autoantibody is associated with ... Systemic Lupus Erthematosis?
IgG - Antibodies to dsDNA+ histones (Homogenous) and Ro LA, Sm, U1RNP (speckled)
95
What autoantibody is associated with ... Type 1 Diabetes Mellitus?
IgG - Antibodies to Glutamate Decarboxylase and pancreatic beta cells
96
What autoantibody is associated with ... Wegener's Granulomatosis (GPA)?
IgG - Cytoplasmic antinutrophil cytoplasmic antibodies (c-ANCA)

Path Immunology (8 decks)

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