clinical immunology
DESCRIPTION
Clinical Immunology. Conleth Feighery John Jackson. Auto-antibodies. Often very helpful in making diagnosis Rarely entirely specific – i.e. can occur in range of diseases ANA, rheumatoid factor examples of this. Auto-antibodies. ANA usually positive in connective tissue diseases - CTD - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/1.jpg)
Clinical Immunology
Conleth FeigheryJohn Jackson
![Page 2: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/2.jpg)
Auto-antibodies
• Often very helpful in making diagnosis• Rarely entirely specific – i.e. can occur in
range of diseases• ANA, rheumatoid factor examples of this
![Page 3: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/3.jpg)
Auto-antibodies
• ANA usually positive in connective tissue diseases - CTD
• Sub-categories of ANA may define the type of CTD
• Double stranded DNA – exclusive to SLE• Antibodies to “extractable nuclear antigens”
define other types of CTD
![Page 4: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/4.jpg)
Case 6
• 32 year old bank official• Dry mouth +++• Water to bedside• Customer interaction difficult• Fatigue +
![Page 5: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/5.jpg)
Case 6
Examination -• Reduced saliva• Sub-mandibular gland
swollen• Dental damage
![Page 6: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/6.jpg)
Extractable nuclear antigens
• Antibodies to sub-fractions of nucleus
• Ro antibodies – found in a ‘common’ CTD called Sjogren’s syndrome – in ~ 75% of pts
• Also found in other CTDs including lupus – so not specific
![Page 7: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/7.jpg)
Sjogren’s syndrome
Features • Inflammation of glands - lacrimal, salivary• Symptoms - dry eyes, dry mouth• Joint, muscle symptoms - sometimes• Associated CTD - RA, SLE ….• Older females
![Page 8: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/8.jpg)
Case 6 - Sjogren’s syndrome
Confirming the diagnosis - • History• Quantify tears, saliva production• Biopsy ?• Autoantibodies– ANA positive– Ro antibody positive
![Page 9: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/9.jpg)
Case 6 - Sjogren’s syndrome
Cause -• Lymphocytic infiltrate of exocrine glands• Salivary, lacrimal, genital glands affected• Monoclonal expansion of B cells can occur• Lymphoma may develop
![Page 10: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/10.jpg)
Case 6 - Sjogren’s syndrome
• Associates with other diseases• SLE• Rheumatoid arthritis• Thyroid disease• Primary biliary cirrhosis
• HLA genes associated
![Page 11: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/11.jpg)
Ro antibodies
Can cross placenta and rarely -• Cause complete congenital heart block– Damage to heart conducting system
• Cause skin inflammation – ‘neonatal lupus’
![Page 12: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/12.jpg)
ENA antibodies - valuable
Help define type of CTD -• Sjogren’s syndrome - Ro, La antibodies• SLE - Sm antibodies• Scleroderma - Scl 70 antibodies• Anti-RNP - mixed connective tissue disease
![Page 13: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/13.jpg)
Case 7
• 44 year old female• Arthralgia, myalgia• Raynaud’s phenomenon• Fatigue
![Page 14: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/14.jpg)
Case 7
Examination -• Mild sclerodactyly• Telangiectasia, hands, face
![Page 15: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/15.jpg)
Sclerodactyly of fingers
Sclero = hardDactyly = digit
![Page 16: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/16.jpg)
Telangiectasia
![Page 17: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/17.jpg)
Case 7 diagnosis is CREST
• Clinical findings• Centromere auto-antibody
• C = calcinosis• R = Raynaud’s• E = oesophagus• S = sclerodactyly• T= telangiectasia
![Page 18: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/18.jpg)
Anti-centromere antibody -ANA observed in dividing cells
Positive in 70% of CREST patients
![Page 19: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/19.jpg)
Systemic sclerosis (scleroderma)
• More severe version of CREST• Skin thickening – arms, thorax, face• GIT structures affected
– oesophagus – dysphagia- small intestine – dysmotility, malabsorption
• Lungs – fibrosis• Caused by deposition of collagen -
unexplained
![Page 20: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/20.jpg)
Systemic sclerosis (scleroderma)
• Auto-antibody – to a ENA• Anti-Scl 70 - antigen is enzyme topoisomerase I
![Page 21: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/21.jpg)
Case 8
• Female, 54 years• Fatigue• Skin itch x 2 years• Mild icterusExamination• Generally healthy• Icterus confirmed• Liver, spleen size normal
![Page 22: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/22.jpg)
Liver auto-immunity
• Primary biliary cirrhosis• Females• Middle-aged• Inflammatory process focused on intra-
hepatic biliary tree• Liver failure – common reason for liver
transplantion
![Page 23: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/23.jpg)
Case 8 auto-antibody tests
2 helpful auto-antibodies – • Anti-mitochondrial antibody
Confirmatory antibody to enzyme -• Anti-pyruvate dehydrogenase (PDH)
![Page 24: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/24.jpg)
Mitochrondrial antibody
Kidney tubule tissue
![Page 25: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/25.jpg)
Primary biliary cirrhosis
Liver granuloma – early disease Established cirrhosis
![Page 26: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/26.jpg)
Chronic active hepatitis
• Females• Often in younger age group – 20s• Less common form of liver disease• Antibodies to “smooth muscle” BUT not
specific for this disease
![Page 27: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/27.jpg)
Connective tissue disease
Vasculitis
![Page 28: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/28.jpg)
Vasculitis
• Inflammation - focus on blood vessels• Damage to blood vessel -– local thrombosis, – haemorrhage – damage to tissue it supplies
![Page 29: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/29.jpg)
Vasculitic lesions in vasculitis
![Page 30: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/30.jpg)
WG – case
No other systemic symptomsDecision to treat with cyclophosphamide, steroids
![Page 31: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/31.jpg)
Blood vessel size in vasculitis
![Page 32: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/32.jpg)
Vasculitis
• Clinical presentation can be obscure• Systemic inflammatory disease - ? cause• Pyrexia of unknown origin• Infection ??• Malignancy ??
![Page 33: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/33.jpg)
Wegener’s granulomatosis
• Small vessel vasculitis• Classically affects -
Upper respiratory tract – nose, ears, sinusesLower respiratory tract - lungsKidneys
• But can affect any organ, including skin• GIT sometimes, but less common
![Page 34: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/34.jpg)
Wegener’s granulomatosis
• Bleeding is often the clue!• Nasal – epistaxis• Lungs – haemoptysis• Kidney – haematuria
• PUO – pyrexia of unknown origin • Systemic symptoms – joint, muscle pain
![Page 35: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/35.jpg)
Wegener’s - clinical features
Episcleritis Saddle nose deformity
![Page 36: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/36.jpg)
Wegener’s granulomatosis
• Diagnosis often missed in past• Not uncommon disorder – but many medics
have not seen a case• 100+ cases diagnosed in 15 years, SJH• Clinical features can be atypical• Auto-antibody – specific, sensitive – use
leading to increased diagnosis
![Page 37: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/37.jpg)
WG – case , 1992
• RE - 26 year old Australian, on world tour• 3 week history of haemoptysis• Possible weight loss of 6kg• Arthralgia - large joints• Rash - macular, erythematous
![Page 38: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/38.jpg)
WG – case
• Rapid deterioration - in 1 week• Temp 38• Synovitis of small joints• Episcleritis • Blistering necrotic skin rash• Haemoptysis +++
![Page 39: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/39.jpg)
WG - case 1
Differential diagnosis -• Tuberculosis ?• Carcinoma of lung ?• Bacterial infection ?• Auto-immune disease – vasculitis ?
![Page 40: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/40.jpg)
WG - case 1
• WCC - 25 x 109/L• Urine - haematuria, proteinuria• Lung biopsy - alveolitis (ICU)• Auto-antibody screen + C-ANCA• DIAGNOSIS - Wegener’s
![Page 41: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/41.jpg)
C-ANCA PR3+
![Page 42: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/42.jpg)
Wegener’s auto-antibodies
First step -• Anti-neutrophil cytoplasmic antibody = ANCA• Immunofluorescence testSecond step -• Anti-PR3• ELISA
![Page 43: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/43.jpg)
Wegener’s granulomatosis
• Why is the diagnosis missed ?• Limited Wegener’s – upper airways alone– Sinusitis– Rhinitis – Deafness
• Skin or other organ alone• Diagnosis not considered
![Page 44: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/44.jpg)
Wegener’s granulomatosis
• Treatment• Immunosuppressive drugs –
cyclophosphamide• Steroids• Good response usually – mortality of disease
reduced +++
![Page 45: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/45.jpg)
Wegener’s granulomatosis
However -• Relapse is very common ~ 50%• Further organs may become involved• Chronic renal damage may develop – dialysis,
transplant
![Page 46: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/46.jpg)
Another case ……
• Another example of connective tissue disease• Auto-antibodies help “dissect” the condition
![Page 47: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/47.jpg)
Case 8.
• 24 year old female parachutist• Presented with marked ecchymosis - sites of
parachute strap marks• Mild arthralgia, fatigue• DVT in calf 1 year previously
![Page 48: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/48.jpg)
Case 8.
• Tests - v.low platelet count 7 x 109
• WCC count 3 x 109
• Haemoglobin 10g• ANA positive, titre 640• Diagnosis ??
![Page 49: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/49.jpg)
Case 8.
• Further auto-antibody tests– Anti-cardiolipin antibody ++– Anti-beta2-glycoprotein antibody ++
• Diagnosis ??• Anti-phospholipid syndrome
![Page 50: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/50.jpg)
Anti-phospholipid syndrome
• Classic features• Thrombosis - recurrent• Thrombocytopaenia• Miscarriages - recurrent
![Page 51: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/51.jpg)
Anti-phospholipid syndrome
• Associated with connective tissue disease - especially SLE
• Overlaps with• ITP - idiopathic thrombocytopenic purpura
• May have clinical features like - TTP - thrombotic thrombocytopenic purpura ??
![Page 52: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/52.jpg)
Case 8 - 2006
• Remained well for 10 years• Developed mild arthritis• dsDNA antibody positive
![Page 53: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/53.jpg)
Case 8 - January 2006
• Dyspnoea on exertion• Anaemia, low WCC, low platelets• Hypertension• Marked lower limb oedema
![Page 54: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/54.jpg)
Case 8 - 2006
• Casts - red cells in urine• Marked proteinuria - nephrotic• Renal biopsy - diffuse proliferative
glomerulonephritis (class IV)• Diagnosis - SLE
![Page 55: Clinical Immunology](https://reader035.vdocuments.site/reader035/viewer/2022062806/56814ef7550346895dbc86f6/html5/thumbnails/55.jpg)
The end
Next termImmunodeficiency disorders
Allergy