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Year 2 clinical pathology > week 3 Autoimmune disease and diagnosis > Flashcards

week 3 Autoimmune disease and diagnosis Flashcards

1
Q

what is the definition of sensitivity?

A

measure of how good is the test in identifying people with the disease

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2
Q

what is the definition of specificity?

A

measure of how good is the test at correctly defining people without the disease

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3
Q

what is the definition of Positive predictive value ?

A

The proportion of people with a positive test who have the target disorder

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4
Q

what is the definition of negative predictive value ?

A

The proportion of people with a negative test who do not have the target disorder.

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5
Q

Give a example of a non specific diagnostic test?

A

Inflammatory markers

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6
Q

Give a examples of a disease specific diagnostic test?

A

Autoantibody testing

HLA typing

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7
Q

what is erythrocyte sedimentation rate (ESR)?

A

old way of measure the inflammation in the serum

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8
Q

how does ESR work?

A

Put blood in a narrow capillary tube

Viscosity of the plasma increase if you have an ongoing autoimmune response of inflammation –> thicker it is the higher grade of inflammatory response

Takes a while for ESR to dissolve fully

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9
Q

What is C reactive protein when is it produced?

A

liver produces after acute phases of systemic inflammation of the liver

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10
Q

how is CRP used ?

A

Rapidly produced and rapidly used up –> use the marker in space of 12 to 24 hrs –> use it to see how the treatment is working

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11
Q

give example of Non-specific markers of systemic inflammation?

A 
Erythrocyte sedimentation rate (ESR
CRP
Ferritin
Fibrinogen
Haptoglobin
Albumin
Complement
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12
Q

what does low albumin in the blood mean?

A

liver disease/damage

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13
Q

What happens to levels of ferritin and fibrinogen in inflammation?

A

Increase in acute inflammatory response

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14
Q

What are Antinuclear Ab? (ANA)

A

Auto-Ab which recognise structures or substances found in the nucleus of cells - involved in alot of autoimmune diseases

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15
Q

What is meant by Extractable nuclear antigens (ENAs)?

A

Structures found in the nucleus which are the specific targets of different types of Anti-nuclear Ab

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16
Q

how do you detect ANA?

A

Use large fibrocyte type cells - they have a large nucleus Spread them along the microscope slide and incubate with patients serum If ANA is present in the serum it will bind to the cells You can visualise these bound ANAs using a second Ab with a fluorescent marker which binds to the constant Fc region Thus by visualising the fluoresence you can detect the presence of ANAs in the serum

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17
Q

Anti-DNA ANAs are likely to give what kind of fluorescent pattern?

A

Peripheral or homogenous

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18
Q

Anti-histone and anti-DNP ANAs are likely to give what kind of fluorescent pattern?

A

Homogenous

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19
Q

what are the techniques to detect ENA’s?

A

Immunoblots
Individual ELISA’s
Combination of antigens

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20
Q

what are antibodies to ENA’s are assoicated to what?

A

To particular connective tissue disorders

Including Systemic lupus erythematosus SLE

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21
Q

How does a microbead-based immunoassay to identify non-organ specific autoantibodies work?

A

1) Have beads with a unique internal colour which can be recognised by a machine and gives them a unique identity 2) To each bead you can attach a certain Ag you want to measure 3) Incubate these beads with patient serum 4) If auto-Ab are present they will attach to the bead with their specific target Ag 5) Use a second fluorescently labelled Ab which binds to any bound auto-Ab 6) Put beads through a machine, tells you which bead it is (ie. which specific Ag) and whether anything is attached

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22
Q

what antibody is assoicated with dsDNA (antigen)? What des this cause?

A

Anti-ds DNA

High specificity for SLE –> often correlates with high active severe disease

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23
Q

what is RF?

A

It is a antibody directed against the Fc portion of IgG

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24
Q

When is RF found?

A

Commonly found in rheumatoid arthritis

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25
Why is Rf not used for diagnostic of the disease?
Not used because it has sensitivity and specificity around 70% Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections such as Hep B)
26
How does the RF cause a immune response?
RF and IgG join to form immune complexes which contribute to the immune process
27
What can high concentation of RF cause?
Vasculitis
28
What is VAsculitis?
is a group of disorders that destroy blood vessels by inflammation
29
What biomark is used to detect Rheumatoid arthritis? How specific is it?
Anti-CCP (ACPA) more specific (95%) for RA then RF
30
what does a positive ACPA indicate?
ACPA positive patients tend to have more severe and erosive disease
31
what is the advantage of ACPA ?
Much more specific and can pick up the disease before the symptoms are present so much more effective treatment?
32
Anti-neutrophilic cytoplasmic Ab (ANCA) were first described as an auto Ab specific for what?
Wegeners granulomatosis
33
what is Wegeners granulomatosis?
t is a form of vasculitis (inflammation of blood vessels) that affects small- and medium-size vessels in many organs.
34
what does Cytoplasmic (c)ANCA show?
Granular fluorescence of neutrophil cytoplasm with nuclear sparing
35
what does Perinuclear (p)ANCA show?
Apparent fluorescence of the nucleus only | but sparing the cytoplasm
36
what are the target antigens of Cytoplasmic (c)ANCA show?
PR3 (90%) Azurocidin Lysozyme (1%) MPO
37
what are the target antigens of Perinuclear (p)ANCA?
``` MPO (70%) Azurocidin B-glucuronidase Cathepsin G (5%)* PR3 ```
38
Name 3 ANCA associated systemic vasculitidies (AAV)?
1) Granulomatosis with polyangitis (Wegener's granulomatosis) 2) Microscopic polyangitis 3) Churg-Strauss syndrome
39
In Wegener's granulomatosis which Ag is more common, PR3 or MPO?
PR3 much more common than MPO
40
In microscopic polyangitis which Ag is more common PR3 or MPO?
MPO is more common than PR3
41
In Churg-Strauss syndrome which Ag is more common, MPO or PR3?
MPO is more common than PR3
42
what is PR3?protein used by neutrophil to destroy antibacterial
protein used by neutrophil to destroy antibacterial
43
why is Positive ANCA extremely useful ?
useful in suggesting the diagnosis in the proper clinical setting
44
what does negative ANCA does not exclude?
AASV since 10%-50% of patients may be ANCA neg
45
what does Reemergence of ANCA pos in a patient who was ANCA neg whilst in remission suggest?
risk of disease flare
46
what is Anti-mitochondrial Ab specific for?
primary biliary sclerosis
47
what is ANCA assoicated to waht condition?
ANCA-associated vasculitis
48
ANCA positivity is highest in which ANCA associated vasculitis?
Wegener's granulomatosis followed by microscopic polyangitis followed by Churg-Strauss syndrome
49
what is the gold standard for testing AASV?
Histopathology
50
what is histopathology?
refers to the microscopic examination of tissue in order to study the manifestations of disease
51
what antibodies are found in found in autoimmune hepatitis?
Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs,
52
what antibodies are found in autoantibodies in type 1 diabetes?
islet cell antibodies anti-GAD65 anti-GAD67 anti-insulinoma antigen 2 (IA-2) insulin autoantibodies (IAAs)
53
what happen to the antibodies are the type 1 diabetes progress?
Disappear with progression of disease and total destruction of β islet cells
54
what is the Role of autoantibodies in diagnosis of type I DM?
Disease conformation to identify relatives and patients at risk of developing autoimmune diabetes Negative predictive value of ICA and IAA is almost 99% Increased risk of disease development with greater number of different autoantibodies present and younger age of patient
55
what are the main characterstics of autoinflammation?
seemingly spontaneous attacks of systemic inflammation no demonstrable source of infection as precipitating cause absence of high-concetration of autoantibodies and antigen specific autoreactive T cells No evidence of auto-antigenic exposure
56
what are the 3 factors that are involved in autoimmunity?
genes, immune regulation and environment
57
what are the two types of HLA and where are they found?
HLA 1 found on all cells | HLA 2 --> found on antigen presenting cells
58
what does mutation in FoxP3 cause?
mutation of FoxP3 causes failure to develop regulatory T cells – severe autoimmunity from birth For example X linked syndrome
59
what does mutation in PTPN22 cause?
mutations in PTPN22 cause T cells to be activated more easily – stronger immune response in general Example Type 1 diabetes and RA
60
where do B cells and T cells grow?
Bone marrow and Thymus
61
how does central tolerance in bone marrow and thymus work.
The B cell or T cell have specific receptors that bind to the peptide antigen MHC --> the B cell or T cell reacts to the self antigens then it will get destroyed --> negative selection and the ones that are released are through positive selection. It is also at this point where all the different types of receptors are produced.
62
what is Peripheral tolerance?
Peripheral tolerance is immunological tolerance developed after autoreactive T and B cells mature and enter the periphery.
63
what are the other causative associations of autoimmune disease ?
Sex (hormonal influence): women >> men Age--> autoimmunity more common in elderly + due accumulation of environmental factors Sequestered Antigents May be recognised as foreign by the immune system Environmental triggers Infection Trauma-tissue damage smoking
64
how does autoreactive B cells and autoantibodies cause clinical disease?
directly cytotoxic activation of complement Interfere with normal physiological function General inflammation and end organ damage
65
how does autoreactive T cells cause clinical disease?
Directly cytotoxic Inflammatory cytokine production General inflammation and end organ damage
66
when is the usual onset of autoimmune disease and does it affect males or females more?
Onset in middle age, old age | More common common in the elderly and women
67
what are the characteristics of autoimmune disease?
``` Can affect any organ of body Leads to loss of organ function Lifelong-chronic condition Characteristic exacerbation and remission Common for diseases to overlap ```
68
what are autoimmune disease classified into?
More than 100 different diseases Traditionally divided into organ specific or systemic
69
what are characteristics of autoimmune Organ specific disease?
Affect a single organ Autoimmunity restricted to autoantigens of that organ Overlap with other organ specific diseases Autoimmune thyroid disease is typical
70
what are characteristics of autoimmune systemic disease?
Affect several organs simultaneously Autoimmunity associated with autoantigens found in most cells of body Overlap with other non-organ specific diseases Connective tissue diseases are typical
71
what symptoms can be seen with over reactive thyroid?
anxiety, weight loss, diarrhea and palpitations. Although it is winter she hardly notices cold weather. She finds it almost impossible to sleep Abudance of energy Examination: rapid pulse sweaty hands. has rapid reflexes
72
what symtpoms can be seen with under reactive thyroid?
recent tiredness and difficulty concentrating had experienced a decline in memory decreased frequency of bowel movements increased tendency to gain weight chille with slight sweat even when warm examination --> pulse rate low and high BP Delayed relaxation
73
what is Hashimotos thyroiditis?
Destruction of thyroid follicles by autoimmune process Associated with autoantibodies to thyroglobulin and to thyroid peroxidase Leads to hypothyrodism
74
what is hypothyrodism?
Abnormal low activity of thyroid gland in retardation of growth and mental development in children and adults.
75
what is Graves Disease?
Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody Leads to hyperthyroidism The antibody is not attacking the thyroid but over stimulating the thyroid organ
76
what is the result of hyperthyrodism?
Causes rapid heartbeat and an increased rate of metabolism.
77
what are symptoms of Myasthenia gravis?
Difficulty keeping his eyes open, speaking and swallowin Does not smile any more His symptoms get worse as the day goes on
78
Pathologically what happens in Mysathenia gravis?
anti ACH receptors bind to the ACH receptors preventing the ACH from binding to them --> so you get no stimulation of muscles
79
what is the cause of Pernicious anaemia?
lack of B12
80
What are possible symptoms of Pernicious anaemia?
Fatigue, tingling in the feet and vitiligo
81
what is vitiligo?
a condition in which the pigment is lost from areas of the skin, causing whitish patches, often with no clear cause.
82
why is there a failure for the uptake of B12 in Pernicious anaemia? What is the treatment?
The B12 does not attach to RF in the stomach so it can be absorbed Treat it by injecting B12 every 3 months
83
Give me 4 examples of connective tissue disease?
Systemic lupus erythematosus Scleroderma Polymyositis Sjogrens syndrome
84
what are the symptoms of systemic lupus erythematosus ?
Photosensitive malar rash Mouth ulcer Arthralgia Alopecia fever general tiredness arthritis
85
In SLE what type of antibodies do you get?
Anti nucleus antibodies. | In SLE the immune system forms antibodies against proteins and DNA in the nuclei of cells
86
How do the antibodies get access to the nucleus of a cell?
There is failure of apoptosis which exposes the nuclei --> this is apparent particularly when sun damages cells but apoptosis does not properly happen
87
what does anti nuclear antibodies form in SLE?
Anti nuclear antibodies and their antigen form immune complexes
88
What do immune complexes do?
Immune complexes deposit in any organ – activate complement and cause inflammation
89
What happens in Lupus Nephritis?
Happens in 20% of people with lupus. Immune complex deposition Inflammation Leakly glomerulus Loss of renal function due to deposition of a lot of protein in the glomerular Scarring Irreversible renal failure
90
what is the name of glomerular inflammation?
glomerulonephritis
91
What are the internal organs invovled in SLE? What disease is associated with that organ?
Kidney --> Lupus nephritis Lung ---> Pleurisy/ Pleural Effusion Brain --> Cerebrak lupus, seizures, strokes
92
how you test and treat SLE?
Test for Antinuclear Antibodies Treat by using immunosuppression, B cell depletion and Glucocrticoids
93
What is pupura? What can it be a indicator of?
blocked blood vessels in the skin --> all that skin dies due to lack of blood supply. Can be a indicator of meningitis or vasculitis
94
What causes Vasculitis?
Anti neutrophil Cytoplasmic Antibodies (ANCA)
95
What is Vasculitis and how is it formed?
Inflammation of the vessel wall caused by white blood cells that have been stimulated by ANCA
96
What are the 3 forms of ANCA vasculitis?
Microscopic Polyangiitis (MPA) Granulomatosis with Polyangiitis (GPA) Eosinophilic Granulomatosus with Polyangiitis (EGPA)
97
In Eosinophilic Granulomatosus with Polyangiitis (EGPA) what is the pathological affect?
Get granuloma --> mass of inflammed tissue | Polyangiitis --? inflammation of many vessels
98
Where does Granuloma and Polyangiitis occur in EGPA?
Granuloma --> destruction lesion in nose, sinuses, trachea, lung, orbits Polyangiitis --> inflammation of small vessels causing inflammation adn damage to the skin, kidney, lung and gut
99
What is granulomata and do all forms of ANCA vasculitis have this?
Only some forms Its destructive masses of chronic inflammatory tissue Tend to affect upper airways and lungs May cavitate
100
Does polyangiitis happen in all forms of ANCA vasculitis?
yes
101
How do you test and treat ANCA vasculitis?
test for ANCA Treat by using immunosuppression, B cell depletion and Glucocrticoids
102
What are the characterstics of Raynaud's Phenomenon?
Common in young women Runs in families ANA negative Fairly Harmless
103
What are the characterstics of secondary Raynaud's Phenomenon?
ANA positive | May be assoicated with Scleroderm and also SLE
104
What are the symptoms of Scleroderma?
Digital ulcers due to tighetening and ischaemia Skin fibrosis and tighetening around the mouth Lung fibrosis
105
What are the treatment of Scleroderma?
Vascodilating drugs, Cylcoposphamide, autologous stem cell transplant
106
List 4 organ specific autoimmune diseases
Hashimotos thyrioditis --> thyriod Graves disease --> thyroid Myaesthenia Gravis Pernicious Anaemia
107
What is the clinical syndrome and treatments of Myaesthenia Gravis?
Weakness and fatigue is the clinical syndrome The treatment is: ACH inhibitor, Plasmaphersis, Thymectomy
108
List 3 connective tissue disease
ANCA vasculitis SLE Scleroderma
109
what is the autoimmune process of Scleroderma?
ANA cause vasculopathy with marked secondary fibrosis

Year 2 clinical pathology (21 decks)

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