week 3 Autoimmune disease and diagnosis Flashcards Preview

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Flashcards in week 3 Autoimmune disease and diagnosis Deck (109)
1

what is the definition of sensitivity?

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

2

what is the definition of specificity?

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

3

what is the definition of Positive predictive value ?

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

4

what is the definition of negative predictive value ?

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

5

Give a example of a non specific diagnostic test?

Inflammatory markers

6

Give a examples of a disease specific diagnostic test?

Autoantibody testing

HLA typing

7

what is erythrocyte sedimentation rate (ESR)?

old way of measure the inflammation in the serum

8

how does ESR work?

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

9

What is C reactive protein when is it produced?

liver produces after acute phases of systemic inflammation of the liver

10

how is CRP used ?

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

11

give example of Non-specific markers of systemic inflammation?

Erythrocyte sedimentation rate (ESR
CRP
Ferritin
Fibrinogen
Haptoglobin
Albumin
Complement

12

what does low albumin in the blood mean?

liver disease/damage

13

What happens to levels of ferritin and fibrinogen in inflammation?

Increase in acute inflammatory response

14

What are Antinuclear Ab? (ANA)

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

15

What is meant by Extractable nuclear antigens (ENAs)?

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

16

how do you detect ANA?

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

17

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

Peripheral or homogenous

18

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

Homogenous

19

what are the techniques to detect ENA's?

Immunoblots
Individual ELISA’s
Combination of antigens

20

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

To particular connective tissue disorders
Including Systemic lupus erythematosus SLE

21

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

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

22

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

Anti-ds DNA
High specificity for SLE --> often correlates with high active severe disease

23

what is RF?

It is a antibody directed against the Fc portion of IgG

24

When is RF found?

Commonly found in rheumatoid arthritis

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