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1. Autoimmune disease

2. •Def: can be define as the presence of
immune response against self-targets, and is
to some extend ubiquitous
•it may be harmless phenomenon, identified
by the presence of low titre autoantibody or
autoreactive T-cells.
•Autoimmune dis. Occur if these responses
cause significant organ damage.
•These are major cause of chronic morbidity
and disability, affecting up to 1 in 30 adults at
some time.
5250
-50

3. Physiology and pathology
•Immunological tolerance
•This is the process by which the immune system distinguish between self
and foreign tissue
•Central tolerance occurs during lymphocyte development and operates
in the thymus and bone marrow, this process is more active in fetal life
and continues through out life as immature lymphocytes are generated
•Peripheral tolerance mechanism which occurs when autoreactive cells
escape into the peripheral circulation, it include suppression of
autoreactive cells by regulatory T-cell and generation of
hyporesponsiveness (anergy)
•Anatomical posture also play role in immunotolerance like in eye
•Failure of any of these tolerance mechanism may result in the
development of autoimmune dis.
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4. Factors predisposing to autoimmune
disease
Genetic factors:
•HLA genes
•Genes that regulated cytokines production and function,
co-stimulation and cell death
Environmental factors that genetically suitable patient :
•Infection like in post-streptococcal rheumatic fever ??
Can be explained in many theories like what’s called molecular mimicry or
it may provoke the production of inflammatory cytokines that may
overwhelm normal control mechanism .
•Drugs side-effect e.g. halothane
•Note: F/M ratio are very high for unknown reason
A low F/M ratio means there are
many microorganisms and a
limited food supply. Conversely, a
high F/M ratio means there is
much more food available
compared to microorganisms.
= dis
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foodto
microorganism
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6. Classification of autoimmune disease
•Organ specific
•Multisystem

9. Investigation
•Autoantibody
Antibody is quantified either by titre ( the minimal dilution at which the antibody
can be detected) or by concentration in standardized units.
• rheumatic factor:
-antibody directed against the common (Fc) region of human IgG.
-IgM is most commonly tested
-titre > 1/40 or unit value > 20 U is consider positive, relay on method.
-only 50 % with positive RF patients are diagnosed as Rheumatoid arthritis in
addition to 25% in the 1
st
2 years(seropositive)
-low sensitivity and low specificity (insufficient)
-associated with wide range of auto and no autoimmune dis. And a common finding
in elderly
- Major indication for RF to evaluate prognosis in RA,as its ass. With more sever
erosive dis.and extra-articular dis manifestation like nodules,vasiculitis

10. Anti-CCP antibody
•Antibodies to cyclic citrullinated peptide
•Bind to peptide in the amino acid arginine converted to
citrulline by peptidylarginine deiminase an enzyme abundant
in inflammed synovial tissue
•More specific test for RA than RF and better predictor of an
aggressive course
•In patient with undifferentiated arthritis can differentiate
those who can develop RA
cyclic citrullinated peptide-

11. Antinuclear antibody
•ANA are group of antibodies which bind to component of the nucleus
•They are detected by applying serum to human cell line (Hep 2 cells)
followed by immunofluorescence Microscope.
•Antibody titre > 1:80 is usually considered positive with this method.
•Pattern of immunofluorescence reflects binding discrete nuclear
components, specific pattern may be ass. With clinical subgroup e.g. rim
pattern ass. With SLE, nuclear staining seen in diffuse scleroderma
•The major indication for ANA is in the Dx of SLE (100% sensitivity)
•Generally the specifity is low
•5% of healthy person have an ANA titre 1:80
•There is no role for ANA in follow up the prognosis
•Used in the Dx of most of CTD like scleroderma,SLE,dermatomyositis..etc
congenital thymic dysplasia
&
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12. Antibody to extractable nuclear antigen
•When ANA positive, then it will be useful to determined which nuclear
component antigen being recognized
•Some nuclear antigen are soluble and can be extracted from the nucleus
•Antibody to these antigen have high specifity for individual dis. subgroup
•Sensitivity is low
•There is little value in testing for antibodies to extractable nuclear antigen
if the ANA is negative.
•Those like anti-centromere antibody(CREST variant of scleroderma),
antihistone antibody(drug induced lupus), anti-smith antibody(SLE) …etc

15. AntiDNA antibody
•Bind to double stranded DNA and highly specific for SLE (95%)
•They occur in up to 60% of SLE patients at some time in their
dis. Course, very high titre more ass. With sever dis. Including
renal or CNS involvement
•Useful in follow up of the dis. Process (prognosis and relapse)
•Antibody to SSDNA are nonspecific and have little clinical
application

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strand
DNA
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16. Antiphospholipid antibody
•Are ass. With the development of venous and arterial thrombosis
recurrent fetal loss
•This may occur in isolation (primarily antiphospholipid syndrome) or as
complication of SLE (secondary antiphospholipid syndrome)
•APA can also be detected in wide variety of RA,infectiuos and malignant
conditions when not usually ass. With thrombosis
•Anticardiolipin antibody and lupus anticoagulant are the freq.. Measured
•Anticardiolipin antibody are Immunoglobulin directed against
phospholipid particularly beta 2 glygopr-1
•The target of the lupus anticoagulant are prothrombin and occasionally
beta 2 glygopr-1
•If there is clinical suspicion of the dis. both antibodies should be
performed, lupus anticoagulant cant be done if patient on aspirin.
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17. Anti-neutrophill cytoplasmic antibody
•ANCA are IgG to the cytoplasmic constituent of granulocytes
•Two common pattern are describe in ass. With vasiculitis syndrome these
are:
a: cytoplasmic fluorescence (c-ANCA) is ass. With antibody to proteinase-3
(PR3), and occur in more than 90% of patient with Wegener’s
granulomatosis with renal involvement, and with some what lower
sensitivity in patient with limited Wegener’s granulomatosis
B: perinuclear staining pattern(p-ANCA) is ass. With antibody to other
cytoplasmic enzymes, particularly myeloperoxidase(MPO), lactoferrin and
elastase, positive p-ANCA alone is nonspecific but, if it s du to MPO it may
ass. With microscopic polyarteritis and Churg-struss vassiculitis, atypical
p-ANCA which not du to MPO antibody are commonly found in patient
with ulcerative colitis and autoimmune liver dis.but not DX nor
prognostic, serial measurement of anti -PR3 or anti-MPO antibody may be
useful for dis. Monitoring.
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18. Measurement of complement activation
•Useful in immune complex mediated disease
•Low C4 and C3 level indicates classical pathway activation
•Serial measurement of C3 and C4 is used for monitoring of
SLE

19. Cryoglobulinaemia
• Def: immunoglobulins that form precipitates in the cold.
•Classify into three types on the bases of the properties of
immunoglobulins
•Testing for cryoglobulinaemia require transport of a serum
specimen to the lab. At 37 centigrade
•Clinical management involve avoiding of cold and treating
underlining pathology
•Type 2 and type 3 may response to immunosuppression
and/or plasmapheresis to remove the pathogenic antibody
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20. Classification of cryoglobulinaemia
Type 1 Type 2 Type 3
Immunoglobulin Monoclonal IgM Monoclonal IgMPolyclonal IgM
Prevalence 25% 25% 50%
Disease associationLymphproliferative
disease
Infection,HBV,HCV
lymphproliferative
RA,SLE,
Infection,HBV,HCV
symptoms Hyperviscosity,rayn-
aud’s phenomenon
Acrocynosis
Small vessels
vasiculitis,pururic
rash,arthralgia
Small vessels
vasiculitis,pururic
rash,arthralgia
Protein
electrophoresis
Monoclonal IgM
praprotein
Monoclonal IgM
praprotein
No
RF Negative Strongly positive Strongly positive
Complement Normal Decrease C4Decrease C4
Serum viscosityRaised Normal Normal
heptiticB
,
c
virus
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