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represents a breakdown of the immune system’s ability
to discriminate between self and nonself
the body’s immune system becomes misdirected,
attacking the organs it was designed to protect
Involves either MHC class I or class II but most
especially class II
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Occurrence of an immune response resulting in the
production of either antibody and/or sensitized
lymphoid cells capable of reacting with normal body
constituents
All autoimmune diseases involve antigen-antibody
complexes (immune complexes)
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1. Release of sequestered antigens (hidden antigens;
recognized after trauma)
2. Self-antigens are slightly altered and the body makes
antibodies to these self-antigens
3. Cross-reacting (heterophile) or closely related
antibody
4. The spontaneous emergence of clones cells capable
of making immune response to one’s own tissues
5. Deficiency of T suppressor cells
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a. Increase serum gamma globulin
b. occurrence of different autoantibodies detected in
serum
c. decreased complement concentration in serum
d. absence of CD8+ lymphocytes
e. immunoglobulin and complement deposits in
arterial walls and basement membranes
f. lesions detected by biopsy
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Anti-nuclear antibodies
◦ Antibody produced to different components of the
nucleus during the course of several autoimmune
diseases
◦ Associated with systemic lupus erythematosus (SLE),
mixed connective tissue disease (MCTD), and
rheumatoid arthritis
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Anti-nuclear antibodies
◦ Techniques used: agglutination, indirect
immunofluorescence, and enzyme immunoassay
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Diffuse or homogenous: evenly stains the nuclei and is
associated with anti-DNA antibody and histones
◦ Solid, diffuse
◦ Characterizes:
Anti-deoxyribonucleoprotein (DNP) antibodies
(i.e. antibodies to nDNA, dsDNA, ssDNA, DNP or
histones)
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Diffuse or homogenous
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Diffuse or homogenous:
◦ Associated with:
Typically seen in rheumatoid arthritis
High titers of homogenous ANA are suggestive of SLE
Low titers may be found in SLE, RA, Sjogren’s
syndrome and Mixed Connective Tissue Disease
(MCTD)
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Peripheral: stains the edge of the nuclei and is associated
with anti-DNA antibody and anti-lamins (proteins found in
the nuclear membrane) antibody
◦ Ring, membranous, shaggy or thread
◦ Pattern results from antibodies to DNA
◦ Due to: Anti-dsDNA
◦ Associated with:
Active stage of SLE
Sjogren’s syndrome
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Peripheral
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Speckled: numerous evenly distributed stained
speckles within the nuclei associated with antibodies to
extractable nuclear antigens – nuclear
ribonucleoprotein (RNP) and anti- Smith (Sm)
◦ Pattern occurs in the presence of antibody to any
extractable nuclear antigen devoid of DNA or histone
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Speckled
◦ Due to:
Anti-extractable nuclear Ag (ENA)
Anti-Smith (Sm)
Anti-ribonucleoprotein (RNP): has been found in
patients with wide variety of rheumatic diseases
including SLE, RA, Sjogren’s syndrome, progressive
systemic sclerosis, MCTD and dermatomyositis
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Speckled
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Nucleolar: stains two or three large fluorescent areas
within the nucleus and is associated with anti-RNP
antibody
◦ Reflects: Antibody to nucleolar RNA
◦ Present in about 50% patients with scleroderma
(progressive systemic sclerosis), Sjogren’s syndrome
and in SLE
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Nucleolar
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Centromere: stains as a discrete speckled pattern due to
anticentromere antibody
◦ Antibody reacts with the centromeric chromatin of
metaphase and interphase cells
◦ Due to:
Anti-centromere antibody (ACA)
◦ Appears to be highly selective for CREST variant of
progressive systemic sclerosis
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Centromeres
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Rheumatoid factor
◦ Rheumatoid factor (RF) is an anti-antibody, typically
IgM, that binds to the Fc portion of abnormal IgG
◦ Also, noted in chronic hepatitis, SLE and syphilis.
Cryoglobulins
◦ Proteins that reversibly precipitate at 4°C
◦ Associated with autoimmune diseases such as
vasculitis, glomerulonephritis, SLE, RA, and Sjogren’s
syndrome
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Chronic inflammatory autoimmune disease
characterized by the presence of ANA
Symptoms may include swelling of the joints,
erythematous rash and deposition of immune
complexes in the kidneys
• Pathologic features:
➢ chronic, inflammatory, multiorgan disorder
➢ butterfly rash
➢Renal involvement
➢ CNS manifestations
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Laboratory diagnosis of SLE
◦ 1) Demonstration of LE cell
Neutrophil has engulfed the antibody-coated nucleus of
another neutrophil
◦ 2) Detection of antinuclear antibodies
ds-DNA antibodies : Most specific to SLE this can be
detected by FANA, Crithidial and RIA testing.
Anti-histone antibody: Drug induced Lupus
Anti-Sm antibody: Specific for Lupus because it is not
found in any other autoimmune diseases but only 7- 25%
with Lupus is positive with the antibody.
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Laboratory diagnosis of SLE
◦ 1) Demonstration of LE cell
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Autoimmune disease that affects the synovial
membrane of multiple joints
Characterized by the presence of an autoantibody
called rheumatoid factor (RF)
Pathologic features:
◦ chronic, inflammatory joint disease with lesions
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Laboratory diagnosis of RA: Based on the detection of
RF
◦ 1) Sheep cell agglutination test: Rose-Waaler Test à
tannic acid-treated sRBCs are coated with rabbit IgG
◦ 2) Latex fixation test: Singer and Plotz
◦ 3) Sensitized alligator erythrocyte test: Cohen et.al
◦ 4) Bentonite flocculation test: Bloch and Bunim
◦ Note: Anti-cyclic citrullinated peptide antibody (anti-
CCP)
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An inflammation of salivary and lacrimal glands
causing dryness of mouth and eyes
Pathologic features:
◦ chronic inflammatory disease: exocrine glands
◦ patients have dry eyes, dry mouth, dry nose, larynx
and bronchi
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Laboratory findings
◦ Polyclonal hypergammaglobulinemia;
◦ autoantibodies against the salivary glands;
◦ positive RF,
◦ ANA (speckled or diffuse pattern), anti-SSA, and
anti-SSB
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Increased rate of RBC destruction
Results in normocytic, normochromic anemia
Autoantibody is directed against RBC antigens
Laboratory findings
◦ positive direct antiglobulin test
◦ sometimes cold agglutinins
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