Page 124 - Concise Pathology for Exam Preparation ( PDFDrive )

5 Diseases of Immunity 109

• �Most reliable technique to demonstrate ANAs is indirect immunofluorescence (IF)
which shows four basic patterns, namely:
1. Homogenous/diffuse nuclear staining: Antibodies to chromatin, histones and double

stranded (ds) DNA
2. Rim or peripheral staining patterns: Antibodies to ds DNA

3. Speckled pattern: Most common and least specific pattern. IF shows uniform- and

variable-sized specks, which indicate presence of antibodies to sm (Smith) antigen,
RNP (ribonucleoprotein), SS-A and SS-B
4. Nucleolar pattern: Most commonly seen in systemic sclerosis. IF shows discrete

spots in the nucleus which indicate antibodies to nucleolar RNA.
• �The fluorescence patterns are not absolutely specific for the type of antibody as there
can be more than one antibody or a combination of patterns.
• �Antibodies to Sm antigen and ds DNA are however virtually diagnostic of SLE.

• �Correlation between presence of certain ANAs and clinical manifestations is noted, eg,

high titers of ds DNA antibodies are found to be associated with active renal disease.

• �Antiphospholipid (AP) antibodies (antibodies against plasma proteins complexed

to phospholipids, eg, prothrombin, annexin V, b2 glycoprotein 1, proteins C
s
a
)
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and well antibodies against RBCs, platelets and lymphocytes may also be
a
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seen SLE.
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Pathogenesis of SLE

Pathogenesis of SLE is thought to be multifactorial.
• �Genetic factors
• �Increased risk in family members and concordance in monozygotic twins noted
• �MHC genes are thought to regulate the production of autoantibodies (specific poly-
morphisms of HLA-DQ are linked to the production of anti-ds DNA, anti-Sm and
AP antibodies)
• �Non-MHC genes may also contribute
• �Lupus patients may have inherited deficiency of early complement components;
eg, C2 (lack of complement impairs removal of circulating immune complexes)
• �The genome-wide association studies have indicated the involvement of several ge-
netic loci. These loci encode proteins which are responsible for lymphocyte activation
and cytokine (IFN) responses.
• �Environmental factors

• �Drugs such as hydralazine and procainamide are known to induce an SLE-like response.

• �Ultraviolet light may bring about changes in DNA such that it becomes immunogenic.
• �Sex hormones are thought to be involved in the pathogenesis (since females are
affected more than males).
• �Immunologic factors
• �Susceptibility genes interfere with normally existing self-tolerance. Environmental
insults induce apoptosis and defective clearance of the nuclei of the apoptotic bodies
which in turn increases the burden of nuclear antigens.
• �Self-nucleic acids may mimic their microbial counterparts to activate TLRs which
send signals to B cells specific for nuclear antigens as well as dendritic cells resulting
in production of antinuclear antibodies. Dendritic cells produce type 1 IFN which
stimulates B cells.
• �Tissue damaging antibodies are driven against self-antigens (results from an antigen-
specific helper T cell-dependent B cell response). The lesions of SLE are mainly
caused by immune complexes (type III HS).
Classification of SLE is given in Table 5.11.
4/11 criteria should be present for diagnosis of SLE.
Morphological Features of SLE
Most characteristic lesions result from deposition of immune complexes in the kidneys,
connective tissues and skin.
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