DR. CORA LIM-MEDICAL INSIDER
Systemic Lupus Erythematosus
PART 3
Let us continue with our discussion of
Systemic Lupus Erythematosus.
Immunology
Studies say that SLE is the result of
multiple defects in both the innate and
adaptive immune system with altered
immune tolerance, hyperactivation of T-
and B-cells, reduced ability to clear immune
complexes and apoptotic cells and the
failure of multiple regulatory mechanisms
within the immune network.
Furthermore, the same studies say that
there is abnormal release of intracellular
antigens, for example because of
dysregulated apoptosis.
A loss of B-cell self-tolerance results in
excessive autoantibody production with
immune complex mediated type III
hypersensitivity reactions.
I has to be noted that immune complex
deposition within tissues leads to
complement activation, inflammatory cell
recruitment and tissue damage.
It should be noted, further, that innate
immune cells are recruited and produce
pathogenic cytokines, such as interferon
alpha, tumour necrosis factor and
interleukin-1 with abnormal type-1
interferon regulation. B-cell involvement,
independent of antibody production, may
also occur through antigen presentation, T-
cell activation and dendritic cell modulation.
The same findins say that T-cells also
contribute to autoimmunity in SLE with
defects associated with CD8+ and T-
regulatory cell function occurring along with
an expanded CD3 + CD4 – CD8 – T-cell
lineage.
Serology
Let us discuss the serology of this matter.
Antinuclear antibodies (ANA) are the
hallmark serological feature of SLE, with
the majority (>95%) of patients having a
positive ANA at some point during their
disease course.
Therefore, there are declarations that ANA
is a useful screening test for SLE. There is
a strong consensus that the presence of
autoantibodies is essential to make a
diagnosis of SLE. Enzyme-linked
immunosorbent assay (ELISA) tests are
increasingly used to test for ANAs but this
has a higher risk of a false negative result.
A negative ANA on ELISA in a patient with
a strong clinical suspicion of SLE should be
followed by repeat testing with indirect
immunofluorescence to Hep2 cells. ANA
negative patients are unlikely to
demonstrate positive extractable nuclear
antigen (ENA) tests.
Studies also have it that false positive ANA
results are common secondary to infection
or other autoimmune disease. A modestly
raised ANA titre may also be seen in
individuals with no discernible disease.
Therefore, a positive ANA result should
precipitate testing for anti-double stranded
DNA (anti-dsDNA) antibodies and
antibodies to specific ENAs such as anti-
Ro, anti-La, anti-Sm,anti-RNP. Anti-Ro and
anti-La antibodies occur in around 30% and
20% of patients with SLE, respectively,
although they are more common in
Sjögren’s syndrome.