Complement components C3 and C4 are measured to help diagnose and monitor systemic lupus erythematosus (SLE). Low levels of C3 and C4 indicate activation of the classical complement pathway and an active SLE flare, while low C4 with normal C3 could indicate a genetic deficiency. The antinuclear antibody (ANA) test screens for autoantibodies that target nuclear antigens and is positive in 95% of SLE cases, though it is not specific to SLE. Additional tests for extractable nuclear antigens (ENA) like anti-Sm and anti-dsDNA antibodies can help determine the specific autoimmune disease when ANA is positive. The anti-dsDNA antibody test in particular helps diagnose SLE when A

1. The significance of C3 and C4 in SLE
investigation:
• Complement is a part of immune system that fights infection, or in the
case of Lupus it can attack body’s own cells.
• Measurements of serum complement components C3 and C4 are useful in
the diagnosis and monitoring of immune complex disease(SLE) and it can
indicate the activity of the disease.
Serum C3 and C4 level
Low C3 and
C4
classical pathway
activation
(active SLE and
current flare)
Normal C3
and Low C4
genetic C4
deficiency
Low C3 and
persistent
lowC4
alternative
pathway
activation
(renal flare
involves)
Normal C3
and C4
SLE disease
is more likely
calm
flare is : A measurable
increase in disease
activity in one or more
organ systems involving
new or worse clinical
signs and symptoms
and/or lab
measurements.

2. ANA are a group of autoantibodies produced by a person's immune
system when it fails to adequately distinguish between "self" and
"nonself."
ANA specifically target substances found in the nucleus of a cell, ,
hence the name "antinuclear. ANA can cause damage to tissue by
reacting with nuclear substances when they are released from
injured or dying cells.
Antinuclear antibodies (ANA) test in
case of SLE

3. The ANA test is an indirect fluorescent antibody
procedure for the detection and semi-quantitation of
human antinuclear autoantibodies.
The ANA test principle:
Human epithelial (HEp-2) cells are used for this test.
Observation of a specific pattern of fluorescence on the
HEp-2 cells indicates the presence of autoantibodies in the
patient's serum. Titers are done on positive specimens.

4. Method used for The ANA test :
indirect immunofluorescence (IF).

5. Interpretation of the ANA test results :
The test for antinuclear antibodies (ANA) is a good screening test
for autoimmune disorders.
A positive ANA test autoantibodies are present
95% of patients with systemic lupus erythematosus (SLE) will have
a positive ANA test using human HEp-2 cells.
However, a positive ANA result is not specific, positive test result can
also mean that you have one of these other autoimmune diseases:
• Sjögren's syndrome
• Scleroderma
• Rheumatoid arthritis
• Polymyositis
ANA test can't confirm which exact one the patient have. If ANA test
is positive, confirmatory tests should be done.

6. -To determine specificity of Abs that have produced +ve
ANA .
- first qualitative method (immunoblot), then confirm
with ELISA.
-In immunoblot there are multiple Ags:
1) SSA/Ro60→ neonatal lupus
2) SSB → neonatal lupus
3) Ro52 → neonatal lupus
4) Sm → SLE
5) Jo1 → polymyositis (interital lung disease)
6)nRNP → diagnosis of mixed connective tissue disease
ENA (extractable nuclear antigens)test

7. .Muscle pain
.Arthritis-like pain in one or more joints
.Red rash that frequently resembles a butterfly .
.Low-grade fever
.Persistent fatigue, weakness,Hair and weight loss
anti-double stranded DNA (anti-dsDNA) test is used to
help diagnosis of lupus (systemic lupus erythematosus,
SLE) in a person who has a positive result on a test
for antinuclear antibody (ANA) specially when the result
of the ANA test presents as a "homogeneous" or
"speckled" fluorescent pattern and has clinical signs and
symptoms that suggest lupus.
anti-double stranded DNA (anti-dsDNA) test
in case of SLE

8. anti-dsDNA test may be ordered along with a test
for anti-Sm (Smith antibody), another antinuclear
autoantibody associated with lupus, to help
establish a diagnosis.
Anti-dsDNA tests may be performed using
different assays. Many laboratories use an anti-
dsDNA ELISA test (enzyme-linked
immunoabsorbent assay), but other methods may
also be used.

9. An increased anti-dsDNA level may
be seen prior to and during these
flare-up
in which symptoms worsen and
then subside
A very low level of anti-
dsDNA is considered
negative but does not
exclude a diagnosis of
lupus.
used to monitor lupus nephritis:
a serious complication of lupus that
can cause kidney damage and
inflammation.
This can lead to protein in the
urine, high blood pressure,
and kidney failure.
It occurs when the autoantibodies
bind to antigens that have been
deposited in the kidneys.