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26th February 2025
Investigations in SLE
Full blood count can show decreased white blood cells, lymphocytes or platelets. ESR increases with disease activity, whereas CRP classically does not, and so a raised CRP suggests another cause for symptoms such as infection.
Antinuclear antibodies are the hallmark of serological diagnosis of SLE, although can be nonspecific. Around 10% of healthy individuals will have low-titre ANA positivity, which is of no consequence if not accompanied by relevant clinical features (Box 1). Conversely, there can be very rare cases of ANA-negative SLE, although this occurs in less than 5% of cases. Other autoantibodies may be found and are correlated with specific clinical features (Table 2).
Additionally, reduced levels of C3 and C4 are common in SLE, and often correlate with increased disease activity. Furthermore, hereditary deficiencies of the classical complement pathway (C1q, C1r, C1s, C2, C4) can cause SLE.
| Autoantibody | Association | Comment |
|---|---|---|
| ANA | >95% positivity rate in SLE | |
| dsDNA | Lupus nephritis | If positive, correlates with disease activity |
| Sm | Renal and neurological disease | Most specific, however only positive in up to 30% patients |
| Ro/SS-A | Sjögren’s overlap
Neonatal heart block Cutaneous neonatal lupus |
|
| La/SS-B | ||
| U1 RNP | Mixed connective tissue disease | |
| Histone | Drug-induced lupus | |
| Antiphospholipid antibodies | Thrombosis
Pregnancy loss |
There is a common overlap between antiphospholipid syndrome and SLE |
Table 2 Autoantibodies in SLE and their associated clinical features.
| ANA testing
Indirect immunofluorescence is used to test for ANA, and the tests are repeated at serial dilutions until fluorescence is no longer detected. Therefore, the higher the second number in the ratio, the ‘stronger’ the positive result, as it is present at a higher dilution factor. The starting dilution used varies in different laboratories, but around 1:80 tends to be the first dilution used – therefore, this is the ‘weakest’ positive ANA. ANA is positive at 1:80 titre in around 10% of the population. Given the 1% prevalence of ANA-positive rheumatic disease in the general population, there is a large number of false positive ANA results. Different staining patterns can also be seen, which can be associated with certain underlying autoimmune diseases and autoantibodies; however, they are not specific. Patterns include homogenous staining, associated with histone proteins, speckled staining, associated with U1 RNP and Sm antibodies, centromere staining, associated with limited cutaneous systemic sclerosis; and nucleolar staining, associated with multiple rarer autoantibodies. |
Box 1 ANA testing and significance
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