Feeling constantly exhausted, living with aching joints, or developing unexplained rashes can be frustrating—especially when the cause isn’t obvious. Your GP will usually begin by ordering routine blood tests, including inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).
Think of CRP as a smoke alarm. A raised CRP tells your doctor that inflammation is happening somewhere in the body, but it doesn’t identify the cause. An infection, injury, or autoimmune disease can all produce a high CRP.
To identify whether the immune system is mistakenly attacking your own body, doctors often order autoantibody blood tests. These tests look for specific antibodies linked to particular autoimmune diseases and help narrow down the diagnosis.
Normally, antibodies protect you by recognising viruses and bacteria.
In autoimmune diseases, the immune system becomes confused and produces autoantibodies that attack healthy tissues instead.
Inflammatory markers such as CRP and ESR measure the body’s response to inflammation, whereas autoantibody tests look for the specific immune proteins responsible for triggering that inflammation.
Main use: Screening for systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE).
What it measures
ANA detects antibodies directed against the nucleus of your body’s own cells.
What a positive result means
A positive ANA may be seen in:
However, ANA is not diagnostic on its own. Up to 15% of healthy people can have a positive ANA without having an autoimmune disease. If ANA is positive, further antibody testing (such as Anti-dsDNA or Anti-Smith antibodies) is usually performed.
When to worry
When to see a doctor
Main use: Supporting the diagnosis of rheumatoid arthritis (RA).
What it measures
RF detects an antibody that targets other antibodies, contributing to chronic inflammation within joints.
What a positive result means
A positive RF increases the likelihood of rheumatoid arthritis but is not specific. It may also occur with:
Some people with rheumatoid arthritis never develop RF (seronegative RA).
When to worry
When to see a doctor
Main use: A highly specific test for rheumatoid arthritis.
What it measures
Anti-CCP detects antibodies against citrullinated proteins, which commonly develop in rheumatoid arthritis.
Why it matters
Anti-CCP is much more specific than RF. A positive result in someone with inflammatory joint symptoms strongly supports a diagnosis of rheumatoid arthritis.
These antibodies may appear years before permanent joint damage develops, allowing earlier treatment.
When to worry
When to see a doctor
Main use: Diagnosing vasculitis, where inflammation damages blood vessels.
What they measure
ANCA antibodies attack certain white blood cells, leading to inflammation of blood vessel walls.
Associated conditions
ANCA testing helps diagnose several forms of vasculitis and can also identify autoimmune kidney inflammation (e.g. rapidly progressive glomerulonephritis, RPGN).
When to worry
When to see a doctor
Main use: Identifying autoimmune thyroid disease.
Anti-TPO antibodies
High levels suggest Hashimoto’s thyroiditis, the most common autoimmune cause of an underactive thyroid.
Symptoms may include:
TRAb antibodies
TRAb antibodies cause Graves’ disease, leading to an overactive thyroid.
Symptoms may include:
When to worry
When to see a doctor
Main use: Screening for coeliac disease.
What it measures
This test detects antibodies produced when someone with coeliac disease eats gluten.
Important before testing
Continue eating gluten before the blood test. Removing gluten beforehand can cause antibody levels to fall, leading to a false-negative result.
When to worry
When to see a doctor
Main use: Supporting the diagnosis and monitoring of systemic lupus erythematosus (SLE).
What it measures
Anti-double stranded DNA (Anti-dsDNA) antibodies target the genetic material (DNA) found inside the nucleus of cells.
What a positive result means
Anti-dsDNA is much more specific for lupus than ANA. A positive result, particularly alongside a positive ANA and symptoms suggestive of lupus, strongly supports the diagnosis.
Higher antibody levels may also be associated with increased disease activity, especially lupus nephritis (kidney inflammation).
When to worry
When to see a doctor
Main use: Confirming systemic lupus erythematosus (SLE).
What it measures
Anti-Smith antibodies target proteins involved in processing genetic material inside cells.
What a positive result means
Although Anti-Smith antibodies are present in only a proportion of people with lupus, they are highly specific. A positive result strongly supports the diagnosis when symptoms are consistent with SLE.
Unlike Anti-dsDNA, Anti-Smith antibody levels are not generally used to monitor disease activity.
When to worry
When to see a doctor
Main use: Helping identify specific connective tissue diseases after a positive ANA.
What it measures
The ENA panel includes several autoantibodies, such as:
Each antibody is associated with different autoimmune conditions.
What a positive result means
Depending on which antibody is detected, the ENA panel may support diagnoses such as:
The results are interpreted alongside symptoms, examination findings, and other blood tests.
When to worry
When to see a doctor
Main use: Diagnosing primary biliary cholangitis (PBC), an autoimmune disease affecting the bile ducts in the liver.
What it measures
AMA detects antibodies directed against structures within mitochondria, the energy-producing components of cells.
What a positive result means
A positive AMA strongly suggests primary biliary cholangitis, particularly when liver blood tests show a raised alkaline phosphatase (ALP).
Early diagnosis allows treatment that can slow disease progression and reduce the risk of liver damage.
When to worry
When to see a doctor
Autoimmune diseases often develop gradually, and many symptoms overlap with common illnesses. Speak to your GP if you experience several of the following together:
Butterfly rash of lupus. Note vasculitic lesions on lips
Arrange an appointment with your GP if your symptoms persist, recur, or begin affecting your daily life.
Remember that no single blood test can diagnose an autoimmune disease on its own. Your doctor will interpret the results alongside your symptoms, physical examination, medical history, and, if needed, imaging or additional investigations.
If an autoimmune condition is suspected, you may be referred to a specialist such as a rheumatologist, endocrinologist, gastroenterologist, or nephrologist.
Early diagnosis and treatment can significantly reduce inflammation, prevent long-term organ damage, and improve quality of life.
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