Laboratory Tests in Lupus

(alias Systemic Lupus Erythematosus)

These notes are based on a talk by a Consultant Immunologist at a North of England Hospital, as republished in "News & Views", Winter 2000.

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What is the purpose of blood tests?

Introduction

When you go to see the specialist, it seems to be an inevitable consequence that blood tests are taken at each visit and if you have lupus there are always lots of different coloured bottles. What are these tests and what do they tell the specialist? This article hopefully gives some greater insight into what happens behind the scenes.

There are many reasons for the tests. If it is the first visit then these will be for diagnosis. Once the diagnosis has been made blood tests will help identify the activity of the lupus, monitor for the development of complications such as kidney involvement, and help monitor for the side effects of the drugs used to treat lupus.

Diagnosis of lupus is not as easy as it might seem, because although quite strict criteria for lupus have been laid down, individual patients often do not have all the features and the features may change over time. The specialist will have a good idea about the diagnosis from the questions that he/she asks and from the findings in the examination. However, blood tests are essential to help confirm the diagnosis and the most important are discussed below.

What blood tests are done to help diagnose Lupus?

FULL BLOOD COUNT (Fbc)

This looks at the cells in the blood and detects anaemia, low platelets and low white blood cells in patients with lupus.

CREATININE AND ELECTROLYTES

This measures the salts in the blood and gives an idea of kidney function. If the kidney is failing then the creatinine, a waste product from the breakdown of protein in the body, starts to rise. Changes in the salts such as potassium can indicate a need for urgent treatment.

LIVER FUNCTION TESTS

These include measurement of liver enzymes, (which if raised can indicate liver cell damage) and albumin, which is the main protein in the blood: this falls if there is a kidney problem with leakage of the proteins into the urine [proteinuria].

INFLAMMATORY MARKERS

These include the ESR [sedimentation rate], which is a marker of non-specific inflammation and tends to be raised in lupus. Another marker is the CRP [C-reactive protein] which does NOT usually go up in lupus, but tends to go up if there is infection and thus helps the specialist decide whether there is infection present causing symptoms that might be mistaken for active lupus.

URINE TESTING

It is very important to test the urine in patients suspected of having lupus as this gives a good indication of the function of the kidneys. It is usually done first with dipsticks that measure protein and blood cells in urine [there should not be any!) More sophisticated tests can be done in the laboratory to identify 'casts', which are blobs of protein escaping from the bloodstream because the kidneys are leaky.

BLOOD CLOTTING TESTS

These tell how 'sticky' the blood is and include the lupus anticoagulant and antiphospholipid antibodies that are the hallmark of the Hughes syndrome, which is associated with recurrent miscarriages and clots in the blood vessels.

Immunological tests in the diagnosis of Lupus

These are the least well-understood tests. Antibodies are proteins produced by white blood cells [B lymphocytes] and their normal function is to glue up bacteria and make them easy for the white blood cells to capture and destroy. When the immune system goes wrong, antibodies can be formed that bind to bits of the body [an autoantibody]. Sometimes infection can cause auto-antibodies to be produced and this may be one of the causes of lupus. There are lots of different types of auto-antibodies.

Anti-nuclear antibody

This is a blanket term for lots of different antibodies that bind to the nuclei of cells, but not all types of anti-nuclear antibody are associated with lupus. The 'LE' cell is an old-fashioned test: it detected antibodies to histones [proteins that support the DNA in the genetic material of a cell]. Anti-histone antibodies are often found when the lupus is triggered by drugs. We do not now test for LE cells but use a direct test for antibodies to histones.

Antibodies to double stranded-DNA

These antibodies are very important in the diagnosis of lupus; they bind to the DNA [genetic material] in the nucleus of cells. It is very important to find these antibodies if a diagnosis of lupus is to be confirmed.

Anti-Sm antibodies

This is another antibody that binds to proteins in the nucleus of cells. It is rare in the UK and is mainly found in West Indians with SLE. It is not found in diseases other than SLE, so again it is very important in the diagnosis if it is found in the bloodstream.

Antibodies to ENA (extractable nuclear antigens)

These are other antibodies to proteins in the nuclei of cells, an include anti-Sm. Other important antibodies include anti-R [especially associated with lupus skin disease, sensitivity to the sun heartblock in new born babies and Sjogrens syndrome], anti-La [SLE Sjogrens syndrome], anti-RNP [if present with antibodies to DNA then diagnosis is SLE: if present alone, then diagnosis is undifferentiated connective tissue disease, UCTD].

Complement studies

The complement system of proteins in the blood is also importani in getting rid of bacteria. Deficiency of certain complemeni molecules increases the risk of developing SLE [especially C2, C4] these deficiencies run in families. Complement is also used up wher SLE is active, because of the damage to tissues; this can be measurec by C3d, a breakdown product of one of the main proteins.

Total antibody levels (serum immunoglobulins)

Normally these are high in SLE but occasionally may be low and this may lead to infections, as well as the other problems of lupus.

Other auto-antibodies

Lupus is associated with other autoimmune diseases, such as thyroid disease [over or underactive] and myasthenia gravis, a disease with weakness of the muscles.

Monitoring disease activity of lupus with laboratory tests

Regular blood tests are essential to monitor how active the disease is and whether treatment is working. Tests will include:

Monitoring for side effects of drugs

All drugs have side effects and drugs used to treat severe lupus have more than most. The specialist will therefore need to take regular blood samples to check for side effects.

Prednisolone and other steroids

Steroids have had a bad press recently, but still form a very important part of the treatment for lupus. They have many side effects and the doctors will keep a close check on the blood glucose [sugar], the fats in the blood and will do a full blood count [as the steroids are toxic to lymphocytes].

Azathioprine

This is an immunosuppressive drug that can damage liver and bone marrow, leading to very low white blood cell counts - regular liver enzymes and full blood counts to look at white blood cells will therefore be necessary, particularly when starting treatment. Antibodies can become very low in patients on azathiopnine for a long time. An enzyme test is now available that predicts whether side effects are likely with azathioprine [thiopurine methyltransferase - TPMT], and this will often be done before starting treatment.

Cyclophosphamide

This drug is very toxic to white cells, so regular full blood counts are essential. Antibodies can become very low and need checking from time to time. It can also cause bleeding from the bladder, although there is an antidote that prevents this, which is usually given with high doses of cyclophosphamide; the urine will be checked from time to time.

Cyclosporin & Tacrolimus (FKSO6)

These are very powerful immunosuppressives which can damage kidneys and liver, so it is important to check kidney and liver function regularly. Blood levels can be measured in the laboratory to help adjust dose safely.

Monitoring for the complications of Lupus

Kidney disease

This can develop very suddenly, so regular checks of kidney function are necessary, including urine tests.

Other Autoimmune diseases

Thyroid disease (under or over active] can be detected by blood tests for the levels of the thyroid hormones and for antibodies to the thyroid gland.

Myasthenia gravis

This is a disease in which auto-antibodies interfere with muscles and prevent the signals to move the muscles reaching the muscle from the nerves. The auto-antibody can be detected in the blood stream, although other types of tests are also required to confirm the diagnosis.

Blood problems

Low red blood cells, platelets or white cells may all occur both in lupus itself and as a result of the drugs used to treat the disease and it may be difficult to tell the difference! Nonetheless the specialists will be keeping a watch on the blood counts for unusual features or sudden changes.

Liver disease

This may occur as a result of lupus or from drugs used to treat it. Regular tests for liver enzymes required, but suspicion of liver disease may need to be confirmed by a biopsy [taking a tiny amount out under a local anaesthetic].

Summary

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©Andy Taylor. Last updated 13 Mar 2001