Current Diagnostic Methods for Autoimmune Disease
Author: Holly Young
Autoimmune disease (AD) is a condition in which the immune system mistakenly attacks healthy body cells. There are more than 80 different types, many of which share similar symptoms including fever, fatigue, headaches, joint stiffness, swelling, weight loss and numbness (figure 1). These symptoms are relatively common across a broad range of illnesses and can come and go (1,2).
Over £13 billion per year are spent on autoimmune conditions; this only accounts for type 1 diabetes, rheumatoid arthritis and multiple sclerosis. In 2018, it was estimated that around 4million people in the UK had an autoimmune condition and expected to grow by around 3-9% per year depending on the condition (3).
As AD present itself differently between patients this makes it difficult to diagnose especially as there is no one test capable of diagnosing many types distinctively: taking on average 5 years to achieve an accurate diagnosis (1,4)
Figure 1: Common symptoms in different autoimmune diseases (5).
The most common and effective diagnostic tests are laboratory tests that detect inflammatory response analytes.
Antinuclear Antibody (ANA) Test
Antibodies are proteins produced by the immune system to defend against foreign bodies such as viruses and bacteria but autoantibodies like ANA attack healthy cells of the body by targeting their nucleus.
ANA testing is carried out initially on suspicion of AD but cannot be used alone to identify a specific AD. If ANA levels are detected higher than normal and of concern, further testing will be carried out for a more definitive diagnosis. The main use for ANA testing is for systemic lupus erythematosus (SLE) diagnosis, 85% of those diagnosed with SLE had positive ANA results (1).
ANA testing has a high sensitivity but low specificity. False positives can occur in non-autoimmune conditions; more frequently in women over 65 and patients suffering from infections such as mononucleosis. A negative ANA test result does not rule out AD altogether. If a patient exhibits symptoms of AD, further testing is carried out (7).
Misdiagnosis can lead to many patients being wrongly diagnosed with SLE resulting in mistreatment with potentially toxic treatments. Highlighting further cause for advanced testing methods to be used in conjunction or replace current methods to improve the diagnostic process and produce more accurate and reliable results (8).
C-reactive protein (CRP) levels
CRP is a protein component of the blood produced by the liver in response to inflammation, the measurement of CRP test most commonly follows ANA testing (1). CRP levels are thought to reflect the body’s current inflammation state well. As CRP is relatively stable, it allows tests to detect even low levels of inflammation present: this has proved vital in analysing cardiac diseases and other inflammatory states (9).
Figure 3: CRP levels and the associated diseases in each category (9).
Various factors can make CRP levels difficult to analyse and interpret such as medication, minor injuries/infection, and chronic conditions. CRP testing is carried out alongside other tests to obtain a more in-depth diagnosis: CRP tests also tend to be repeated over a period to evaluate any changes (10).
Erythrocyte Sedimentation rate (ESR)
ESR measures the rate red blood cells (RBC) collect at the bottom of a test tube containing a blood sample. Normally, RBC settles relatively slowly but in AD the rate is faster than normal. Inflammation causes an increase in the ESR as it causes RBC to clump together, making them denser and therefore, they will sink to the bottom of the test tube more rapidly (11).
Routine Blood Tests
Blood tests are extremely valuable in the diagnosis and monitoring of AD. Common blood tests, including basic metabolic panel and complete blood counts, can measure the body’s metabolisms, blood component levels and abnormalities. Although abnormalities are not specific indicators of AD, they can provide a basis for further testing to be carried out (1).
Current advances in POC testing for autoimmune disease diagnosis
There have been advancements to improve diagnostics testing in some autoimmune conditions including diabetes and rheumatoid arthritis (RA).
Point of care (POC) testing to detect haemoglobin A1c (HbA1c) for diabetes is thought to have several advantages over standard laboratory testing but there are still some issues surrounding its accuracy (12). A lateral flow POC test for rheumatoid arthritis has also been developed. The test only requires a drop of blood, no specialist equipment and results in 15 minutes -some of the many advantages this test offers. It is also a critical development as RA can be difficult to diagnose in the early stages however, this is when major joint damage and loss of function tend to occur at their highest rate (13).
The ongoing COVID-19 pandemic has provided a greater insight into the involvement of autoantibodies and inflammation in the virus. A study found that at least one type of autoantibody was present in half of those who had been hospitalised with a severe case of COVID-19. Blood samples taken from individuals on admission and at various points during their recovery revealed that 20% of people did not have autoantibodies present when first admitted. But during their hospital stay and progression of the COVID-19 virus, they developed autoantibodies (14).
Conclusion
Most current testing methods for autoimmune disease are useful but cannot be used alone; they must be repeated and used in conjunction with other tests to provide a basis for an accurate diagnosis. This is one of the major factors leading to the diagnosis being complicated and usually taking many years to find answers. Advances in our knowledge and rapid, cost-effective, reliable POC testing for AD could shorten diagnosis time and greatly improve the process and in turn, improve treatment options (2).
References:
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