Many autoimmune diseases are characterized by the presence of antibodies to normal proteins. For example, in rheumatoid arthritis (RA), it’s typical to see antibodies to citrullinated peptides. In Systemic lupus erythematosus (SLE), antibodies to double-stranded DNA and other nuclear proteins are hallmarks of the disease.
Physicians use these different antibody reactivity patterns to distinguish autoimmune diseases, such as SLE from Sjogren’s syndrome or mixed connective tissues disease (MCTD). While these antibodies are critical to diagnosis, they can be a source of frustration for patients who experience the symptoms of a disease but cannot be “officially” diagnosed until the proper antibodies are detected.
Autoimmune disease is often present when antibodies are not measurable.
An Alternate Method for Detecting Autoimmune Disease
We tested samples from our extensive collection of plasma from autoimmune donors to look for other biomarkers of disease. We used the Vascular Injury panel from Meso Scale to measure the acute phase proteins, C-reactive protein (CRP), and Serum Amyloid A (SAA). These two proteins typically increase 10 or even 100 fold early in an inflammatory response.
Two other biomarkers in the panel, ICAM-1 and VCAM-1, are proteins expressed on the surface of cells lining blood vessels. Soluble forms of these proteins are found in the serum and plasma of individuals with injury to blood vessels.
We tested three groups of plasma samples: One group of donors with RA, one group with SLE, and a third group with a variety of autoimmune and allergic diagnoses. The RA samples had a higher CRP level than the other two groups, although there were outliers (See Figure 1). SAA levels were similar between the three groups (See Figure 2). The same donors who exhibited high CRP levels also expressed higher SAA values.
The SLE donors expressed a higher median level of VCAM-1 and ICAM-1 vascular injury markers than the other two groups (See Figures 3 and 4); a marked difference compared to the acute phase protein results above. This reflects the tendency of patients with SLE to experience damage to their vasculature whereas patients with RA typically experience joint damage.
The data above demonstrates that there is more than one way to monitor damage in autoimmune disease. When autoantibody levels are undetectable, look for other measures of disease activity, such as acute phase proteins, CRP, SAA, and surface-level proteins.
These disease processes can be challenging to monitor, so take advantage of all the tools at your disposal to gain a clearer picture. If you need access to our technology and tools, inquire about our research service capabilities.