By Kathryne Marks
Why are biomarkers important?
Looking for certain markers in a blood sample is a method that is helpful in the diagnosis many conditions, including Rheumatoid Disease (RD) and other autoimmune diseases. These biological markers—biomarkers— are increasingly helpful as we work to get to earlier and earlier diagnoses in order to hopefully get people treatment sooner—even before obvious symptoms—to improve outcomes.
There are a few different markers to know about, the most important of which are antibodies. Antibodies are produced by B cells, one of the most important types of cells of the adaptive immune system. Each B cell produces antibodies that are specific for, or capable of binding to, a particular other molecule. You don’t need to be an immunologist to understand why it is essential to identify these antibodies.
What are some key antibodies in RD?
There are two main groups of antibodies that are observed in people with rheumatoid disease: ACPAs and RF.
ACPA stands for anti-cyclic citrullinated peptides antibodies, which means antibodies that bind to particular citrullinated peptides. Citrullination is a process of replacing an arginine with citrulline in a protein, a process that often occurs during inflammation. The immune system of people with RA then considers these proteins foreign and creates antibodies against them that contribute to the auto-inflammatory process. So far we know that antibodies are made against citrullinated collagen, vimentin and fibrinogen among other peptides. ACPAs are found in the serum of up to 91% of people with RD / RA, depending on the study. These antibodies are also called anti-CCP.
The other type of antibody, RF or Rheumatoid factor, is present in some other autoimmune or inflammatory diseases besides RD especially lupus and Sjogren’s syndrome. This autoantibody got its name since it was the first factor found to be commonly produced by people with RD, not because it is the most crucial antibody to detect. RF is an antibody that binds to the Fc portion (antibodies have the shape of the letter Y and the stick part of the Y is the Fc portion) of other antibodies contributing to the formation of what are called immune complexes. RF is found in approximately 80% of people with RD.
What about seronegative RD / RA?
What about the people with RD / RA that are considered seronegative? Lack of positive tests for RF or for ACPAs does not mean that autoantibodies don’t exist. It merely means that the autoantibodies that are present haven’t been discovered or that the levels are below limit of detection in a particular lab. Furthermore, existence of “seronegative” patients is important evidence for the heterogeneity of autoimmune diseases. People who are “seronegative” may have disease that is driven by immune cells other than B cells. Remember, every immune system is fully unique.
Other markers used in RD / RA
Other markers that are often measured in RD are CRP (C-reactive protein) or ESR (Erythrocyte sedimentation rate) as well as 14-33-eta. CRP and ESR are markers of inflammation that are useful for looking at overall health and levels of systemic inflammation. Finally, a marker that is relatively new is referred to 14-3-3-eta. 14-3-3-eta is typically an intracellular protein, however in people with RD, it is often found outside of cells especially in joint synovium. This marker has been found to correlate with radiographic damage and to be identifiable in patients without a high CRP—a good quality in a marker since CRP levels are variable from person to person.
About Kathryne Marks
Kathryne is a PhD candidate in Microbiology and Immunology at Rosalind Franklin University of Medicine and Science studying the molecular regulation of pathogenicity of Th17 cells in the context of autoimmune disease.
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