There are two known types of rheumatoid arthritis today: seropositive rheumatoid arthritis and seronegative rheumatoid arthritis.
Seropositive RA Versus Seronegative RA
A seropositive rheumatoid arthritis diagnosis means that your blood tests show the presence of anti-cyclic citrullinated peptides (anti-CCPs), also known as anti-citrullinated protein antibodies (ACPAs).1
Anti-CCPs are antibodies produced against the body’s proteins, which undergo a molecular change in structure called citrullination.
A positive result on the presence of these antibodies, coupled with symptoms usually associated with RA, can mean a possible RA diagnosis. These antibodies are present in 60 to 80 percent of people battling RA, and studies have shown that these develop ahead of the clinical symptoms by 5 to 10 years.
How Are These Types of Arthritis Diagnosed?
Seropositive RA can be diagnosed by the presence of the rheumatoid factor (RF). A rheumatoid factor is another antibody that’s detected by various tests, and is directed to sites on other antibodies.
RFs also occur in patients with several other conditions not just limited to RA, and patients who have anti-CCP antibodies are also positive for RFs.
Meanwhile, seronegative rheumatoid arthritis is the exact opposite — the tests don’t show the presence of the antibodies previously mentioned in your blood.
Dr. David Pietsky, professor of Medicine and Immunology at the Duke University School of Medicine mentions that, “You can have RA without being seropositive, but it is easier to meet the criteria if you are positive.” 2
One difference between seropositive RA and seronegative RA patients is the presence of a common sequence of amino acids called the human leukocyte antigen (HLA) genetic site or locus. This sequence creates the proteins that control immune responses.
Other differences between seropositive and seronegative rheumatoid arthritis are yet to be determined, but one clue lies in your genetic makeup leading to differences like extra-articular manifestations, which include lung or eye involvement or rheumatoid nodules.
Dr. John Carter, associate professor and chief of the Division of Rheumatology and director of Clinical Research at the University of South Florida explains, “Depending on the trigger and the individual’s genetic makeup you get different manifestations of what we call RA, and these different presentations are lumped into one diagnosis.”3
What Causes These Types of Rheumatoid Arthritis?
While there are no definite causes that state the connection between these amino acids and RA itself, one theory says that the amino acids attach to protein parts called citrullinated peptides, which then contribute to anti-CCP antibody production.
A person who has seronegative RA is also unlikely to have seropositive RA, but there’s a possibility for the seronegative patient to be a diagnosed with a different disease altogether. Pietsky gives three examples:
Psoriatic arthritis: this can be diagnosed if someone with seronegative rheumatoid arthritis develops a skin rash
Chronic gout: based on joint fluid tests in what appears to be RA
Osteoarthritis: can sometimes be confused with RA
Contrary to popular belief, just because seronegative RA tests show that the body does not have antibodies, it does not make the disease less mild.4