Researchers from Johns Hopkins report that in the most severe cases of rheumatoid arthritis (RA), enzyme-activating antibodies may serve as a marker for the disease. In the study, researchers note that the presence of “so-called” PAD3/PAD4 cross-reactive autoantibodies could serve as the basis for the first antibody-specific diagnostic test designed to distinguish those with severe RA from patients with less aggressive forms of the disease. Researchers say antibodies were present in 18% of 44 fluid samples from one research collection and in 12% of another collection of 194 in patients with severe cases of RA. The study indicates that further examination of patients’ medical records revealed 80% of patients with the antibody saw their disease worsen over the previous year, while only 53% without the antibody exhibited disease progression.
The results go on to suggest that when researchers compared average scores of disease-damaged joints, they observed that patients with the antibody exhibited an average deterioration in joints and bones by a score of 49. Patients without the antibody reportedly had an average degradation in their score of 7.5, indicating much milder disease. The team also notes that they pinpointed how the PAD3/PAD4 cross-reactive auto-antibodies may contribute to more severe, erosive disease in RA.
To determine this, a series of experiments were performed to gauge the antibodies’ effects on PAD4 in response to varying cell levels of calcium, on which PAD enzymes depend. According to the team, the results showed that the antibodies greatly increase PAD4 enzyme function at the low levels of calcium normally present in human cells. The results also suggested that PAD4 activity was 500 times great in the presence of antibodies than when they were absent.
The researchers add that tests of the antibody and enzymes’ chemical structures later showed that the antibodies bind to PAD4 in the same region as calcium, indicating that the antibodies may be substituting for calcium in activating the enzyme. Erika Darrah, PhD, biologist, lead study investigator, states that next the team plans to implement long-term monitoring of arthritis patients in order to determine when the antibody first appears in the blood, and when intervention may have maximum impact in preventing or stalling disease progression.
[Source: Johns Hopkins Medicine]