Findings in context
“The authors did a number of steps laudably,” James T. Rosenbaum, MD, chair of the division of arthritis and rheumatic diseases and the Edward E. Rosenbaum Professor of Inflammation Research at Oregon Health & Science University, Portland, commented in an interview. Specifically, they used a variety of appropriate controls, had discovery and validation sets, achieved a fairly good sample size, and applied the phage library technique.
Dr. James T. Rosenbaum
“Despite this technological tour de force and the need for a sensitive and specific blood test to diagnose nonradiographic axSpA, this study is preliminary,” he cautioned. “For example, the authors found antibodies to DUX4 in 8% of axSpA patients versus 3% of healthy controls, 4% of patients with chronic low back pain, and 7% with RA. It took a combination of antigens to enhance the diagnostic accuracy of the ASAS criteria to diagnose axSpA. For each antigen that was studied, more than 80% of the axSpA patients had no detectable antibodies.”
Importantly, rheumatic diseases are often immune mediated without being autoimmune, calling into question the role of the antibodies, according to Dr. Rosenbaum.
“Even if further studies validate these observations, additional research needs to be done to support the concept that these antibodies cause disease as opposed to being mere epiphenomena as is suggested by the low prevalence,” he concluded. “Current hypotheses as to the cause of ankylosing spondylitis now point to the microbiome and autoinflammatory rather than autoimmune pathways, but the jury is still out.”
Dr. Somers and three coauthors disclosed having a patent pending on the markers. The study was funded by a personal grant from the Agency for Innovation by Science and Technology Flanders. Dr. Rosenbaum disclosed that he consults for AbbVie, Gilead, Novartis, Pfizer, Roche, and UCB.
SOURCE: Quaden D et al. Arthritis Rheumatol. 2020 Jul 8. doi: 10.1002/art.41427.