However, this does not necessarily mean LINE-1 cause SLE. Instead, it may be targeted by the immune response as, what the researchers call, “an innocent bystander.”
“The physical interaction of p40 with well-known SLE autoantigens would be compatible with such a role, at least if one assumes that Ro and La are the intended antigens for the immune response,” the researchers write.
The researchers hypothesize that LINE-1 may be a key trigger of the disease, working along with Ro60, La and other RNA binding proteins, according to study co-author Tomas Mustelin, MD, PhD, professor of medicine, Herndon and Esther Maury Endowed Professor in Rheumatoid Arthritis, Division of Rheumatology, Department of Medicine, University of Washington, Seattle.
Depending on future research results, LINE-1 p40 autoantibodies could become part of the lab tests used to assess SLE patients or could be a biomarker in clinical trials of new targeted lupus therapies, Dr. Mustelin says.
The study authors are encouraged by the potential therapeutic implications of their hypothesis, with Dr. Mustelin adding that some of the reverse ranscriptase inhibitors used to treat HIV, which also block the reverse transcriptase activity of LINE-1 p145, would likely stop type I interferon production, potentially tempering SLE disease.
“Our goal is to directly test this possibility,” he says.
Other research must first take place, and one study the authors have underway is analyzing LINE-1 p40 autoantibodies in pediatric lupus patients and in those with other autoimmune diseases that share a type I interferon signature with SLE.
Chandra Mohan, MD, PhD, professor of biomedical engineering and medicine, Cullen College of Engineering, University of Houston, and a Lupus Foundation of America Medical-Scientific Advisory Council member, found the study results promising. “Although there has been accumulating evidence describing the importance of LINE-1 in SLE, this report brings a novel perspective to this field, with a focus on autoantibodies targeting LINE-1 elements,” Dr. Mohan says.
Future studies with independent patient cohorts are needed to validate the researchers’ observations, including a comparison of current diagnostic tests, with careful assessment of sensitivity and specificity, Dr. Mohan notes. Another approach would be longitudinal studies to examine whether the autoantibodies are definite early harbingers of SLE or disease flare.
Mary K. Crow, MD, chair, Department of Medicine, Benjamin M. Rosen Chair in Immunology and Inflammation Research, Hospital for Special Surgery, and chief, Division of Rheumatology, Joseph P. Routh Professor of Rheumatic Diseases in Medicine, Weill Cornell Medical College, New York, has previously reported on the connection between LINE-1 and the pathogenesis of SLE.2,3 Some of her previous work supports the potential role for LINE-1 in some patients with SLE and a link between LINE-1 and type 1 interferon production. However, she believes the connection is still speculative. In a letter to the editor regarding this study, she noted that LINE-1 p40 and other proteins implicated as autoantigens in systemic autoimmune disease should be priority research targets.4
