Drug-induced autoimmunity is not as complex a disease as lupus or ANCA vasculitis because there is a known trigger that can be turned on or turned off. “The rationale underlying this work is that we can learn and study drug-induced autoimmunity, which is a simpler condition, and then apply what we learn to the more complex [conditions],” Dr. Grayson says.
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One potential outcome of research into NET formation and its relationship with lupus and ANCA vasculitis and autoimmunity is that future drug development could focus on blocking NET formation as a new therapeutic target for this family of diseases. Although it is disconcerting to think of targeting neutrophils therapeutically because they fight infection, “we may eventually be able to target a specific process within neutrophils that is causing disease, and then we could be a little more selective in treatment,” Dr. Grayson says.
Medications commonly used in rheumatologic diseases often target lymphocytes and the adaptive immune system. Targeting neutrophils and the innate immune system may more directly target causal factors in certain diseases, he explains.
The evidence right now is “a bit circumstantial until we can put these into animal models and can start blocking these processes in humans. However, there is a mounting body of evidence beyond just this paper suggesting that we are on the right track,” Dr. Grayson says.
Kathy Holliman, MEd, has been a medical writer and editor since 1997.
- Irizarry-Caro JA, Carmona-Rivera C, Schwartz DM, et al. Drugs implicated in systemic autoimmunity modulate neutrophil extracellular trap formation. Arthritis Rheumatol. 2018 Mar;70(3):468–474.
- Nakazawa D, Tomaru U, Suzuki A, et al. Abnormal conformation and impaired degradation of propylthiouracil-induced neutrophil extracellular traps: Implications of disordered neutrophil extracellular traps in a rat model of myeloperoxidase antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis Rheum. 2012 Nov;64(11):3779–3787.
- Carmona-Rivera C, Purmalek MM, Moore E. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity. JCI Insight. 2017 Feb 9;2(3):e89780.
- Sawalha AH. Editorial: The innate and adaptive immune response are both involved in drug-induced autoimmunity. Arthritis Rheumatol. 2018 Mar;70(3):330–333.