Aristine Cheng, Infectious Diseases, Internal Medicine
Infectious diseases specialists often treat patients suffering from rare and severe infections—caused not by typical germs, but by opportunistic organisms such as nontuberculous mycobacteria, invasive fungi, and intracellular bacteria. These unusual cases often point to hidden immune defects. Recently, it was discovered that in some patients, the crack in our immune defense is neither due to genetics or human immunodeficiency virus (HIV) infection, but due to autoantibodies that attack the body’s own immune signals, known as cytokines.
In a groundbreaking study published in The New England Journal of Medicine, Dr. Aristine Cheng and colleagues identified autoantibodies against interleukin-23 (IL-23) as a previously unrecognized cause of immunodeficiency in humans. These antibodies block the cytokine IL-23’s function, leaving patients vulnerable to infections that most people easily resist.
This discovery solved a long-standing mystery. Doctors had observed antibodies against another molecule, IL-12, in some patients with thymoma, but not all developed infections. Dr. Cheng’s team found that nearly half of these patients also carried anti–IL-23 antibodies—and the severity of infection correlated strongly with IL-23, not IL-12, neutralization. This is because IL-12 and IL-23 shared an identical subunit.
The findings challenge existing immunological models based largely on animal studies. In mice, IL-23 is mainly linked to autoimmune and anti-fungal responses. In humans, however, Dr. Cheng’s research revealed that IL-23 is also crucial for interferon-γ–driven immunity, activating specialized T cells that fight intracellular pathogens such as mycobacteria. This redefines IL-23 as a key bridge between innate and adaptive immunity.
Clinically, the implications are far-reaching. Patients treated with IL-23–blocking drugs for psoriasis or inflammatory bowel disease may also develop opportunistic infections. More broadly, Dr. Cheng’s work highlights a new form of acquired immunodeficiency, where the immune system sabotages itself—requiring targeted immunotherapy rather than antibiotics alone. As Dr. Cheng notes, “Understanding how immunity fails—whether through genes, microbes, or autoimmunity—is key to protecting patients and improving global health.”
Award to pandemic heroes: because even teddy bears know fearless doctors wear masks and deserve hugs.
Dr. Cheng was awarded Common Health Magazine’s “Doctor of the Year” in 2025.
Experiments to qualify and quantify antibodies in human blood samples are performed in-house using a variety of innovative techniques based on ELISA, flow cytometry, and cell expression assays.