“Disease of 1,000 Faces”: How Researchers Are Unraveling Autoimmunity and Changing Care

Ruth Wilson’s long road to diagnosis

For six years doctors repeatedly misdiagnosed or dismissed Ruth Wilson’s rashes, swelling, fevers and intense pain. Only after begging for one more test during an emergency visit did she learn her kidneys were failing — the result of her immune system attacking her own body. The diagnosis: lupus, often called the “disease of 1,000 faces” for the wide variety of symptoms it can cause.

“I just wish there was a better way that patients could get that diagnosis without having to go through all of the pain and all of, like, the dismissiveness and the gaslighting,” Wilson said.

Why this matters

Autoimmune conditions — a broad and growing group of diseases — affect as many as 50 million Americans and millions more worldwide. The National Institutes of Health recently catalogued about 140 autoimmune disorders. Together, they are a leading but often invisible cause of chronic illness, ranging from Type 1 diabetes and rheumatoid arthritis to multiple sclerosis and Sjögren’s disease.

From treating symptoms to targeting causes

Scientists are now leveraging advances from cancer biology and lessons from the COVID-19 pandemic to decode the biology behind autoimmunity. Rather than only easing symptoms, researchers hope to interrupt the immune processes that trigger disease. Early efforts are promising:

• CAR-T therapy: Trials repurposing patients’ own engineered immune cells to eliminate the rogue immune cells that drive disease have produced encouraging results. The first lupus patient treated with CAR-T in Germany (March 2021) reportedly remains in drug-free remission.
• Early intervention: Teplizumab, a drug shown to delay onset of Type 1 diabetes symptoms, offers a model for catching disease in a treatable window. The NIH’s proposed five-year plan for autoimmune research urges pursuing similar early-intervention strategies.

How autoimmunity starts

The immune system relies on overlapping mechanisms to distinguish self from invader, training cells such as T cells and B cells to tolerate the body’s own tissues. When that balance breaks down — through genetic predisposition, infections, drugs, pollutants, smoking or other environmental "hits" — the immune system can turn on the body.

Genetics matter but are not everything. Identical-twin studies show that non-genetic triggers are crucial. Women are disproportionately affected: estrogen and differences related to the X chromosome likely contribute, and around 90% of lupus cases occur in women.

Neutrophils, NETs and cardiovascular risk

Researchers like Dr. Mariana Kaplan and colleagues at the NIH are exploring early cellular events that may initiate autoimmunity. One suspect: neutrophils, the most common white blood cell. Certain neutrophils release webs of DNA and proteins called neutrophil extracellular traps (NETs) to trap microbes. In lupus and related conditions, abnormal NET formation or defective clearance may leave debris that other immune cells mistake for foreign, sparking inflammation.

Kaplan’s team also links NETs to premature cardiovascular disease in autoimmune patients: NET-driven damage to blood vessels may accelerate atherosclerosis, increasing heart attack and stroke risk at younger ages.

Heterogeneity — the case for subtyping diseases

Wide variation in symptoms and treatment responses suggests diseases like lupus are not single entities but collections of related conditions with shared features. In rheumatoid arthritis, tissue-level profiling identified multiple inflammatory subtypes, a finding that is reshaping therapeutic strategies and could guide personalized treatment choices in other autoimmune illnesses.

Life with lupus — beyond lab tests

Wilson’s life today includes daily pain, deep fatigue and episodic brain fog even after treatments that preserved her kidneys. She takes a monthly targeted infusion and several daily medications to control inflammation and symptoms. Flares — sudden, severe symptom spikes — can last days and disrupt work and family life.

She now volunteers to educate patients, the public and clinicians about lived experience. Wilson emphasizes that clinical trials should measure outcomes that matter to patients, such as improvements in cognition, energy and daily function, not only laboratory markers of inflammation.

Big studies and patient-driven research

Large initiatives like the Lupus Landmark Study, which will follow 3,500 patients and collect biological samples, aim to map disease variation and identify markers of flares, progression and treatment response. Combined with patient advocacy, these efforts push research to align more closely with patients’ real-world needs.

Looking ahead

While many challenges remain, advances in immunology, cellular engineering and precision profiling are creating new opportunities to prevent, arrest or even reverse some autoimmune diseases. For patients like Wilson, that hope is transformative — and researchers say this may be the most promising moment yet in autoimmune research.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation. The AP is solely responsible for all content.