Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, but scientists are now uncovering the specific immune mechanisms behind these attacks and how some patients achieve long-term remission. Two emerging areas of research are reshaping how doctors understand and treat conditions like celiac disease and systemic lupus erythematosus (SLE), offering hope for millions of people living with these chronic conditions.

What Exactly Happens When the Immune System Attacks Gluten?

Celiac disease affects roughly 1 in 100 people worldwide, yet around 80% of those people don't know they have it. The condition is far more than a simple food sensitivity. In celiac disease, the immune system mistakes gluten, a protein found in wheat, barley, and rye, for a serious threat and launches a full-scale attack. The problem isn't just that it targets gluten; it's that in doing so, it damages the body's own tissues, particularly the lining of the small intestine where food is digested and nutrients are absorbed.

When gluten is present, immune cells become activated and stimulate the production of specific autoantibodies, such as antibodies that target tissue transglutaminase, an enzyme that modifies proteins including gluten. Together, these immune responses fuel chronic inflammation and tissue destruction in the gut and can affect other parts of the body. Over time, this attack destroys the tiny, finger-like projections called villi that enable nutrient absorption, leading to intestinal injury and malabsorption.

The visible result is intestinal damage, but the deeper issue is the immune misfire driving it. For many people, the most noticeable symptoms occur outside the digestive system entirely, making diagnosis difficult and delayed. The average time from symptom onset to diagnosis has historically stretched across years, sometimes more than a decade.

Why Does Celiac Disease Develop in Some People and Not Others?

Like most autoimmune conditions, celiac disease develops from a combination of factors working together. Understanding these factors helps explain why some people develop the disease while others with similar genetics or exposures do not.

• Genetic Susceptibility: Almost everyone with celiac disease carries a specific genetic variant that affects how their immune system identifies threats. These variants, known as HLA-DQ2 and HLA-DQ8, influence how the immune system reads and responds to proteins like gluten. In people who carry them, fragments of gluten are more likely to be displayed to immune cells in a way that triggers an attack.
• Environmental Triggers: Gluten exposure is necessary but not sufficient on its own. Certain infections, particularly gastrointestinal infections early in life, changes in the gut microbiome, or events that disrupt intestinal barrier function may help trigger the disease in genetically susceptible people, setting the stage for the immune system to overreact when gluten is encountered.
• Developmental and Physiological Factors: Celiac disease can appear at any age, but often emerges during periods of immune or physiological change, such as early childhood, puberty, pregnancy, or after major illness or stress. These shifts may influence immune regulation, tipping a balanced system into autoimmunity in people already at risk.

One reason celiac disease goes undiagnosed so often is that its symptoms are easy to explain away and don't always look like a classic gut problem. Fatigue might be attributed to stress, iron deficiency to diet, bloating to food intolerance, and brain fog to lack of sleep.

How Can Lupus Go Into Remission?

While celiac disease involves a clear dietary trigger, lupus presents a different puzzle. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks the body's own tissues, causing inflammation that can affect the skin, joints, kidneys, lungs, brain, blood vessels, and heart. It affects approximately 3.4 million people worldwide, most commonly women and disproportionately people of African ancestry.

Lupus is marked by an unpredictable cycle of flares and remissions, in which symptoms can worsen, ease, or disappear entirely. This volatility can make the disease deeply isolating, as its daily realities are often invisible and difficult for others to understand. In rare cases, these periods of remission can last years, and even decades.

One such case is Hazel Harris, who was diagnosed with SLE in 1986 at age 33. She experienced the classic butterfly rash on her face, puffy eyes, deep fatigue, and severe leg swelling. After four or five years of lupus, she went into spontaneous remission 25 years ago without medication. Today, she has been in clinical remission for more than 20 years, dancing and practicing tai chi without the daily constraints that once defined her life.

"It was very gradual. I didn't have a 'Thank you Jesus, I'm healed' moment. I just started thinking, maybe I'm healing. Maybe," Harris explained.

Hazel Harris, patient with SLE in remission

Harris's experience places her among a small and poorly understood group of people with SLE who enter sustained, drug-free clinical remission. While modern therapies can reduce disease activity, true long-term remission without immunosuppression remains rare and largely unexplained.

What Is a $15 Million Study Revealing About Lupus Remission?

A large international research effort funded by the National Institutes of Health (NIH) is now examining patients in long-term, medication-free remission to determine whether the disease has genuinely resolved or entered a distinct biological state. The project spans multiple continents and brings together immunology, neurology, microbiome research, and advanced data science.

One of the study's leaders is Betty Diamond, an immunologist at the Feinstein Institutes who has spent decades studying autoimmune disease. For decades, lupus research has focused on flares, how to suppress them, shorten them, and limit the organ damage they cause. Remission, when it occurred, was treated as an endpoint rather than a subject of study. That is now changing.

"While there have been a few successes in lupus clinical trials, there have also been many failures. It seemed to my colleagues and me that perhaps we were thinking about how to achieve success the wrong way," Diamond stated.

Betty Diamond, immunologist at the Feinstein Institutes for Medical Research

Active SLE is highly heterogeneous, making it difficult to study and, in turn, difficult to treat. Studying remission, Diamond and her colleagues believe, may point to a more meaningful therapeutic goal. Rather than focusing solely on suppressing active disease, researchers can ask what kind of immune balance patients in long-term remission have achieved and whether that state can be induced or sustained.

The team reasoned that among people in remission, roughly 5% relapse each year. Over five years, that could mean about a quarter of participants experiencing relapse. By examining patients just before and at the earliest stages of relapse, the researchers hope to capture meaningful biological differences that may be obscured once the disease is fully active and multiple immune pathways are simultaneously engaged.

So far, the team has examined approximately 120 people in remission, 20 healthy individuals, and 20 patients with active disease. Using single-cell sequencing and other high-resolution techniques, the researchers are mapping the immune system at an unprecedented level of detail, examining the activity, identity, and molecular state of individual immune cells in patients in remission, with active disease, and in healthy controls.

"What we already know is that it's clear that people in remission don't look like healthy individuals. The team is already observing immune system changes that, if confirmed in larger cohorts, could point to new therapeutic targets," Diamond noted.

Betty Diamond, immunologist at the Feinstein Institutes for Medical Research

How Are Immunotherapies Expanding Beyond Cancer Treatment?

While much of the recent excitement around immunotherapy has centered on cancer treatment, researchers are now testing whether these same immune-harnessing approaches can help patients with autoimmune diseases, infections, allergies, and brain conditions. Clinical trials of immunotherapies have rocketed in the past decade as researchers have turned their understanding of the body's defenses into powerful new treatments. A global registry of clinical trials listed 1,257 trials of immunotherapies between 2006 and 2016. The figure leapt to 4,591 in the past decade.

Cancer immunotherapies tend to ramp up immune attacks; immunotherapies for other conditions aim to dampen them down. Some of the most exciting new immunotherapies draw on last year's Nobel Prize-winning work on regulatory T cells, or Tregs. Humans have dozens of different immune cells that attack invading pathogens, but Tregs are unusual: they stand the immune system down once the threat has been dealt with.

Therapies are in the pipeline for dementia and autoimmune diseases from type 1 diabetes and rheumatoid arthritis to lupus and chronic inflammation. One therapy under development uses Tregs to treat inflammatory bowel disease, a condition that affects at least 7 million people globally.

"Probably half of all deaths have a component that is immunological. It is an underlying theme across ageing, autoimmune diseases, allergies, infectious diseases, inflammatory diseases like diabetes. But one of the great things about the immune system is that it is very easy to change. We can adapt it to our purposes," said Adrian Liston, an immunologist and professor of pathology at the University of Cambridge.

Adrian Liston, immunologist and professor of pathology at the University of Cambridge

Steps to Understanding Your Autoimmune Condition

• Seek Early Diagnosis: If you experience unexplained fatigue, rashes, joint pain, or digestive issues that persist for weeks, ask your doctor about autoimmune screening. Early diagnosis prevents irreversible organ damage and allows for timely treatment.
• Understand Your Specific Condition: Autoimmune diseases vary widely in symptoms and triggers. Learning whether your condition involves a dietary trigger (like celiac), environmental factors, or genetic predisposition helps you manage it more effectively.
• Track Symptom Patterns: Keep a record of when symptoms worsen or improve, what you ate, stress levels, and infections. This information helps your doctor identify your personal triggers and adjust treatment accordingly.
• Connect With Support Communities: Joining patient support groups or online communities helps counter the isolation these conditions often create and provides practical advice from others living with the same diagnosis.

The convergence of research into celiac disease, lupus remission, and new immunotherapies signals a fundamental shift in how medicine approaches autoimmune conditions. Rather than viewing these diseases as permanent battles to suppress, researchers are now asking deeper questions about immune balance, remission, and whether the immune system can be retrained to achieve lasting health.