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When the Immune System Gets It Wrong: Why Autoimmune Diseases Affect Women So Disproportionately 

Emma Sosa

The immune system is designed to protect us. It identifies viruses, bacteria, and other threats and marshals in an army of cells and other substances in the fight. But what happens when that army can no longer identify friends from foe and turn the body against itself? 

That's a central question of autoimmunity and autoimmune diseases. 

Today, more than 80 different types are known, including lupus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. In all, they affect millions of people, predominantly women -- in fact, nearly 4 out of every 5 people living with an autoimmune condition are women, and studies suggest at least 10 percent of the population has an autoimmune disease of some kind.  

It’s not just: why do women have autoimmune disease? 

It's: why does our defense system sometimes stop protecting the body, and start turning against it?  

A Defense System that Misfires 

Our immune system is a highly complex entity comprised of cells, organs, proteins, signaling chemicals, all working together. In fact, one very important part of this work is to differentiate self from non-self -- recognizing all the parts of ourselves as "friendly" rather than as "invader". When autoimmune diseases manifest, this self/non-self-recognition can be thrown out of sync. 

Instead of protecting "self" while attacking "foreign intruders" - or invaders such as viruses and bacteria -- some part of the immune system, the cells or an army of antibodies, mistakenly recognize a part of our healthy bodies -- say, a joint, a skin surface or internal organ system such as the thyroid -- and the pancreas to, say, help regulate metabolism, and attack it. What a person's body attacks depends on the autoimmune disease, a person's genes, the individual and a complex web of other influences. But one factor is becoming increasingly evident: The answer to this perplexing problem involves interactions of genetics, environment, hormones, the microbiome and how the immune system itself is regulated. 

 Why Are Women More Affected? 

One of the most compelling areas of autoimmune disease research is why sex differences appear to be so pronounced. In women, an autoimmune attack is roughly three to 12 times more likely than it is for men. The answer is complex and likely multi-faceted, but two prominent avenues of investigation explore what might be unique about women. 

Genetics and the X chromosome: Women possess two X chromosomes, while men generally carry one. Several crucial immune-regulatory genes are on the X chromosome. Researchers speculate that differences in how X chromosomes operate may account for significant differences in the female immune response. 

Hormones: Hormones, particularly estrogen, play a role in regulating not just female sexual development and function but immune system operations as well. High levels of estrogen, for instance, can both enhance the effectiveness of the female immune response and increase propensity toward immune dysfunction. An overly active immune system could potentially be both a helpful defense against an infection and, unfortunately, a recipe for autoimmune disorder.  

Thus, the exact same characteristic – that enables women to put up the robust defense against infection – might also make them uniquely susceptible to autoimmune conditions.  

Research continues to unravel how these diverse genetic and hormone effects mesh. 

Environmental and Lifestyle Factors Matter Too 

Genes aren't the whole story; recent studies are bringing an array of environmental factors into the spotlight in autoimmunity as well, from infections to stress to the compounds we ingest or inhale. This has also prompted investigations into the trillions of microscopic life forms within the digestive tract known collectively as the gut microbiome, which researchers say interact daily with the immune system. Changes in the bacterial mix found in our guts, for example, could potentially influence inflammatory responses and the capacity of our defenses to distinguish between our bodies and potential foreign threats. These discoveries do not pinpoint a specific food or even a specific bacteria as responsible -- that's likely to be a part of a far larger whole -- but show environmental effects and their relationships to immunity are complex. 

An Autoimmune Life extends Beyond the Lab 

The impact of autoimmune conditions extends beyond lab values and diagnostic imaging; the symptoms, ranging from fatigue and muscle weakness to painful joints, chronic pain, inflammatory responses and cognitive impairment, affect virtually every aspect of an individual's life. Physical activity, for example, a key recommendation in managing health, presents a fascinating challenge: for some with an autoimmune disease, properly monitored exercise and physical rehabilitation can be incredibly beneficial -- building muscle strength, improving cardiovascular function, and managing energy levels. However, symptoms vary considerably, and exercise that may feel manageable on any given day could feel nearly impossible if disease activity escalates during another. Thus, there is increasing emphasis on the need for personalized recommendations that account for varying levels of disease activity. 

The Hispanic Health Perspective 

While no single ethnic group is immune to autoimmune diseases, research is examining variations and considerations within particular communities. For the Hispanic population, investigators are looking at how complex interrelationships between factors such as genetic heritage, social-economic and cultural influences and access to health care might play unique roles in influencing the prevalence and trajectory of different forms of autoimmune disease. Understanding of specific types of autoimmune disease in certain Hispanic communities – for example, that lupus can be notably more severe and manifest in different ways among these populations, as one important body of research suggests - reinforces the need for health-focused medical research for all people. As medical researchers say, one size doesn't fit all; just as no two individuals who carry the autoimmune "diagnosis" present the same symptoms, neither should medical research reflect the disease solely from one population's point of view. 

What will autoimmune disease research do in the future? 

Perhaps the greatest sea change in the study of autoimmunity is moving away from studying it as isolated diseases. Instead, scientists are beginning to investigate the condition from an integrative perspective – where immune system function, hormones, genetics, the environment, metabolism, the microbiome and our own physiology all intersect as part of this larger pattern in autoimmunity. Through these avenues of investigation, research has the potential not only to improve detection and management for already-diagnosed autoimmunity patients, but also to predict risk before critical damage occurs to a patient’s vital organ and systems - and eventually to offer truly individualized therapies targeted to interrupt the specific pathway that leads toward autoimmune disease, rather than broadly suppress the immune system.  

In the end, the hope of autoimmune disease researchers worldwide is to truly comprehend the cause of immunity’s broken defense system so we can ultimately learn how to protect it, and the people it protects.  

This knowledge may turn out to be one of the most significant medical breakthroughs in years because, as it has become alarmingly clear, for the body to flourish, sometimes what is most dangerous isn't the force that crashes in from outside - but rather a system that can no longer recognize that it should be protecting us against itself.