Having an autoimmune disease does not automatically make you immunocompromised, but it can move you closer to that category depending on your specific condition, the medications you take, and how your disease affects your body over time. The two terms describe opposite problems: autoimmune disease means your immune system is overactive and attacking your own tissues, while being immunocompromised means your immune system is too weak to fight off infections effectively. The confusion is understandable, though, because the treatments used to calm an overactive immune system often work by suppressing it, and some autoimmune diseases can independently weaken parts of your immune defense.
Why They’re Not the Same Thing
Your immune system is designed to tell the difference between your own cells and foreign invaders like bacteria, viruses, and parasites. In autoimmune disease, that distinction breaks down. One well-studied way this happens is through molecular mimicry: a pathogen’s proteins look so similar to your body’s own proteins that immune cells trained to fight the infection start attacking healthy tissue instead. The result is an immune system that’s working too hard, not too little.
Immunodeficiency is the opposite problem. If you have an immunodeficiency, your immune system can’t mount a strong enough response to threats. You get sick more often, infections last longer, and they’re harder to treat. Someone can be born with an immunodeficiency (a primary condition) or develop one later due to illness, medication, or other factors (a secondary condition).
So at the biological level, autoimmune disease and immunodeficiency are distinct. But modern research increasingly treats them as related rather than separate. Autoimmunity and immunodeficiency are now regarded by immunologists as “two sides of the same coin,” because the same underlying immune system dysfunction can produce both problems simultaneously.
How Medications Change the Picture
The most common reason someone with an autoimmune disease becomes immunocompromised is their treatment. To stop your immune system from attacking healthy tissue, many medications work by turning down immune activity broadly, which also reduces your ability to fight real infections.
Corticosteroids like prednisone are among the most widely prescribed. At higher doses, taken over longer periods, they clearly suppress immune function. The threshold used in clinical settings to classify someone as immunocompromised from steroids is roughly 0.5 mg per kilogram of body weight per day (of prednisone or its equivalent) taken for more than three months. For someone weighing 150 pounds, that’s about 34 mg daily. Lower doses or shorter courses have a milder effect, though they can still reduce your immune response to some degree.
Beyond steroids, several other categories of drugs used for autoimmune conditions suppress immune function. Disease-modifying antirheumatic drugs (DMARDs), drugs that block cell division in immune cells, and calcineurin inhibitors all work by interfering with different parts of the immune response. Biologic therapies, which are engineered antibodies that target specific immune cells, can have an especially focused suppressive effect. One biologic in particular, rituximab, depletes a type of white blood cell called B cells, which are responsible for producing antibodies. This has a measurable impact on your ability to respond to vaccines and fight certain infections.
The Vaccine Response Problem
One of the most practical ways to measure whether someone is immunocompromised is to look at how well they respond to vaccines. If your immune system can’t build a strong antibody response after vaccination, you’re functionally less protected than someone with a healthy immune system.
Rituximab provides a clear example. In a study of people with rare autoimmune rheumatic diseases who received four doses of a COVID-19 vaccine, the timing of their last rituximab treatment strongly predicted whether they developed adequate antibodies. Among those who had never received rituximab, 100% responded to the booster. For those whose last rituximab dose was more than 12 months earlier, 80% responded. That dropped to about 55% for those treated 6 to 12 months prior, and just 43% for those who had received rituximab within the last 6 months.
Interestingly, standard oral immunosuppressants did not significantly affect the vaccine response in the same study. This highlights that not all autoimmune medications suppress your immunity equally. The type of drug, the dose, and the timing all matter.
When the Disease Itself Weakens Immunity
Medications aren’t the only factor. Some autoimmune diseases can directly compromise parts of your immune defense, independent of treatment.
Lupus is a well-studied example. The disease is closely linked to deficiencies in the complement system, a group of proteins that form part of your innate immune defense and help clear dead cells and immune complexes from the body. When these proteins don’t work properly, you’re more vulnerable to certain infections, particularly from bacteria with protective outer coatings (encapsulated organisms). About 90% of people with a deficiency in one specific complement protein, C1q, develop lupus, illustrating how tightly autoimmunity and immune vulnerability are connected at the genetic level.
Lupus can also cause functional hyposplenism, a condition where the spleen stops working properly even though it’s still physically present. The spleen plays a key role in producing and maturing immune cells that fight bacterial infections. About 7% of people with lupus have some degree of spleen dysfunction, which leaves them more susceptible to serious bacterial infections. Other autoimmune conditions linked to hyposplenism include inflammatory bowel disease and celiac disease, where the prevalence is considerably higher (33% to 76% for celiac disease).
The underlying mechanism in many of these cases involves problems with apoptosis, the body’s process for cleaning up old or damaged cells. When cells aren’t properly cleared, their internal components get exposed to the immune system, triggering the production of antibodies against the body’s own proteins. This same failure of cellular cleanup can leave gaps in immune defense that pathogens exploit.
What This Means in Practice
Whether you’re considered immunocompromised depends on a combination of factors specific to your situation. Someone with mild, well-controlled rheumatoid arthritis managed with a low-dose DMARD is in a very different position than someone with active lupus on high-dose steroids and rituximab. There’s no single answer that applies to everyone with an autoimmune diagnosis.
A few things are worth knowing. If you take any medication that suppresses immune function, you may need additional vaccine doses or different timing around your infusions to get adequate protection. If you take rituximab, scheduling vaccinations at least two weeks before your next infusion (when possible) can improve your antibody response. Your susceptibility to infections may fluctuate as your treatment changes, so the question of whether you’re immunocompromised isn’t fixed. It can shift over time.
The bottom line: an autoimmune disease diagnosis alone does not make you immunocompromised, but the treatments you receive and the specific ways your disease affects your body can. Many people with autoimmune conditions live with some degree of immune suppression, ranging from barely noticeable to clinically significant, depending on where they are in their treatment.