Health Conditions / Autoimmune Diseases / Primary Immunodeficiency Diseases

You’ve probably heard a lot about how important your immune system is, especially over the past few years. Phrases like “herd immunity” and “immunocompromised” proliferated in official public health updates, news stories, and health care centers as experts navigated all the uncertainties of the COVID-19 pandemic. Now, we know that the virus can affect anyone, but it can lead to particularly risky complications for the most vulnerable people in our communities.1Of course, the immune system’s job is to protect your body from all invaders that may be harmful, not just certain viruses: When functioning properly, it alerts your body to a wide range of potential threats and helps it respond accordingly. However, some people have dysfunctional immune systems—which are also known as weakened or compromised immune systems—that cause their bodies’ protective response to be under- or overactive, per Johns Hopkins Medicine.There’s no exact figure for how many people live with weakened immune systems, but it’s safe to say it’s in the millions, Leonard Calabrese, DO, a rheumatologic and immunologic disease expert at the Cleveland Clinic, tells SELF. Some research suggests at least 7 million adults in the United States are immunocompromised, per the Centers for Disease Control and Prevention (CDC). Below, experts explain the factors that can break down the immune system’s defenses, the common symptoms associated with compromised immune systems, and what kinds of treatments are available to help.What is a weakened immune system, exactly?Your immune system is an intricate network of cells, tissues, and organs (as well as the substances they make) that, generally speaking, fight disease and infection, according to the National Institutes of Health (NIH). White blood cells may come to mind, but there are lots of body parts that play important roles in your immune health, like your skin, lymph nodes and vessels, thymus gland (which makes white blood vessels), spleen, tonsils, and bone marrow, among others.The immune system is generally broken down into two parts, Scott Weisenberg, MD, an infectious disease specialist at NYU Langone Health, tells SELF. These are called the innate (or inherited) and the adaptive (or acquired) immune systems. The major difference between the two is that you’re born with the former, and your body develops the latter.2 The innate immune system is the first to respond to an invader—such as a harmful germ—by surrounding it with protective cells and, if all goes as planned, killing it. The adaptive immune system supports your innate response by producing proteins called antibodies.2 These are designed to counter a specific threat, like certain viruses or bacteria, should your body be exposed to them and need backup in the future, per Johns Hopkins Medicine.Problems can occur when the immune system either doesn’t respond enough or responds too strongly, Dr. Calabrese says. “A compromised immune system fails to either detect danger or [reacts] aggressively and causes collateral damage to our systems,” he explains.3It’s worth noting that problems with the immune system exist on a spectrum, Dr. Calabrese adds. The potential health risks posed by a weakened immune system aren’t the same if you’re comparing one person who, for example, has moderate allergies, to someone who’d recently had an organ transplant. “They’re hardly in the same category,” Dr. Calabrese says.Back to topWhat causes a weakened immune system?Any number of health issues, such as mild asthma, can affect your body’s ability to fight disease and infection—and certain lifestyle factors, like smoking tobacco and not getting enough sleep, can also interfere with your body’s ability to stay balanced and heal, the CDC says. However, there are several major factors that can compromise your immune system’s defenses. These include:Autoimmune diseasesAutoimmune diseases are characterized by a malfunctioning immune response; essentially, your body goes a bit rogue and starts to attack its healthy cells, tissues, and organs, according to the National Institutes of Health (NIH). There are more than 80 autoimmune diseases that experts know of, including rheumatoid arthritis, type 1 diabetes, lupus, and many more; these conditions are thought to impact at least 24 million people in the United States, while an additional 8 million are estimated to have blood markers that point to their susceptibility of developing one of these disorders, per the NIH.

OverviewChronic granulomatous (gran-u-LOM-uh-tus) disease (CGD) is an inherited disorder that occurs when a type of white blood cell (phagocyte) that usually helps your body fight infections doesn’t work properly. As a result, the phagocytes can’t protect your body from bacterial and fungal infections.People with chronic granulomatous disease may develop infections in their lungs, skin, lymph nodes, liver, stomach and intestines, or other areas. They may also develop clusters of white blood cells in infected areas. Most people are diagnosed with CGD during childhood, but some people may not be diagnosed until adulthood.SymptomsPeople with CGD experience serious bacterial or fungal infection every few years. An infection in the lungs, including pneumonia, is common. People with CGD may develop a serious type of fungal pneumonia after being exposed to dead leaves, mulch, or hay.It’s also common for people with CGD to experience infections of the skin, liver, stomach and intestines, brain, and eyes. Signs and symptoms associated with infections include:FeverChest pain when inhaling or exhalingSwollen and sore lymph glandsA persistent runny noseSkin irritation that may include a rash, swelling, or rednessSwelling and redness in your mouthGastrointestinal problems that may include vomiting, diarrhea, stomach pain, bloody stool, or a painful pocket of pus near the anusWhen to see a doctorIf you think you or your child has a type of fungal pneumonia from being around dead leaves, mulch, or hay, get medical care right away. If you or your child has frequent infections and the signs and symptoms listed above, talk to your doctor.CausesA mutation in one of five genes can cause CGD. People with CGD inherit the gene mutation from a parent. The genes normally produce proteins that form an enzyme that helps your immune system work properly. The enzyme is active in white blood cells (phagocytes) that catch and destroy fungi and bacteria to protect you from infections. The enzyme is also active in immune cells that help your body heal.When there are mutations to one of these genes, the protective proteins are not produced, or they’re produced but they don’t function properly.Some people with CGD don’t have one of these gene mutations. In these cases, doctors don’t know what causes the condition.Risk factorsBoys are more likely to have CGD.DiagnosisTo diagnose CGD, your doctor will review your family and medical history and conduct a physical exam. Your doctor may order several tests to diagnose CGD, including:Neutrophil function tests. Your doctor may conduct a dihydrorhodamine 123 (DHR) test or other tests to see how well a type of white blood cell (neutrophil) in your blood is functioning. Doctors usually use this test to diagnose CGD.Genetic testing. Your doctor may request a genetic test to confirm the presence of a specific genetic mutation that results in chronic granulomatous disease.Prenatal testing. Doctors may conduct prenatal testing to diagnose CGD if one of your children already has been diagnosed with CGD.TreatmentTreatment for CGD is aimed at helping you avoid infections and manage your condition. Treatments may include:Infection management. Your doctor will work to prevent bacterial and fungal infections before they occur. Treatment may include continuous antibiotic therapy, such as trimethoprim and sulfamethoxazole combination (Bactrim, Sulfatrim Pediatric) to protect against bacterial infections and itraconazole (Sporanox, Tolsura) to prevent fungal infections. Additional antibiotics or antifungal medications may be necessary should infection occur.Interferon-gamma. You may have interferon-gamma injections periodically, which may help boost cells in your immune system to fight infections.Stem cell transplantation. In some cases, a stem cell transplant can provide a cure for CGD. Deciding to treat with stem cell transplantation depends on a number of factors, including prognosis, donor availability and personal preference.Potential future treatmentsGene therapy is currently being explored for CGD treatment, but further research is necessary.Researchers are also investigating repairing defective genes to treat CGD.Updated: 2023-03-03Publication Date: 2020-02-18

Other possible symptoms of PIDDs include digestive issues, delayed growth or development, or inflammation of the internal organs, according to the Mayo Clinic.There are several treatments for PIDDs, and narrowing down your exact gene error can sometimes help. Unfortunately, identifying a PIDD can take a while. On average, it takes people more than six years to get an accurate diagnosis, “which can be fatal in some cases,” Dr. Bogunovic says.5 There are lots of reasons a diagnosis can be delayed, he says, including that primary immunodeficiency diseases sometimes don’t appear until later in a person’s life, primary care doctors aren’t always aware of the vast range of PIDDs or their unique symptoms, and it might be difficult for some people to access the right experts (like an immunologist) or credible institutions for both geographic and socioeconomic reasons.The good news is, that’s not always the case. Dr. Peng has been on care teams that provided patients with a diagnosis within a week, thanks to experts working together on several fronts and diving into the person’s genetics and medical history. When it comes to PIDD treatments, there are a few options, and each has potential pros and cons. They fall into the following three broad categories.Symptom and infection management This is often the most accessible avenue, and lots of people diagnosed with PIDDs do well by managing infections for years and years, Dr. Peng says. For example, according to the Mayo Clinic, if you have frequent bacterial infections, longer courses of antibiotics or intravenous antibiotics may be recommended. Long-term antibiotic use may help to ward off an infection before it starts too. If a person is lacking certain antibodies, immunoglobulin therapy—typically an IV treatment—can help replace the lacking proteins. Immune system replacement This can be done via a bone marrow or stem cell transplant.6 For a stem cell transplant, a doctor takes stem cells (a.k.a. blood-forming cells) from a donor with a healthy immune system. The doctor also wipes out the patient’s immune system (essentially erasing the genetic errors in question). Then, healthy stem cells from a donor are put into the blood of the patient. These new stem cells replicate over time, completely replacing the person’s formerly malfunctioning immune system. Unlike with managing symptoms, if all goes well, the patient is cured. Unfortunately, Dr. Peng says, moving forward with a stem cell transplant is not a simple decision for the doctor or the patient. “You’re basically knocking out all of the person’s immune defenses, putting them at incredible risk for infection before you give them back someone else’s stem cells,” she says. Even after the cells have been transferred to the person receiving the transplant, it takes time for what’s essentially a brand-new immune system to reach fighting capacity. Unfortunately, there’s also a risk that the donor’s new cells will view the recipient’s body as a threat and start attacking otherwise healthy tissues, Dr. Peng says. Genetic testing is critically important when screening candidates for a stem cell transplant, she adds, because some genetic errors live elsewhere in the body, not just the stem cells.Gene therapy Unlike a stem cell transplant, in gene therapy, technology is used to extract a patient’s own stem cells, edit the PIDD-related genetic error out of a person’s stem cells, then deliver the corrected stem cells back into their body intravenously, per the Mayo Clinic. Most gene therapy is in its early stages and not ready for patient use yet, Dr. Peng says, but there are several clinical trials that are currently testing these therapies on humans. According to the Immune Deficiency Foundation, there are only a few current use cases for gene therapy outside of these trials, including for children with certain types of SCID. 

OverviewCommon variable immunodeficiency (CVID) is an immune system disorder that causes you to have low levels of the proteins that help fight infections. If you have CVID, you’ll likely have repeated infections in your ears, sinuses, and respiratory system. You’ll also have an increased risk of digestive disorders, autoimmune disorders, blood disorders, and cancer. CVID can be inherited, or you can develop it during your lifetime.SymptomsThe severity of symptoms can vary greatly between people with CVID. Symptoms of common variable immunodeficiency may appear during childhood or adolescence, though many people don’t experience them until adulthood.If you have CVID, you’ll likely experience repeated infections before being diagnosed. The most common types of infections include pneumonia, sinusitis, ear infections and gastrointestinal infections.CausesIn the vast majority of CVID cases, the cause is unknown. In around 10% of people with CVID, a genetic mutation has been identified. Researchers believe that the condition is caused by a combination of both environmental and genetic factors. As of 2023, the environmental factors are unclear.Updated: 2023-03-03Publication Date: 2022-01-06

OverviewX-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh)—also called XLA—is an inherited (genetic) immune system disorder that reduces your ability to fight infections. People with XLA might get infections of the inner ear, sinuses, respiratory tract, bloodstream, and internal organs.XLA affects males almost exclusively, although females can be genetic carriers of the condition. Most people with XLA are diagnosed in infancy or early childhood, after they’ve had repeated infections. Some people aren’t diagnosed until adulthood.SymptomsBabies with XLA generally appear healthy during their first couple months because they’re protected by the antibodies they got from their mothers before birth. When these antibodies clear from their systems, the babies begin to develop often severe, recurrent bacterial infections—such as of the ears, lungs, sinuses, and skin—that can be life-threatening.Male infants born with XLA have:Very small tonsilsSmall or no lymph nodesCausesX-linked agammaglobulinemia is caused by a genetic mutation. People with the condition can’t produce antibodies that fight infection. About 40% of people with the condition have a family member who has it.ComplicationsPeople with XLA can live relatively normal lives and should be encouraged to participate in regular activities for their ages. However, recurrent infections related to XLA will likely require careful attention and aggressive treatment. They can cause organ damage and be life-threatening.Possible complications include:Chronic lung diseaseIncreased risk of certain cancersInfectious arthritisIncreased risk of central nervous system infections from live vaccinesDiagnosisYour doctor will take a medical history to document recurrent infections and do a physical exam. They will order blood tests and possibly recommend genetic testing to confirm the diagnosis.TreatmentThere’s no cure for XLA. The goal of treatment is to boost the immune system, preventing infections and aggressively treating infections that occur.MedicationsMedications to treat XLA include:Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It’s given by infusion into a vein every two to four weeks or by weekly injection.Reactions to gammaglobulin can include headache, chills, backache, and nausea. Reactions are more likely to occur during a viral infection.Antibiotics. Some people with XLA receive continuous antibiotics to prevent infections. Others take antibiotics for bacterial infections longer than people without XLA do.Your doctor will likely recommend that you have follow-up visits every six to 12 months to screen for complications of XLA. You’ll also likely be advised to not get live vaccines, such as live polio, measles-mumps-rubella, or chickenpox vaccines.Updated: 2023-03-02Publication Date: 2022-09-09