As humans, weve been living alongside viruses, bacteria, fungi, and other pathogens for as long as weve existedand weve developed pretty hardy immune systems to deal with them. Unfortunately, in rare cases, some people are born with genetic errors in their immune systems that might make even the mildest bug a serious foe. Many of the symptoms of these conditions first start to appear in childhoodeven in infantsbut others dont present themselves until well into adulthood.

Primary immunodeficiency diseases (PIDDs)now commonly referred to as inborn errors of immunity (IEIs)1is a group of genetic diseases that cause the immune system to malfunction,Dusan Bogunovic, PhD, a professor at the Precision Immunology, Mindich Child Health and Development, and Icahn Genomics institutes in New York City, tells SELF.

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For some people, the immune system malfunctions by not mounting enough of a defense against harmful pathogens, which can result in stubborn infections that lead to frequent illnesses. For others, genetic errors can actually cause the immune system tooverfunction, or put up a fight when its not necessary, which can harm the bodys healthy tissues in the process. Some PIDD conditions, such asWiskott-Aldrich syndrome, are characterized by an underperformingand an overperforming immune system, according toXiao Peng, MD, PhD, an assistant professor of genetic medicine and the director of the Genetics of Blood and Immunity Clinic at Johns Hopkins University School of Medicine. So not only is the immune system insufficiently capable of attacking the things that it should be, sometimes it likes to go rogue and attack the things that it shouldnt be, she tells SELF.

All of this is to say that the immune system is undeniably complex, and experts are still learning about all of the genes involved in PIDDs. Heres what you should know about this umbrella of diseasesincluding the kinds of symptoms that might be worth exploring further.

Most PIDDs are caused by an erroror several errorsin a persons genes, Dr. Peng says. For example, they may have inherited damage to a variant in a single gene.1 In turn, they may experience frequent infections or chronic inflammation, and this can set the stage for serious health problems, Dr. Bogunovic saysall because the immune system isnt quite working right.

These diseases also run on a spectrum, Dr. Peng says. On the most severe end, there are cases likeDavid Vetter, a young boy from Texas who had severe combined immunodeficiency (SCID); he made national news because he had to live in a plastic bubble to protect himself from a number of infectious pathogens until he died at age 12. (Newborns are routinely screened for SCID, among a few other PIDDs.2) Other PIDDs, however, may only make a person more likely to experience complications to a very specific type of pathogen that they dont get exposed to until much later in life, if at all.

It really depends on the person. Even if two people are diagnosed with the same PIDD, one person may end up getting very sick, while another lives a generally healthy life. Some people might have antibody deficiencies that you can measure on a lab test, but [they] never get super sick, Dr. Peng says. That speaks to the fact that what your cells are doing is not necessarily what your body and your environment are putting you at risk for.

That said, one potential indicator that you have an inborn error of immunityis that youre getting severely sick on a regular basiswhich well talk more about in a second.

There are nearly 500 different PIDDs that experts are aware of, and that number is growingmore than 100 new gene errors that contribute to these diseases are discovered every year, according to Dr. Peng.3

When you look at each PIDD individually, each type is relatively rare; collectively, however, these conditions are estimated to affect up to 5 in every 1,000 peopleand certain PIDDs are more frequently diagnosed than others.3 The most common PIDDs affect the bodys ability to produce antibodies, protective proteins that attach to harmful pathogens and remove them from your body. For example, common variable immunodeficiency (CVID), one of the most common PIDDs diagnosed, causes people to have low levels of blood immunoglobulins (another name for antibodies), which can increase their risk of infection, according to theImmune Deficiency Foundation (IDF). Its estimated to affect about 1 in 25,000 people.

Another common PIDD is selective IgA deficiencyas many as 1 in 500 white people have it, but research is lacking to determine the prevalence in people of color. IgA deficiency means an important type of immunoglobulin, immunoglobulin A (IgA), is undetectable in the blood, even though other types of immunoglobulin in the body are detected at normal levels.4 People with IgA deficiency often complain of frequent ear infections, sinusitis, bronchitis, and pneumonia that might not resolve with regular treatment, the IDF notes. They may also have issues with their gut health (including gastrointestinal infections or chronic diarrhea), or have autoimmune conditions, Dr. Peng says, like celiac disease, lupus, or rheumatoid arthritis.

Remember: Not everyone who is diagnosed with PIDDs gets sick a lotplenty of people who have the selective IgA deficiency dont end up seeing the doctor any more often than other folks, while others end up severely ill. Doctors arent sure why that is yet.

When it comes to PIDDs, the biggest red flags include:

Other possible symptoms of PIDDs include digestive issues, delayed growth or development, or inflammation of the internal organs, according to the Mayo Clinic.

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 dont appear until later in a persons life, primary care doctors arent 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, thats 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 persons 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.

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 theMayo 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 therapytypically an IV treatmentcan help replace the lacking proteins.

This can be done via a bone marrow or stem cell transplant.6 For astem 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 patients 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 persons 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. Youre basically knocking out all of the persons immune defenses, putting them at incredible risk for infection before you give them back someone elses stem cells, she says. Even after the cells have been transferred to the person receiving the transplant, it takes time for whats essentially a brand-new immune system to reach fighting capacity. Unfortunately, theres also a risk that the donors new cells will view the recipients 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.

Unlike a stem cell transplant, in gene therapy, technology is used to extract a patients own stem cells, edit the PIDD-related genetic error out of a persons 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 severalclinicaltrials that are currently testing these therapies on humans. According to theImmune 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.

Finally, many people reduce their risk of infection with the basic protective protocols youre probably already familiar with: practicing good hygiene like handwashing, eating well, exercising regularly, and avoiding people who are actively sick, the Mayo Clinic notes.

I think a lot of it is just providing families with information about the nature of that particular immune disease and what their risks are and what situations they need to be a little bit more vigilant [about], Dr. Peng says. Its crucial to find balance too, to make sure their lives dont become entirely about avoidance. Some of the most common sense, simple things are also the most useful things.

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4 Big Things You Should Know About Primary Immunodeficiency Diseases - Self