LRBA deficiency

LRBA deficiency is a disorder of immune regulation, the system of checks that stops the immune system from attacking the body. It is sometimes called LATAIE disease. The name is short for LRBA deficiency with autoantibodies, regulatory T cell defects, autoimmune infiltration and enteropathy (gut disease).

A healthy immune system needs both a gas pedal and a brake. One key brake is a protein called CTLA-4. It sits on T cells, including regulatory T cells, the white blood cells that tell the rest of the immune system to stand down. The LRBA protein moves and recycles CTLA-4 inside the cell. Without LRBA, CTLA-4 is broken down too fast, so the brake is weak.

The result is two problems at once. The immune system does not fight germs well (immune deficiency), and it attacks the body’s own tissues (immune dysregulation). LRBA deficiency was first described in 2012.

LRBA deficiency is caused by changes in both copies of the LRBA gene. It is inherited in an autosomal recessive way. Each parent usually carries one changed copy and has no symptoms. When both parents are carriers, each child has a 1 in 4 chance of being affected, no matter what happened in earlier pregnancies.

A child who inherits only one changed copy does not develop LRBA deficiency. Almost everyone with two changed copies does become ill. The condition is seen more often when parents are related to each other, and most reported patients come from Asian countries.

Symptoms usually begin in early childhood, often by preschool age. Many children have repeated ear, sinus and chest infections, including pneumonia. Antibody levels are often low, and vaccines may not protect well. Infections with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) are more likely.

Autoimmune problems are the main feature. The immune system can destroy red blood cells or platelets. It can also attack the thyroid, the pancreas (causing type 1 diabetes), the skin, the joints or the eyes. Long-lasting diarrhea from gut inflammation (enteropathy) is very common and can cause weight loss and poor growth. Lymph nodes, the spleen and the liver can swell, and immune cells can crowd into the lungs, brain and other organs.

The course varies a lot, even within one family. Some people are severely affected, while others have few symptoms. The risk of lymphoma, a cancer of immune cells, is higher, so care teams watch closely.

Doctors think of LRBA deficiency in a child with repeated sinus and lung infections together with autoimmune problems. Other clues are long-lasting diarrhea, weight loss or poor growth, and a large spleen or swollen lymph nodes. Immune cells may also crowd into organs such as the lungs, gut or brain. Some people are first diagnosed with common variable immunodeficiency (CVID).

First tests include a complete blood count and antibody levels, where IgG and IgA are usually low. Flow cytometry, a test that counts the different kinds of white blood cells, is also used. Many people have few regulatory T cells and few switched memory B cells, a type of B cell. Scans or biopsies may check organs for immune cell build-up. A specialized lab test can show whether the LRBA protein is missing from the cells.

A genetic test confirms the diagnosis by finding changes in both copies of the LRBA gene. Getting there can take years. A 2025 report from a children’s hospital in Mumbai, India, notes that in 212 published patients, diagnosis came about 5 years after the first symptoms.

Treatment depends on which problems a person has. To prevent infections, many people get immunoglobulin (Ig) replacement, which is antibodies taken from donated plasma. Some also take antibiotics to prevent infections. The goal is to stop repeated infections from damaging the organs.

To calm the immune attack, care teams often use abatacept. It is a lab-made form of CTLA-4, so it can stand in for the weak brake. In 2015, researchers reported a dramatic and lasting improvement in patients with LRBA deficiency who took it. In the United States, abatacept is approved for some kinds of arthritis and to help prevent graft-versus-host disease after a transplant. It is not approved for LRBA deficiency, so this use is off-label. Other medicines include sirolimus, steroids and rituximab.

These medicines control the disease but do not cure it. In an international study of 76 patients, only 5 of the 43 living patients who had not had a transplant were off immune-calming medicines. A donor stem cell transplant (allogeneic transplant) replaces the immune system with the donor’s. It is the only treatment reported to cure LRBA deficiency. It is used mainly for severe disease, and its risks are weighed against a lifetime of disease activity, medicines and cancer risk.

Once infections, inflammation and autoimmunity are managed, many people are able to lead fairly normal lives, and they do not need to be kept apart from others. Because the disease can affect many organs, care often involves several specialists and regular checkups.

Treatment can mean regular immunoglobulin and abatacept, often for years. Abatacept is given as a shot under the skin each week or as a drip into a vein every 4 weeks. Families may also face questions about brothers and sisters and about future pregnancies. NIH patient information encourages families to talk openly about the condition, including with brothers and sisters who may worry.

A transplant means strong conditioning treatment, weeks in the hospital and months of checks for infection and graft-versus-host disease, when donor immune cells attack the body. In the international study, all deaths after transplant happened early and were caused by the transplant itself. Lung disease and heavier disease before transplant were linked to poorer results.

A transplant needs blood-forming cells from a donor whose tissue type (HLA) closely matches the patient’s. Brothers and sisters are often checked first. Each full brother or sister has a 1 in 4 chance of also having LRBA deficiency. European transplant guidelines say family donors should be checked for the family’s gene changes.

A relative who carries only one changed copy is healthy and can be a donor. In a two-center series of 7 transplants, 4 of the 6 family donors were carriers, and 1 transplant used an unrelated donor. Using a carrier donor did not change how well the transplants worked.

When no family member matches, a matched unrelated volunteer from a registry is an option. EBMT’s 2025 recommendations for children list a matched unrelated donor as a standard option for primary immunodeficiencies, though they do not name LRBA deficiency separately. Joining a registry cannot promise a match for any one person, but more volunteers widen the choices.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

Outlook depends most on how severe the disease is and which organs are involved. In the largest international study, 76 patients were followed for a median of 10 years. Those who had a transplant and survived had lower disease activity than those on long-term medicines. Among people on medicines, those who took abatacept or sirolimus did better than those on other treatments.

The risks of transplant were real. All deaths after transplant happened early and were caused by the procedure. Heavier disease, a longer wait before transplant and lung involvement were linked to poorer results. Of the 17 survivors, 12 were in full or good partial remission without any treatment. In a later study from Turkey, transplant and abatacept gave similar chances of survival.