National Institute of Allergy and Infectious Diseases | health information 

LRBA Deficiency

NIAID

LRBA deficiency is a rare genetic disorder of the immune system caused by mutations in the 

LRBA gene. This disease impairs normal regulation of the immune system and results in excessive 

numbers of immune cells called lymphocytes (lymphoproliferation), autoimmunity, low levels of 

antibodies (hypogammaglobulinemia), and recurrent infections. Sometimes the excess lymphocytes 

enter and accumulate in organs where lymphocytes typically are not present in large numbers, 

which can cause a variety of symptoms. This infiltration is most common in the gut, lungs, and brain. 

LRBA deficiency also may increase a 

person’s risk of lymphoma, a type of 

cancer. LRBA deficiency is sometimes 

called LATAIE disease (LRBA deficiency with autoantibodies, regulatory 

T cell defects, autoimmune infiltration, and enteropathy). LRBA deficiency is diagnosed based on clinical 

symptoms, laboratory findings, and 

genetic testing.

Genetics primer: All the cells in the body contain instructions on how to 

do their job. These instructions are packaged into chromosomes, each of 

which contains many genes. Genes are units of inheritance that are made 

up of DNA and encode proteins. An error, or mutation, in a gene can cause 

disorders such as LRBA deficiency. Credit: NIAID

Genetics and Function

LRBA deficiency is caused by mutations in the LRBA gene, 

which stands for “lipopolysaccharide-responsive vesicle trafficking, beach- and anchor-containing.” The LRBA gene provides 

instructions for production of the large LRBA protein. The LRBA 

protein participates in recycling specific cellular components, 

including a “brake” on the immune system called CTLA4. CTLA4 

helps slow down or decrease the action of the immune system. 

A healthy immune system needs to be able to both ramp up and 

slow down, much like a car controlled by gas and brake pedals. 

In LRBA deficiency, this “brake” is recycled too quickly and 

does not have sufficient opportunity to keep the immune system’s 

activity under control. LRBA defects affect multiple immune cell 

types and can lead to both autoimmunity and immunodeficiency.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Institute of Allergy and Infectious Diseases

Model depicting the function of CTLA4 

and its regulation by LRBA. Credit: NIAID
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Inheritance

LRBA deficiency is inherited in an autosomal recessive 

manner. In autosomal recessive inheritance, two copies of 

an abnormal gene—one copy from each parent—must be 

present for the disease to develop. Typically, this means 

that both parents of an affected child carry one abnormal 

gene and are unaffected by the disease. This also explains 

why some cases of LRBA deficiency have involved homozygosity (identical mutations in the mother and father) 

related to consanguinity (when parents are related to each 

other) or geographically isolated communities.

When both parents have one abnormal copy of the LRBA

gene, each child has a 25 percent, or one in four, chance 

of being affected by the disease. This risk is independent of 

prior children’s status. For example, if the first two children 

in a family are affected, the next child has the same 25 percent risk of inheriting the mutation. All affected individuals 

have two abnormal copies of LRBA. Children who inherit 

only one abnormal copy of LRBA will not develop LRBA

deficiency, although it is possible for them to have affected 

children, particularly if they marry within the family.

In this example, two unaffected parents each 

carry one copy of a gene mutation for an 

autosomal recessive disorder. They have one 

affected child and three unaffected children, two 

of which carry one copy of the gene mutation. 

Credit: U.S. National Library of Medicine

Clinical Symptoms

LRBA deficiency is characterized by lymphocytic infiltration 

of non-lymphoid organs (such as the gut, lungs, and brain), 

autoimmunity, hypogammaglobulinemia, and lymphoproliferation. Lymphocytic infiltration of the gut, which causes 

intestinal disease (enteropathy), is by far the most common. 

The lymphoproliferation leads to enlargement of the lymph 

nodes (lymphadenopathy) and liver and spleen (hepatosplenomegaly). Patients with hypogammaglobulinemia 

are highly susceptible to infections, especially in the upper 

respiratory tract. Autoimmune problems can affect various 

organs and tissues, including:

• Blood: Blood problems may include thrombocytopenia and hemolytic anemia (see the Glossary). 

Thrombocytopenia causes poor blood clotting, and 

bleeding cannot be stopped following minor injuries. 

Anemia may cause a feeling of weakness or fatigue.

• Thyroid: Autoimmune thyroiditis is an inflammation 

of the thyroid, a small gland at the base of the neck. Clinical features of LRBA deficiency. Credit: NIAID
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• Skin: The autoimmune skin disease psoriasis is characterized by red, itchy patches of skin. 

Alternatively, some people with LRBA deficiency have experienced autoimmunity against the 

pigment in their skin, called vitiligo.

• Joints: Autoimmune arthritis causes joint pain and stiffness.

• Eyes: Autoimmune uveitis is inflammation of the middle layer of the eye (called the uvea).

• Pancreas: Autoimmunity against parts of the pancreas can cause type 1 diabetes.

These symptoms are all related to the immune system not being able to slow down when necessary. 

Importantly, the symptoms and course of this disease vary widely. Some people are severely affected, 

whereas others show few symptoms of disease. This “variable expressivity” can be striking, even 

within the same family, and may be explained by differences in lifestyle, exposure to pathogens, 

effectiveness of treatment, or other genetic factors.

Laboratory Findings

The clinical symptoms of LRBA deficiency are caused by immune system abnormalities. Most people 

with LRBA deficiency develop reduced levels of immunoglobulins. People with LRBA deficiency also 

may have low LRBA protein expression in regulatory T cells, overactivation of effector T cells, low 

levels of a certain type of B cell called a switched memory B cell, and progressive loss of circulating 

B cells (see the Glossary for more information about these cell types).

Treatment

Once a diagnosis is made, treatment is based on a person’s clinical condition and may include standard therapies for autoimmune problems and immunoglobulin deficiencies. Some patients have been 

treated with medications that inhibit the immune system pathway that is overactivated in people with 

the disease, medications that impact the recycling of cellular components, or medications that mimic 

the “CTLA4 brake” on the immune system. More research is needed to determine the most effective 

timing and dosage of these medications and to investigate other treatment options. In rare and severe 

cases, bone marrow transplantation also may be an option.

LRBA Deficiency and Your Family

Living with LRBA deficiency can be difficult not only for the person who has it but also for their 

family members. It is important for families to talk openly about LRBA deficiency and about how 

the family is dealing with it so misconceptions can be identified and corrected and children can learn 

to identify and cope with their reactions. Some people with LRBA deficiency have to work hard to 

develop their self-confidence and sense of security. Everyone needs to be reminded that they have 

many positive characteristics, especially when their appearance attracts attention (for example, due 

to large lymph nodes).

Some children who have siblings with LRBA deficiency worry about their brother or sister being in 

pain or dying from the disease. Some think that they may develop symptoms because they look or 
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act like a sibling who has the disease or that the disease is contagious. Some children struggle with 

how much time their parents spend with their sick sibling. Many families benefit from meeting or 

talking to other families affected by the same rare disease. Counseling also can help families cope 

with the challenges of LRBA deficiency.

At the same time, many families say that LRBA deficiency has brought them closer together. Through 

their experiences with the disease and its treatment, family members learn about controllable and 

uncontrollable aspects of life. Although certain aspects of the disease cannot be controlled, how 

a family responds to the stress of any illness is controllable and an important aspect of managing 

LRBA deficiency. Children also learn who they can turn to for support and how to solve problems. 

Acknowledging both the challenges and opportunities that LRBA deficiency presents helps children 

develop resilience.
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Glossary

Arthritis—Painful inflammation and stiffness of the joints.

Autoimmune—Describes a process during which a person’s 

immune system attacks healthy cells, organs, and tissues.

B cells—Immune cells that present antigens to T cells and 

produce antibodies, or immunoglobulins.

Cell—The basic unit of living organisms. Human cells consist of 

a nucleus (control center) and cellular organs, called organelles, 

enclosed by a membrane. Groups of cells with similar structure 

and function form tissues.

Chromosome—A thread-like structure made up of DNA that is 

tightly coiled around supporting proteins. Chromosomes reside 

in the control center, or nucleus, of a cell.

DNA (deoxyribonucleic acid)—A self-replicating material 

present in nearly all living organisms. It is the carrier of genetic 

information.

Effector T cell—A type of immune cell that performs the 

functions of an immune response such as cell killing and 

cell activation.

Enteropathy—Disease of the intestines.

Hemolytic anemia—A condition in which red blood cells are 

destroyed and removed from the bloodstream before their 

normal lifespan is over.

Hypogammaglobulinemia—A type of immune deficiency that 

is characterized by a reduction in all types of gamma globulins, 

or infection-fighting antibodies.

Immune system—A system of biological structures and processes within the body that protects it against “foreign” threats 

such as bacteria or viruses.

Immunodeficiency—A state in which the immune system’s 

ability to fight disease is compromised or entirely absent.

Immunoglobulin—Large Y-shaped proteins, also known as antibodies, produced by immune cells called B cells. The immune 

system uses immunoglobulins to identify and neutralize foreign 

objects such as bacteria. Each immunoglobulin is unique, but 

they fall under general subtypes. Examples of the subtypes 

include IgG, IgA, and IgM.

Lymphoma—A type of blood cancer that occurs when certain 

immune cells start dividing uncontrollably and no longer behave 

like normal immune cells.

Lymphoproliferation—The excessive production or buildup of 

immune cells called lymphocytes.

Mutation—A change in the DNA sequence that is associated 

with disease or susceptibility to disease.

Pathogen—A bacterium, virus, or other microorganism that can 

cause disease.

Psoriasis—A skin disease marked by red, itchy, scaly patches.

Regulatory T cell—A type of immune T cell that monitors and 

regulates the activity of other T cells.

Thrombocytopenia—An abnormally low number of platelets in 

the blood.

Thyroiditis—A condition in which the thyroid is inflamed, often 

due to being attacked by a person’s own immune system. The 

thyroid is a small gland at the base on the neck, below the 

Adam’s apple.

September 2016

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