MHC class II deficiency (bare lymphocyte syndrome type II)

MHC class II proteins work like display stands. Immune cells such as B cells, macrophages and dendritic cells use them to show pieces of germs to helper T cells, also called CD4 T cells. Helper T cells then organize the attack and help B cells make antibodies.

In MHC class II deficiency, these display proteins are missing. The thymus, where T cells learn their jobs, also needs them, so helper T cells are low in number. Without the display and the helpers, the body makes few useful antibodies. The condition is a combined immunodeficiency, meaning it weakens both T-cell and B-cell defenses.

Newborn screening for severe combined immunodeficiency (SCID) has found some affected babies but can miss others.

The condition is caused by changes in one of four genes: CIITA, RFX5, RFXANK or RFXAP. These genes act as switches that turn on the MHC class II genes. The class II genes themselves are normal; they are just not switched on.

It is inherited in an autosomal recessive pattern. A child is affected when both copies of the gene carry a change, one from each parent. Parents who each carry one changed copy usually have no symptoms, and each of their children has a one-in-four chance of being affected.

By 2019, more than 100 transplants for it had been reported worldwide, and more patients have been described since. It has been found around the world but is reported more often in North Africa and the Mediterranean region. It cannot be caught from another person.

Symptoms usually start in the first year of life. Babies get repeated infections of the lungs, gut and urinary tract from bacteria, viruses, fungi and Pneumocystis. Severe, long-lasting viral infections are a hallmark of the condition and a leading cause of death.

Many children have chronic diarrhea and cannot absorb food well, so they fall behind in growth. A water-borne parasite called Cryptosporidium can infect the gut and liver and cause chronic liver disease. Repeated infections can also leave lasting lung damage.

Without a transplant, the outlook is poor. In older reports, the average age at death was about 4 years, and very few children reached adulthood. Timing matters because organ damage from infection makes a transplant harder and riskier.

Families often reach the diagnosis after months of infections, hospital stays and worry about weight gain. The weeks before transplant may be spent treating infections and building up nutrition. Care usually brings together immunologists, lung and gut specialists, dietitians and the transplant team.

A transplant means conditioning treatment, a long hospital stay and months of close follow-up for infection, graft failure and graft-versus-host disease. Viral infections are a particular concern before and after transplant. Care is usually given at a specialist center, which may be far from home.

After a successful transplant, children still need follow-up for gut health, growth and immune checks. Parents may want genetic counseling before another pregnancy.

The transplant replaces the child’s blood-forming stem cells with a donor’s, so new immune cells can display germ signals properly. Graft-versus-host disease brings no benefit in this condition, so the best-matched donor is preferred. A matched brother or sister is usually the first choice, after testing shows they are not affected.

If no family donor matches, specialists search national and international registries for an unrelated donor. Partly matched (haploidentical) parents and cord blood are other options at experienced centers. In the UK center’s recent results, children did well with matched family, unrelated and haploidentical donors, though the numbers were small.

Because infections and organ damage build up over time, experts advise starting the transplant process as soon as possible after diagnosis. That can make an unrelated donor search urgent. Joining a registry cannot promise a match for any one child, but it widens the choices families have.