Child-bubble: what is it? where does this immune deficiency come from? how to handle it?

Bubble children, or bubble babies, for the youngest, are children whose immune system does not work – or at least not enough. In question ? A rare genetic disease called severe combined immunodeficiencywhich affects on average one in 200,000 births each year, according to Inserm (source 1).

Baby bubbles refer to children whose immune defenses are strongly weakened, or even non-existent, which makes them very vulnerable. So vulnerable that they must be placed in a sterile and isolated environment to avoid any risk of potentially fatal infection. The slightest microbe can indeed be fatal to them.

For their protection, the bubble children are placed in confined spaces, separated from their parents and deprived of contact (caresses, hugs, kisses). The first case – at least the first case taken care of in a hospital environment – dates back to about fifty years ago. At the time, these sanitized spaces took the form of giant plastic bubbles, hence the name “baby bubbles”. Today, most of the “bubbles” have given way to large filtered air cabinsas is the case at Necker Hospital.

As stated above, most bubble babies suffer from a genetic condition called severe combined immunodeficiency (SCID) linked to the X chromosome. It is a “rare syndrome, characterized by a lack of function of certain cells of the immune system, normally responsible for protecting the body from microbial attacks”, explains Inserm.

This immunodeficiency is most often innate and genetic : bone marrow stem cells, which have trouble differentiating between T cells and NK cells. But it can also be linked to an abnormality in the synthesis of cytokines. In fact, little patients are very vulnerable to any form of infection, even the most benign, such as ENT infections, lung infections, skin infections, etc. Their risk of developing cancer is also higher.

Note: the age at which recurrent infections begin is important and sheds light on the cause, recalls Dr. James Fernandez in an article published in April 2021 in the MSD Manual (source 2):

• if symptoms occur before the age of 6 months, this suggests a T cell abnormality, as maternal antibodies usually protect for the first 6-9 months.
• if symptoms occur between 6 and 12 monthsthis may suggest combined B and T cell abnormalities or B cell abnormality, which become evident when maternal antibodies disappear (around 6 months of age).
• if symptoms occur within more than 12 monthsthis suggests B cell deficiency or secondary immune deficiency.

If there is a known immune deficiency in a family, its members can indeed carry out a search for the mutated gene before any conception. This makes it possible to assess the risks of transmitting the disease or of being affected by it.

But a child can also be born with this particularity without his parents being visibly affected by it, for example:

• if his mother unknowingly carries a diseased gene on her X chromosome;
• if one of the parents is a carrier of recessive diseased genes (which are only expressed if the associated gene on the second chromosome is also mutated);
• if the gene mutates during the formation of the embryo.

Immune failure exposes children to attacks of many pathogens (bacteria, viruses, microscopic fungi, parasites, etc.). The bubble children are therefore prey to:

• more infections;
• to more severe infections;
• a high rate of relapses or recurrences;
• with a longer healing time.

As stated earlier, these “symptoms” can appear soon after birth, or during infancy, from 9 to 12 months. In the mildest forms, they may even go unnoticed until adulthood. But in the medium to long term, the people concerned are more exposed to the risk of developing a autoimmune disease, lymphoma or cancer.

Bubble children benefit from special vaccination recommendations, assessed by a specialist depending on the type of immune deficiency and the treatments in progress, recalls the Vaccination Info Service website (source 3). Generally :

• inactivated vaccines are recommended with suitable regimens, as their effectiveness may be reduced;
• the flu vaccination is recommended every year;
• and live attenuated vaccines are contraindicated. In other words, bubble children cannot be vaccinated:
  – against measles,
  – against mumps,
  – against rubella,
  – against chickenpox,
  – against yellow fever
  – or against tuberculosis.

In addition, the close entourage of children with congenital immunodeficiencies must be up to date with their vaccines to minimize the risk of transmitting an infection to them.

Depending on the nature and severity of the congenital immune deficiency, several types of treatments can relieve bubble babies, such as taking antibiotics to prevent certain infections or treat those that occur and administration of immunoglobulins (antibody), when the immune deficiency is manifested by an antibody deficiency. But these treatments are not curative. The only treatments capable of definitively eliminating congenital immunodeficiency are:

• bone marrow transplantin other words, a transplant of compatible hematopoietic stem cells, ideally from a sibling
• and gene therapywhich repairs the genetic mutation causing SCID.

Note: gene therapy is only available for a very limited number of patients whose state of health does not allow a bone marrow transplant to be considered.

In 1999, the first clinical trials demonstrated that it was possible to treat baby bubbles by gene therapy, indicates Inserm (source 4). This method consists of collect stem cells from the bubble child’s bone marrow, then to correct the mutated gene thanks to a virus whose pathological potential is deactivated, before reinjecting these stem cells into the body, so that they proliferate and allow the immune system to function normally. But these first trials were suspended after some bubble babies, cured, ended up developing leukemia.

Following the development of safer therapeutic vectors, a new clinical trial finally started in 2010. Four years later, in October 2014, the results obtained were the subject of an article in the journal New Englishand Journal of Medicine (source 5). Out of nine patients suffering from X-linked severe combined immunodeficiency and having benefited from the new gene therapy (five French patients and four American patients), seven were then in good health.