50 years later, the cells of the first "bubble baby" are reanalyzed

On the second page of a new article published in PNAS, we can read the term "P10" for "Patient 10". "This number actually refers to Michel, the very first patient to receive a bone marrow transplant in France, in 1972. This baby, only a few months old, was the patient of Prof. Claude Griscelli, a pediatrician, immunologist and co-author of this new study," says Prof. Alain Fischer, Professor of Pediatric Immunology at the Necker-Enfants Malades AP-HP hospital and co-founder of the Imagine Institute with Prof. Claude Griscelli. This patient had a severe combined immunodeficiency, meaning that he had no immune system to protect him from external infections. One particular manifestation of this syndrom is a total absence of lymphoid organs (lymph nodes, thymus), biological structures where T-cells are normally produced and reside.

As Professor Claude Griscelli recounts in his book L'enfant sans défenses (Humensciences, March 2021), the bone marrow transplant had spectacular effects on his young patient: "about ten days after the operation, the lymphocytes previously absent from Michel's body appeared. Three months later, the deficit was corrected". This success nevertheless left a bitter taste. In fact, a few months later, Michel died of neurological complications unrelated to the transplant. "The great joy of obtaining a correction of the immune deficiency by the transplant was transformed into an immense disappointment", recalls the pediatrician. Nevertheless, this pioneering operation opened the field to a medical practice that saved and continues to save many patients with immune deficiencies.

In this new study published in PNAS, Prof. Alain Fischer's team reanalyzed Michel's biological tissues as well as MRIs of nine patients thanks to Dr. Laureline Berteloot, from the radiology department of the Necker-Enfants Malades AP-HP hospital. All of them had received a bone marrow transplant to fix a severe combined immune deficiency due to a mutation of the IL2RG and JAK3 genes. These genes ensure the production of cells involved in the formation of secondary lymphoid organs, allowing a rapid and localized immune response in case of infection. Without transplantation, patients with these mutations do not develop secondary lymphoid organs as they should. But, thanks to the bone marrow transplantation, this is not inevitable.

Cells rediscovered in biological archives 50 years later

"By analyzing MRI scans and cells from different organs of 1972 patient, we have shown that bone marrow transplantation leads to the development of secondary lymphoid structures in the intestine and in the appendix," says Alain Fischer. "We have thus identified a new pathway in the formation of these structures". This study would not have been possible without the rediscovery - by Prof. Thierry Jo Molina's anatomopathology team - of samples from Claude Griscelli's patient, perfectly preserved in the biological archives in the basement of the Necker Hospital, after 50 years of oblivion. Next step? To elucidate the mechanisms underlying the formation of these secondary lymphoid structures.