A new study in which researchers from the Sant Joan de Déu Hospital in Barcelona and the Virgen del Rocío Hospital in Seville have participated has made it possible to identify a new rare disease associated with a genetic alteration. The study was led by the St. Anna Children’s Cancer Research Institute, the Austrian Academy of Sciences Research Center for Molecular Medicine and the Medical University of Vienna and its results have been published in the New England Journal of Medicine. .
Researchers have discovered that the disease is related to a mutation in the DOCK11 gene that causes an alteration in the formation of the cellular skeleton, the set of proteins that is responsible for giving cells their shape and ability to move. The abnormality in this gene results in a disorder in the regulation of the immune system that manifests itself from a very young age in the form of persistent inflammation and alteration in the process of formation of blood cells, as well as in the regulation of the immune system. immune.
A child who was seriously ill due to persistent inflammation of unknown origin was first treated by specialists from the Infectious Diseases, Rheumatology and Pediatric Immunology Unit of the Virgen del Rocío Hospital, who performed a genetic study and functional and initial pathology. “His symptomatology did not fit with any known immunodeficiency or autoinflammatory disease, so we contacted Professor Kaan Boztug of the Austrian Academy of Sciences to find out if they had references from other patients in the world who might be in the same situation to achieve a minimum of scientific evidence”, declared Dr. Olaf Neth, head of the Infectious Diseases, Rheumatology and Pediatric Immunology unit at the Virgen del Rocío University Hospital.
“The description of this new entity broadens the spectrum of knowledge and may allow diagnosis in patients with inflammatory diseases whose cause is unknown”
“Despite the extensive study and all the tests carried out, it was not possible to establish a specific diagnosis. It seemed clear that we were facing a clinical situation not previously described. International collaboration was very important to progress in the research and the genetic and functional studies allowed us to determine the suspicion that the mutation detected in the DOCK11 gene could be related to the clinical picture of the child”, explains Dr. Joan Calzada, from the Pediatric Rheumatology team and researcher at the IRSJD of Sant Joan de Déu.
“The functional studies and the biological models developed corroborated the suspicion of being before a new entity. Subsequently, the appearance in other foreign centers of new patients from different families with similar clinical pictures and also with mutations in the same gene has been the piece that completes the puzzle” added Dr. Neth, who is also responsible for the Alterations group Congenital and IBiS Immunity.
How the DOCK11 gene mutation could be treated
Previous studies have shown the importance of the protein produced by the DOCK11 gene for the development of B cells in mouse models. Now, researchers have shown that, to some extent, B cells also do not develop well in humans with DOCK11 deficiency, and at the same time, other immune system cells called T cells are overactivated, explaining the inflammatory state. persistent. “This constant inflammation can cause the accumulation of amyloid protein in the tissues, producing amyloidosis,” says Dr. Laia Alsina, head of the Allergy and Clinical Immunology Service at Hospital Sant Joan de Déu Barcelona.
The details of the function of DOCK11 are “not yet fully understood”, but blood-forming or hematopoietic stem cell transplantation and gene therapy could be therapeutic options to treat this new disease, although they “have yet to be explored”. has highlighted the head of the Pediatric Rheumatology Service of Sant Joan de Déu, Jordi Antón, who adds: “The important thing is that the description of this new entity broadens the spectrum of knowledge and can allow diagnosis in patients with inflammatory diseases whose cause is unknown”.
Kaan Boztug, lead author of the study and scientific director of the St. Anna Children’s Cancer Research Institute, also hopes that other centers will now become aware of this genetic mutation and further explore this disease.
The pediatricians of the Infectious Diseases, Rheumatology and Pediatric Immunology Unit of the Virgen del Rocío University Hospital, Drs. Paula Sanchez Moreno and Marisol Camacho-Lovillo (coordinator of the Pediatric Rheumatology area), also authors of the study, share the same opinion: “The publication in a top-level scientific journal of this series of four cases known to date in the world opens the door for all specialists to have the contacts and keys to better care for new patients who come to our services”, they conclude.
Source: Virgen del Rocío University Hospital and Sant Joan de Déu Hospital
.
