Genetic Phenomenon Cures Rare Immune Disease

Spontaneous cure achieved in first person documented with WHIM Syndrome.

Spontaneous cure achieved in first person documented with WHIM Syndrome.

A genetic phenomenon generated a cure for a rare immune disease in a study by the National Institutes of Health (NIH).

This phenomenon, called chromothripsis or chromosome shattering, was found to spontaneously cure the first person documented with WHIM syndrome. The disorder is a syndrome of recurrent infections, warts, and cancer, which are caused by the inability of immune cells to exit bone marrow and enter the bloodstream. The disease particularly affects infection-fighting neutrophils.

Researchers in 2003 were able to identify genetic mutations occurring in the CXCR4 gene that are responsible for WHIM syndrome.

The patient, who was the subject of a 1964 study that was the first to describe the disease, reached out as an adult to the NIH to have herself and 2 of her children who also were diagnosed with WHIM syndrome evaluated. The patient’s symptoms resolved when she was in her 30s, which indicates she maintained remission of the disease for approximately 20 years, the study noted.

Researchers from the NIH National Institute of Allergy and Infectious Diseases (NIAID) zeroed in on chromothripsis, which is the sudden fragmentation of a chromosome, as the reason for the cure.

Severe changes such as chromothripsis frequently cause cell death, unless the process confers the kind of survival advantage that occurs during the development of certain types of cancer. Chromothripsis was found to cause a “random and fortuitous” deletion of the mutant CXCR4 gene in the patient, the study authors wrote.

The researchers hypothesize a stem cell lacking the mutant CXCR4 gene survived and at some point repopulated all of the neutrophils, which are now apparently functioning normally in the patient. This was the first study to link chromothripsis with a positive outcome.

While there are no approved treatments for WHIM syndrome, NIAID scientists are currently conducting clinical trials of the drug plerixafor, which has shown promising results. The researchers are also investigating how to apply the findings of the study to enhance bone marrow transplantation, which relies on the donor stem cells repopulating in the recipient.