Long-lasting, late-onset, and chronic idiopathic neutropenia project
An SWG Grant-supported project initiated by EHA’s Granulocytes and Constitutional Marrow Failure Disorders SWG.
Project team
Project background and aims
This SWG Grant-funded project will help to support an increased knowledge of LLNp, LONp, and CIN.
Neutropenia is a condition that affects the number of neutrophils in a person’s blood, resulting in a low number of these white blood cells.
There are two types of neutropenia that are not categorized as either primary autoimmune neutropenia or the idiopathic neutropenia of infancy.
These are:
- Long-lasting neutropenia (LLNp)—which is a type of neutropenia that lasts for more than the typical period of 24 to 36 months
- Late-onset neutropenia (LONp)—which is a type of neutropenia that has a delayed or a very delayed onse
Both types of neutropenia:
- Are sometimes diagnosed by chance, due to the very mild clinical phenotype
- Do not usually show remission
As shown in a recent paper from our group, both forms might be considered as a unique entity that’s sustained, at least in a little subgroup, by an underlying genetic background.
In both cases, patients show signs of immune dysregulation. This may be present at the beginning, with a tendency to worsen over time (leukopenia, lymphopenia with decreased B and NK cell numbers).
We could speculate that, because they present few symptoms, neutropenias that arise in late infancy or adolescence may be under-diagnosed until adulthood. At that point, they will present as chronic idiopathic neutropenia (CIN).
If this hypothesis is correct, there could be a link that joins neutropenia in children with neutropenia in adults. In this view, any collaboration between pediatricians and adult hematologists is of outstanding importance.
This SWG Grant-funded project will help to create the basis of that connection by supporting increased knowledge of LLNp, LONp, and CIN.
In particular, it will provide information on their:
- Clinical and immunological features
- Genetic background, through the application of the whole-exome sequencing (WES) technique
By furthering knowledge on LLNp, LONp, and CIN, we can help clinicians to:
- Understand the underlying mechanisms of these disorders
- Tailor diagnostic workups
- Manage affected patients more appropriately
The research hypothesis is that:
- A constitutional/congenital background might exist in some CIN cases
- The CIN phenotype can be also an epiphenomenon of immune dysregulation and associated underlying disorders
This grant will significantly contribute towards delineating the pathogenesis of CIN through the:
- Identification of variants with high probability to display a causative role
- Indication of a potential continuum in the spectrum of CIN from childhood to adulthood, at least in some cases
- Identification of cases with common genetic background
Project updates
You can find out more about the status of this project by reading the latest update from Dr Grigorios Tsaknakis.