Neutropenia is a condition that affects the amount of neutrophils in a person's blood. It means they have 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 onset

Both of these 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 of these 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 adolescents 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 work-ups
• Manage all affected patients more appropriately

‘Our 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'

— Dr Grigorios Tsaknakis