Cytotoxic T cells in chronic idiopathic neutropenia express restricted antigen receptors

Abstract

Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by female predominance and mostly uncomplicated course. Crucial to CIN pathophysiology is the presence of activated T lymphocytes with myelosuppressive properties in both peripheral blood (PB) and bone marrow (BM). We systematically profiled the T cell receptor beta chain (TRB) gene repertoire in CD8⁺ cells of 34 CIN patients through subcloning/Sanger sequencing analysis of TRBV–TRBD–TRBJ gene rearrangements. Remarkable repertoire skewing and oligoclonality were observed, along with shared clonotypes between different patients, alluding to antigen selection. Cross-comparison of our sequence dataset with public TRB sequence databases revealed that CIN may rarely share common immunogenetic features with other entities, however, the CIN TRB repertoire is largely disease-biased. Overall, these findings suggest that CIN may be driven by long-term exposure to a restricted set of specific CIN-associated antigens.

Keywords:

• Chronic idiopathic neutropenia
• T cell receptor
• antigen selection

Acknowledgements

This work was supported in part by the ENosAI project (code 09SYN-13-880) co-funded by the EU and the General Secretariat for Research and Technology of Greece; the KRIPIS action, funded by the General Secretariat for Research and Technology of Greece; H2020 ‘AEGLE, An analytics framework for integrated and personalized healthcare services in Europe’, by the EU; “MEDGENET” (No. 692298) by the EU.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1324154.

Additional information

Funding

This work was supported in part by the ENosAI project (code 09SYN-13-880) co-funded by the EU and the General Secretariat for Research and Technology of Greece; the KRIPIS action, funded by the General Secretariat for Research and Technology of Greece; H2020 ‘AEGLE, An analytics framework for integrated and personalized healthcare services in Europe’, by the EU; “MEDGENET” (No. 692298) by the EU.