Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria
Abstract
Deficiency of glycosylphosphatidylinositol (GPI)-anchored molecules on blood cells accounts for most features of paroxysmal nocturnal hemoglobinuria (PNH) but not for the expansion of PNH (GPI(-)) clone(s). A plausible model is that PNH clones expand by escaping negative selection exerted by autoreactive T cells against normal (GPI(+)) hematopoiesis. By a systematic analysis of T-cell receptor beta (TCR-beta) clonotypes of the CD8+ CD57+ T-cell population, frequently deranged in PNH, we show recurrent clonotypes in PNH patients but not in healthy controls: 11 of 16 patients shared at least 1 of 5 clonotypes, and a set of closely related clonotypes was present in 9 patients. The presence of T-cell clones bearing a set of highly homologous TCR-beta molecules in most patients with hemolytic PNH is consistent with an immune process driven by the same (or similar) antigen(s)-probably a nonpeptide antigen, because patients sharing clonotypes do not all share identical HLA alleles. These data confirm that CD8+ CD57+ T cells play a role in PNH pathogenesis and provide strong new support to the hypothesis that the expansion of the GPI(-) blood cell population in PNH is due to selective damage to normal hematopoiesis mediated by an autoimmune attack against a nonpeptide antigen(s) that could be the GPI anchor itself.
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In the majority of AA patients, glycosylphosphatidylinositol-specific T cells can be detected.
“In the majority of AA patients, glycosylphosphatidylinositol-specific T cells can be detected.61,62”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [61]
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Sica, M. (2008) · Università degli Studi di Napoli Federico II · doi:10.6092/unina/fedoa/2817
Daniels, G. L. (2013) · doi:10.1002/9781118493595.ch19
Rare Bone Marrow Failure Conditions
Visconte, V., & Tiu, R. V. (2012) · Wiley eBooks · doi:10.1002/9781118464557.ch46
Visweshwar, N., Jaglal, M. V., Booth, C. L., Griffin, P. T., & Laber, D. A. (2016) · Annals of Hematology · doi:10.1007/s00277-016-2752-5
Clonal Origin and Clonal Selection in PNH
Luzzatto, L. (2017) · Springer eBooks · doi:10.1007/978-4-431-56003-6_12
Self-citationBone Marrow Failure in Paroxysmal Nocturnal Hemoglobinuria
de Latour, R. P., & Risitano, A. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804152-9.00014-2
Zeng, L., Wang, C., Li, L., Liu, Z., Wang, H., Chen, Y., Wu, J., Wang, G., Li, L., Liu, H., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3154035/v1
Clonal expansion mechanisms in paroxysmal nocturnal hemoglobinuria
Kinoshita, T. (2026) · International Journal of Hematology · doi:10.1007/s12185-026-04167-5
Paroxysmal Nocturnal Hemoglobinuria: Bone Marrow Failure and Beyond
Risitano, A. M., Frieri, C., Prata, P. H., & de Latour, R. P. (2026) · Springer eBooks · doi:10.1007/978-3-032-02386-5_14
- Authors
- Gargiulo, L., Lastraioli, S., Cerruti, G., Serra, M., Loiacono, F., Zupo, S., Luzzatto, L., & Notaro, R.
- Affiliations
- Laboratory of Human Genetics and
- Laboratory of Diagnostics of Lymphoproliferative Disorders, Istituto Nazionale per la Ricerca sul Cancro (IST), Genoa, Italy;
- Tumour Institute of Tuscany (IT)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-06-01
- Volume
- 109
- Issue
- 11
- Pages
- 5036-5042
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2008360827
- Cited by
- 56
- References
- 54
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 4 · 2016: 3 · 2014: 3 · 2013: 3 · 2012: 7
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministero dell'Università e della Ricerca
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- paroxysmal nocturnal hemoglobinuria, CD8+CD57+ T cells, autoreactive T cells, negative selection, glycosylphosphatidylinositol deficiency, autoimmune hemolysis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Autoimmune Diseases, Female, Hemoglobinuria, Paroxysmal, HLA Antigens, Humans, Male, Middle Aged, T-Lymphocytes, Receptors, Antigen, T-Cell, alpha-beta, Glycosylphosphatidylinositols, CD8-Positive T-Lymphocytes, CD57 Antigens
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