Cited by 56Complement system in diseasesBlood groups and transfusionT-cell and B-cell Immunology

Highly homologous T-cell receptor beta sequences support a common target for autoreactive T cells in most patients with paroxysmal nocturnal hemoglobinuria

Gargiulo, Lucia, Lastraioli, Sonia, Cerruti, Giannamaria, Serra, Martina, Loiacono, Fabrizio, Zupo, Simona, Luzzatto, Lucio, Notaro, Rosario·2007·Blood

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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Crossref · 10.1182/blood-2006-10-052381

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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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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)
Venue
Blood
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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