High-throughput RNA sequencing of the T cell receptor alpha and beta chains for simultaneous clonality and biological analyses in Sezary syndrome
Blanco, Gonzalo (Hospital del Mar (Barcelona, Catalunya))
López-Aventín, Daniel (Universitat Autònoma de Barcelona. Departament de Medicina)
Pujol Vallverdú, Ramón M (Hospital del Mar (Barcelona, Catalunya))
Gómez-Llonín, Andrea (Hospital del Mar (Barcelona, Catalunya))
Puiggros, Anna (Hospital del Mar (Barcelona, Catalunya))
López-Sánchez, Manuela (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Estrach, Teresa (Hospital Clínic i Provincial de Barcelona)
Garcia Muret, Maria Pilar (Institut d'Investigació Biomèdica Sant Pau)
Lopez-Lerma, Ingrid (Hospital Universitari Vall d'Hebron)
Servitje, Octavio (Hospital Universitari de Bellvitge)
Bellosillo Paricio, Beatriz (Hospital del Mar (Barcelona, Catalunya))
Muro, Manuel (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Espinet, Blanca (Hospital del Mar (Barcelona, Catalunya))
Rabionet, Raquel (Instituto de Salud Carlos III)
Gallardo, Fernando (Hospital del Mar (Barcelona, Catalunya))

Data:	2023
Resum:	Previous investigations pointed out a role for antigen stimulation in Sezary syndrome (SS). High-throughput sequencing of the T cell receptor (TR) offers several applications beyond diagnostic purposes, including the study of T cell pathogenesis. We performed high-throughput RNA sequencing of the TR alpha (TRA) and beta (TRB) genes focusing on the complementarity-determining region 3 (CDR3) in 11 SS and one erythrodermic mycosis fungoides (MF) patients. Five psoriasis patients were employed as controls. Peripheral blood CD4 + cells were isolated and RNA sequenced (HiSeq2500). High-resolution HLA typing was performed in neoplastic patients. Highly expanded predominant TRA and TRB CDR3 were only found in SS patients (median frequency: 94. 4% and 93. 7%). No remarkable CDR3 expansions were observed in psoriasis patients (median frequency of predominant TRA and TRB CDR3: 0. 87% and 0. 69%, p < 0. 001 compared to SS). CDR3 almost identical to the predominant were identified within each SS patient and were exponentially correlated with frequencies of the predominant CDR3 (R 2 = 0. 918, p < 0. 001). Forty-six different CDR3 were shared between SS patients displaying HLA similarities, including predominant TRA and TRB CDR3 in one patient that were found in other three patients. Additionally, 351 antigen matches were detected (Cytomegalovirus, Epstein-Barr, Influenza virus, and self-antigens), and the predominant CDR3 of two different SS patients matched CDR3 with specificity for Influenza and Epstein-Barr viruses. Besides detecting clonality, these findings shed light on the nature of SS-related antigens, pointing to RNA sequencing as a useful tool for simultaneous clonality and biological analysis in SS. We performed RNA sequencing of TR alpha (TRA) and beta (TRB) in peripheral blood CD4 + T cells from Sezary Syndrome (SS) and psoriasis patients (PS) employed as controls and found correlated (A) and highly expanded predominant TRA and TRB complementarity-determining regions 3 (CDR3) only in SS patients (B). CDR3 almost identical to the predominant were identified within each SS patient and were exponentially correlated with frequencies of the predominant CDR3 (C), and shared CDR3 (D) enriched in antigen matches between different patients (including CMV, Epstein-Barr virus, Influenza virus and self-antigens) were also detected (E). Besides detecting clonality, these findings shed light on the nature of SS-related antigens, pointing to RNA sequencing as a useful tool for simultaneous clonality and biological analysis in SS.
Ajuts:	Generalitat de Catalunya 2021/SGR025 Generalitat de Catalunya 2017/SGR738 Generalitat de Catalunya 2017/SGR437 Instituto de Salud Carlos III PI21/00390 Instituto de Salud Carlos III PI18/00021
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Antigen restriction ; Complementarity determining region ; Mycosis fungoides ; RNA sequencing ; Sezary syndrome ; T cell receptor
Publicat a:	Journal of Clinical Laboratory Analysis, Vol. 37 (december 2023) , ISSN 1098-2825

DOI: 10.1002/jcla.24982
PMID: 38115685

9 p, 824.5 KB

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