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多抗原骨髓瘤特异性T细胞检测在单克隆丙种球蛋白病患者中的预后相关性

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies.

作者信息

Lagreca Ivana, Nasillo Vincenzo, Barozzi Patrizia, Castelli Ilaria, Basso Sabrina, Castellano Sara, Paolini Ambra, Maccaferri Monica, Colaci Elisabetta, Vallerini Daniela, Natali Patrizia, Debbia Daria, Pirotti Tommaso, Ottomano Anna Maria, Maffei Rossana, Bettelli Francesca, Giusti Davide, Messerotti Andrea, Gilioli Andrea, Pioli Valeria, Leonardi Giovanna, Forghieri Fabio, Bresciani Paola, Cuoghi Angela, Morselli Monica, Manfredini Rossella, Longo Giuseppe, Candoni Anna, Marasca Roberto, Potenza Leonardo, Tagliafico Enrico, Trenti Tommaso, Comoli Patrizia, Luppi Mario, Riva Giovanni

机构信息

Section of Hematology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, AOU Modena, 41124 Modena, Italy.

Diagnostic Hematology and Clinical Genomics, Department of Laboratory Medicine and Pathology, AUSL/AOU Modena, 41124 Modena, Italy.

出版信息

Cancers (Basel). 2023 Feb 3;15(3):972. doi: 10.3390/cancers15030972.

DOI:10.3390/cancers15030972
PMID:36765928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913154/
Abstract

Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease ( < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.

摘要

多发性骨髓瘤(MM)通常起源于潜在的前驱疾病,即意义未明的单克隆丙种球蛋白病(MGUS)和冒烟型多发性骨髓瘤(SMM)。目前的预后模型采用了与克隆性浆细胞主要特征相关的经过验证的风险因素,以评估进展为MM的长期概率。此外,测量保护性MM特异性T细胞反应的新的预后免疫参数,有助于识别进展时间较短的患者。在本报告中,我们描述了一种基于酶联免疫斑点技术的新型多抗原骨髓瘤特异性(MaMs)T细胞检测方法,可同时评估T细胞对十种不同MM相关抗原的反应。在33例MGUS或SMM患者的长期随访(平均28个月)期间进行这种十抗原骨髓瘤特异性免疫检测时,能够显著区分稳定疾病与进展性疾病(P<0.001),且与梅奥诊所风险类别无关。在此,我们报告了首次临床经验,表明一种广泛的(多抗原)、标准化的(与患者HLA无关)MM特异性T细胞检测方法可作为一种有前景的预后工具,常规应用于MGUS/SMM患者的随访。需要开展更大规模的研究来改进抗原组,并进一步探索MaMs检测在单克隆丙种球蛋白病患者风险评估中的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/51c97acc4b68/cancers-15-00972-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/62539cfb47b8/cancers-15-00972-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/a2821b8a0b6e/cancers-15-00972-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/0f4781625c19/cancers-15-00972-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/fd3dd59cc937/cancers-15-00972-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/51c97acc4b68/cancers-15-00972-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/62539cfb47b8/cancers-15-00972-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/a2821b8a0b6e/cancers-15-00972-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/0f4781625c19/cancers-15-00972-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/fd3dd59cc937/cancers-15-00972-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/9913154/51c97acc4b68/cancers-15-00972-g005.jpg

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本文引用的文献

1
In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present From Diagnosis in Tiny, Undetectable Subclonal Populations.在多发性骨髓瘤中,从诊断时就存在于微小、难以检测的亚克隆群体中的复发时观察到的高风险次级遗传事件。
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