Myeloablative autologous haematopoietic stem cell transplantation resets the B cell repertoire to a more naïve state in patients with systemic sclerosis.
Myeloablative autologous haematopoietic stem cell transplantation resets the B cell repertoire to a more naïve state in patients with systemic sclerosis.
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DOI：
10.1136/ard-2021-221925
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发表时间：
2023-03
影响因子：
27.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在硬皮病：环磷酰胺或移植（SCOT）试验中，最近证实清髓性自体造血干细胞移植（HSCT）在治疗弥漫性皮肤系统性硬化症（dcSSc）方面优于环磷酰胺（CYC）。由于先前已在dcSSc中描述了B细胞区室的失调，我们试图了解清髓性自体HSCT与CYC相比的作用。我们对参加SCOT试验的dcSSc患者的外周血免疫球蛋白重链（IGH）进行了测序。清髓性自体HSCT与携带低突变率的IgM同种型抗体持续增加相关。清髓性自体HSCT后IGH组克隆表达减少。此外，我们发现dcSSc患者免疫球蛋白重链V基因5-51使用不足，清髓性自体HSCT治疗后使用正常，但CYC治疗后未正常。总之，这些发现表明，清髓性自体HSCT将IGH库重置为以表达IgM的B细胞为特征的更幼稚的状态，提供了消除致病性B细胞的可能机制，这可能有助于HSCT在治疗dcSSc中优于CYC。
Myeloablative autologous haematopoietic stem cell transplant (HSCT) was recently demonstrated to provide significant benefit over cyclophosphamide (CYC) in the treatment of diffuse cutaneous systemic sclerosis (dcSSc) in the Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial. As dysregulation of the B cell compartment has previously been described in dcSSc, we sought to gain insight into the effects of myeloablative autologous HSCT as compared with CYC. We sequenced the peripheral blood immunoglobulin heavy chain (IGH) repertoires in patients with dcSSc enrolled in the SCOT trial. Myeloablative autologous HSCT was associated with a sustained increase in IgM isotype antibodies bearing a low mutation rate. Clonal expression was reduced in IGH repertoires following myeloablative autologous HSCT. Additionally, we identified a underusage of immunoglobulin heavy chain V gene 5–51 in patients with dcSSc, and usage normalised following myeloablative autologous HSCT but not CYC treatment. Together, these findings suggest that myeloablative autologous HSCT resets the IGH repertoire to a more naïve state characterised by IgM-expressing B cells, providing a possible mechanism for the elimination of pathogenic B cells that may contribute to the benefit of HSCT over CYC in the treatment of dcSSc.
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影响因子：
7.3
作者：
Soto L;Ferrier A;Aravena O;Fonseca E;Berendsen J;Biere A;Bueno D;Ramos V;Aguillón JC;Catalán D
通讯作者：
Catalán D
影响因子：
7.5
作者：
Arruda, Lucas C. M.;Malmegrim, Kelen C. R.;Oliveira, Maria Carolina
通讯作者：
Oliveira, Maria Carolina
影响因子：
48
作者：
Shugay, Mikhail;Britanova, Olga V.;Chudakov, Dmitriy M.
通讯作者：
Chudakov, Dmitriy M.
影响因子：
4.8
作者：
Baraut, J.;Grigore, E. L.;Michel, L.
通讯作者：
Michel, L.
影响因子：
158.5
作者：
Sullivan, K. M.;Goldmuntz, E. A.;Furst, D. E.
通讯作者：
Furst, D. E.