Farge Dominique, Henegar Corneliu, Carmagnat Maryvonnick, Daneshpouy Marjan, Marjanovic Zora, Rabian Claire, Ilie Doina, Douay Corinne, Mounier Nicolas, Clave Emmanuel, Bengoufa Djaouida, Cabane Jean, Marolleau Jean Pierre, Gluckman Eliane, Charron Dominique, Toubert Antoine
Hôpital Saint-Louis, Paris, France.
Arthritis Rheum. 2005 May;52(5):1555-63. doi: 10.1002/art.21036.
To analyze hematopoietic and immune reconstitution after autologous hematopoietic stem cell transplantation (HSCT) in 7 patients with systemic sclerosis (SSc).
Two groups of patients were retrospectively constituted according to whether they had a favorable clinical response (group A; n = 4) or no response or a relapse of disease (group B; n = 3) after HSCT. Immune reconstitution was analyzed every 3 months using lymphocyte immunophenotyping, alpha/beta T cell receptor (TCR) diversity analysis, and ex vivo thymic function analysis by quantification of TCR rearrangement excision circles (TRECs).
Patients had similar characteristics at study entry, except for a lower modified Rodnan skin thickness score (P = 0.03) and a lower Health Assessment Questionnaire score (P = 0.05) in group A than in group B. The number of reinjected cells and the time to hematopoietic reconstitution were similar in both groups. The absolute numbers of CD19+ and CD20+ B cells were lower in group A than in normal controls (P < 0.05) and within the normal range in group B. Absolute numbers of T and natural killer lymphocytes were normal before HSCT. Numbers of CD3+ cells remained low thereafter. Numbers of CD8+ cells were back to normal 3 months after HSCT in both groups. B cell counts were low until 6 months after HSCT in group A and stayed in the normal range in group B. The CD3+ defect was sustained in group A, with an opposite trend and a faster CD4+ reconstitution profile in group B. The T cell repertoire was skewed before and until 1 year after HSCT, with shared expansions before and after transplant in a given individual. TREC values correlated negatively with C-reactive protein levels (r(s) = -0.41, P = 0.001) and positively with CD19+ (r(s) = 0.35, P = 0.001) and CD20+ (r(s) = 0.34, P = 0.002) lymphocyte counts.
B and T lymphocyte populations remained disturbed for at least 1 year after HSCT in SSc patients, which may reflect the persistence of an underlying disease mechanism.
分析7例系统性硬化症（SSc）患者自体造血干细胞移植（HSCT）后的造血和免疫重建情况。
根据HSCT后临床反应良好（A组；n = 4）或无反应或疾病复发（B组；n = 3），回顾性地将患者分为两组。每3个月使用淋巴细胞免疫表型分析、α/β T细胞受体（TCR）多样性分析以及通过定量TCR重排切除环（TREC）进行体外胸腺功能分析来分析免疫重建情况。
研究开始时患者具有相似的特征，但A组的改良Rodnan皮肤厚度评分较低（P = 0.03），健康评估问卷评分较低（P = 0.05），均低于B组。两组重新注入细胞的数量和造血重建时间相似。A组CD19 +和CD20 + B细胞的绝对数量低于正常对照组（P < 0.05），而B组在正常范围内。HSCT前T淋巴细胞和自然杀伤淋巴细胞的绝对数量正常。此后CD3 +细胞数量持续较低。两组HSCT后3个月CD8 +细胞数量恢复正常。A组B细胞计数在HSCT后6个月内一直较低，而B组保持在正常范围内。A组CD3 +缺陷持续存在，B组则呈现相反趋势且CD4 +重建速度更快。HSCT前及术后1年内T细胞库均存在偏态，特定个体移植前后有共同的扩增。TREC值与C反应蛋白水平呈负相关（r(s) = -0.41，P = 0.001），与CD19 +（r(s) = 0.35，P = 0.001）和CD20 +（r(s) = 0.34，P = 0.002）淋巴细胞计数呈正相关。
SSc患者HSCT后B和T淋巴细胞群体至少1年内仍处于紊乱状态，这可能反映了潜在疾病机制的持续存在。
