Department of Hematology, Tianjin Medical University General Hospital, Tianjin, China.
Department of Hematology, The First People's Hospital of Changde City, Changde, China.
J Clin Lab Anal. 2022 Oct;36(10):e24677. doi: 10.1002/jcla.24677. Epub 2022 Sep 9.
Clinically, to make a definite diagnosis of aplastic anemia (AA), idiopathic cytopenia of undetermined significance (ICUS) or myelodysplastic syndrome (MDS), they should be distinguished from each other. AA and ICUS have some incidence to transform into MDS. Immunosuppressive therapy (IST) is effective in AA and partial ICUS patients, while other ICUSs are more likely to progress to MDS without response to IST. To date, we neither found a technical method that could easily identify AA from hypoproliferative MDS, nor a simple parameter that could indicate ICUS with a response to IST. Here, we detected the concentration of free immune checkpoints in bone marrow supernatant of AA, ICUS, and MDS patients, analyzed the differences of immune status among these three diseases, to try to find a way to predict the response to IST in ICUSs.
Seventy-four novel patients were enrolled with newly diagnosed acquired bone marrow failure (including 29 AA patients, 11 ICUS patients, and 34 MDS patients), bone marrow supernatants were collected. Luminex liquid suspension array technology was used to measure the concentrations of 17 immune checkpoints to analyze the differences of immune status among these three diseases.
The levels of 17 free immune checkpoints were elevated in MDS and showed a strong correlation with each other, followed by ICUS, and with the weakest in AA. By drawing the ROC curve, we found eight immune checkpoints, including sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2, could easily distinguish AA from hypoproliferative MDS. ICUSs with lower concentrations of these eight free immune checkpoints predicted a better IST response.
In conclusion, we found that there were notable differences in the immune status of AA, ICUS, and MDS. The concentrations of sCD40, sCD86/B7-2, sCTLA-4, sGITR, sHVEM, sPD-1, sTIM-3, and sTLR-2 could be used to identify AA and hypoproliferative MDS patients, as well as to distinguish ICUS patients who could benefit from IST.
临床上，为了明确再生障碍性贫血（AA）、特发性细胞减少症的意义不明（ICUS）或骨髓增生异常综合征（MDS）的诊断，需要将它们彼此区分开来。AA 和 ICUS 都有一定的发病率转变为 MDS。免疫抑制治疗（IST）对 AA 和部分 ICUS 患者有效，而其他 ICUS 则更有可能进展为 MDS，而对 IST 无反应。迄今为止，我们既没有找到一种能够轻易将 AA 与低增生性 MDS 区分开来的技术方法，也没有找到一个简单的参数来表示对 IST 有反应的 ICUS。在这里，我们检测了 AA、ICUS 和 MDS 患者骨髓上清液中游离免疫检查点的浓度，分析了这三种疾病之间免疫状态的差异，试图找到一种预测 ICUS 对 IST 反应的方法。
共纳入 74 例新诊断的获得性骨髓衰竭患者（包括 29 例 AA 患者、11 例 ICUS 患者和 34 例 MDS 患者），收集骨髓上清液。采用 Luminex 液体悬浮芯片技术检测 17 种免疫检查点的浓度，分析三种疾病之间免疫状态的差异。
MDS 患者的 17 种游离免疫检查点水平升高，且彼此之间呈强相关，其次是 ICUS，AA 最弱。通过绘制 ROC 曲线，我们发现 8 种免疫检查点，包括 sCD40、sCD86/B7-2、sCTLA-4、sGITR、sHVEM、sPD-1、sTIM-3 和 sTLR-2，可轻易区分 AA 与低增生性 MDS。这些 8 种游离免疫检查点浓度较低的 ICUS 患者预测 IST 反应更好。
总之，我们发现 AA、ICUS 和 MDS 的免疫状态存在显著差异。sCD40、sCD86/B7-2、sCTLA-4、sGITR、sHVEM、sPD-1、sTIM-3 和 sTLR-2 的浓度可用于识别 AA 和低增生性 MDS 患者，并区分可能受益于 IST 的 ICUS 患者。
