Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Łódz, Poland.
Department of Hematology, Comprehensive Cancer Center and Traumatology, Copernicus Memorial Hospital, Łódz, Poland.
Front Immunol. 2020 Jan 28;10:3097. doi: 10.3389/fimmu.2019.03097. eCollection 2019.
A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between "self" "abnormal self," and "non-self" and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the corresponding (, and ) genes. Serum samples were collected before conditioning chemotherapy, before HSCT, and once weekly post-HSCT (four to five samples in total); some patients were also sampled at 1 and/or 3 months post-transplantation. The control group (C) consisted of 267 healthy unrelated individuals. Median ficolin-1 and ficolin-2 (but not ficolin-3) levels in MM patients' sera taken before chemotherapy were lower (and correspondingly frequencies of the lowest concentrations were higher) compared with controls. That appeared to be associated with the malignant disease itself rather than with post-HSCT complications (febrile neutropenia, infections accompanied, or not with bacteremia). Higher frequencies of the genotype G/A-C/C-G/G (corresponding to polymorphisms at positions -542, -144, and +6658, respectively) and gene heterozygosity for the -857 C>A polymorphism were found among patients diagnosed with MM compared with the C group. Furthermore, G/G homozygosity (-557 A>G) was found more frequently and heterozygosity G/T at +6424 less frequently among LYMPH patients than among the healthy subjects. Heterozygosity for +1637delC mutation of the gene was more common among patients diagnosed with lymphomas who experienced hospital infections. Although no evidence for an association of low ficolin-1 or ficolin-2 with infections during neutropenia following chemotherapy before HSCT was found, we observed a possible protective effect of ficolins during follow-up.
对 312 例接受高剂量化疗和自体造血干细胞移植(auto-HSCT)的患者[194 例多发性骨髓瘤(MM)和 118 例淋巴瘤(LYMPH)]进行了前瞻性研究。胶凝素是先天免疫防御因子,能够区分“自我”“异常自我”和“非自我”,通过直接调理作用和/或启动补体激活的凝集素途径有助于消除后两者。在连续采集的血清样本中测定胶凝素-1、胶凝素-2 和胶凝素-3 的浓度,并测定相应的(、和)基因的多态性。在预处理化疗前、HSCT 前和 HSCT 后每周一次(共采集四到五个样本)采集血清样本;一些患者还在移植后 1 个月和/或 3 个月时进行了采样。对照组(C)由 267 名健康无关个体组成。与对照组相比,化疗前 MM 患者血清中胶凝素-1 和胶凝素-2(而非胶凝素-3)水平较低(相应的最低浓度频率较高)。这似乎与恶性疾病本身有关,而与 HSCT 后并发症(发热性中性粒细胞减少症、伴有或不伴有菌血症的感染)无关。与 C 组相比,诊断为 MM 的患者中发现了更高频率的基因型 G/A-C/C-G/G(分别对应于-542、-144 和+6658 位的多态性)和-857 C>A 多态性的基因杂合性。此外,与健康受试者相比,LYMPH 患者中-557 A>G 的 G/G 纯合性和+6424 的 G/T 杂合性较少,而-6424 的 G/T 杂合性较少。诊断为淋巴瘤的患者中,发生医院感染的患者+1637delC 基因突变的基因杂合性更为常见。尽管在 HSCT 前化疗中性粒细胞减少期间没有发现低胶凝素-1 或胶凝素-2 与感染之间存在关联的证据,但我们观察到在随访期间胶凝素可能具有保护作用。