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F158V 等位基因频率在多发性骨髓瘤患者和健康人群中存在差异。

F158V alleles frequency differs in multiple myeloma patients from healthy population.

机构信息

IRMB, Univ Montpellier, INSERM, CHU Montpellier, Montpellier, France.

Department of Clinical Hematology, CHU Montpellier, Montpellier, France.

出版信息

Oncoimmunology. 2024 Aug 18;13(1):2388306. doi: 10.1080/2162402X.2024.2388306. eCollection 2024.

Abstract

presents a single nucleotide polymorphism at location 158 (V/F), which affects its binding to the fragment crystallizable (Fc) of antibodies (Abs). FcγRIIIa-158 V allotype has the highest affinity and is associated with a better clinical response to IgG1 monoclonal Abs (mAb) treatment. We compared the allele frequency of F158V polymorphism in cohorts of patients with B-cell lymphoproliferative disorders, including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), non-Hodgkin lymphoma (NHL), and B-cell chronic leukemia (B-CLL). -158F homozygous were enriched and tended to be in MM and MGUS patients, respectively; but neither in B-CLL nor in NHL patients. We identified a significantly lower concentration of CD8 T-cells and resting memory CD4 T-cells in MM patients bone marrow with the F/F genotype, associated with an increase in the macrophage percentage. In contrast, natural killer cells increased in V/V homozygous patients. This suggests a deregulation of the immune microenvironment in -F/F homozygous patients. However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.

摘要

该研究提出了一个位于 158 位的单核苷酸多态性(V/F),它影响了它与抗体(Abs)的片段结晶区(Fc)的结合。FcγRIIIa-158V 同种型具有最高的亲和力,并与 IgG1 单克隆抗体(mAb)治疗的更好临床反应相关。我们比较了 F 细胞系 158V 多态性在 B 细胞淋巴增生性疾病患者队列中的等位基因频率,包括多发性骨髓瘤(MM)、意义未明单克隆丙种球蛋白血症(MGUS)、非霍奇金淋巴瘤(NHL)和 B 细胞慢性淋巴细胞白血病(B-CLL)。-158F 纯合子在 MM 和 MGUS 患者中分别富集并趋于富集;但在 B-CLL 和 NHL 患者中均未富集。我们发现 MM 患者骨髓中 F/F 基因型的 CD8 T 细胞和静止记忆 CD4 T 细胞浓度显著降低,与巨噬细胞百分比增加相关。相比之下,V/V 纯合子患者的自然杀伤细胞增加。这表明 F/F 纯合子患者的免疫微环境失调。然而,我们没有观察到与 daratumumab(一种直接针对 CD38 的 IgG1 mAb)联合化疗或不联合化疗的治疗反应存在差异。我们的研究结果表明,F158V 多态性可以调节免疫环境,影响肿瘤浆细胞的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36fd/11340758/fe2c480e9c99/KONI_A_2388306_F0001_OC.jpg

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