The Genetic Polymorphisms of NLRP3 Inflammasome Associated with T Helper Cells in Patients with Multiple Myeloma

Abstract

The pathogenesis of multiple myeloma (MM) remains unclear and the NLRP3 inflammasome has been more and more recognized in the progression of many diseases. To investigate the role of the NLRP3 inflammasome in MM, we determined the genetic polymorphisms and expression of NLRP3 inflammasome-related genes (IL-1β, IL-18, CARD8, and NF-κB) in MM patients, and explored their clinical relevance. Furthermore, we investigated the relationship of the NLRP3 inflammasome with Th cells in MM. Our study showed that the CARD8-C10X (rs2043211) AT genotype contributed to the susceptibility of MM. CARD8-C10X TT patients had earlier clinical stage. The WBC count in the three CARD8 genotypes showed an increasing trend (AA<AT<TT). Compared with patients with NF-κB-94 ins/del ATTG ins/ins and ins/del, patients with del/del had the highest myeloma cell ratio. Patients with IL-18 (rs16944) TT had the highest hemoglobin concentration (GG<GT<TT). Furthermore, we found that the genotype of CARD8-C10X (rs2043211) or NF-κB-94 ins/del ATTG was closely related to the frequency of Th1. Therefore, the genetic polymorphisms of the NLRP3 inflammasome associated with Th cells might be involved in the pathogenesis of multiple myeloma.

Standardization of sampling and sample preparation for analysis of human monocyte subsets in peripheral blood

“…A recent study described a possible role of the NLRP3 inflammasome and its downstream cytokines in the development of myeloma [325]; such a role in myeloma pathogenesis for the cytokine network and immunocompetent cells has also been suggested by immunogenetic studies [326]. These observations further suggest that immunocompetent cells, immunogenetic factors, or both are involved in the pathogenesis of multiple myeloma.…”

The Inflammasome Adaptor ASC Intrinsically Limits CD4+ T-Cell Proliferation to Help Maintain Intestinal Homeostasis

“…Some other studies more broadly have implicated the NLRP3 inflammasome in cancer and links to proliferation of T cells/lymphoma cells. In multiple myeloma patients with a mutation in CARD8 (a negative regulator of NLRP3 inflammasome) had a significantly higher percentage of pro-inflammatory Th1 cells (37). Another study from the same group has shown that NLRP3 inflammasome activation promoted lymphoma cells proliferation and inhibited apoptosis through up-regulation of c-myc and bcl-2 anti-apoptotic factors (38).…”

NLRP3 Inflammasome Promotes the Progression of Acute Myeloid Leukemia via IL-1β Pathway

“…Therefore, antagonists, such as small molecules or antibodies targeting components of the inflammasome complex are developed (9,27). Our previous studies also demonstrated that the polymorphisms of NLRP3 inflammasome might be involved in the pathogenesis of hematological malignancies, such as lymphoma (28), multiple myeloma (29), myelodysplastic syndromes (30) and AML (31). Moreover, we found that aberrant NLRP3 expression associated with Aryl hydrocarbon receptor (AHR) may contribute to Th cells imbalance in AML patients (3).…”