Abstract
Objective To analyze and study the correlation between NLR family CARD domain-containing 4 (NLRC4) gene single nucleotide polymorphisms and the prognosis of patients with hemophagocytic lymphohistiocytosis (HLH). Methods In this study, we retrospectively studied the clinical data of 62 HLH patients, including 40 males and 22 females. The genomic DNA was extracted, and the genotypes at rs385076 locus and rs479333 locus of the NLRC4 gene were analyzed. The level of blood interleukin-18 (IL-18) was analyzed by enzyme-linked immunosorbent assay (ELISA). Results Compared with the TT genotype at the NLRC4 gene rs385076 locus, the mortality of HLH patients with TC genotype and CC genotype was higher (RR = 3.205, 95% CI: 1.277-4.788, p = 0.012; RR = 3.052, 95% CI: 1.098-4.753, p = 0.031). Taking the CC genotype at rs479333 of the NLRC4 gene as a reference, HLH patients with CG genotype and GG genotype had a higher risk of death (RR = 3.475, 95% CI: 1.488-5.775, p = 0.003; RR = 2.986, 95% CI: 1.014-5.570, p = 0.047). NLRC4 gene rs385076 T>C and rs479333 C>G were significantly related to the poor prognosis of HLH patients. The area under the curve (AUC) of the receiver operating curve (ROC) for the prognostic outcome of HLH with serum IL-18 level was 0.6813 (95% CI: 0.5365-0.8260, p = 0.0189). NLRC4 gene rs385076 T>C and rs479333 C>G were related to higher serum IL-18 levels. Conclusion NLRC4 gene rs385076 T>C and rs479333 C>G are related to the poor prognosis of HLH patients.
Highlights
Hemophagocytic syndrome, known as hemophagocytic lymphohistiocytosis (HLH), is due to the excessive activation and proliferation of macrophages, accompanied by decreased activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), granzyme-dependent cytotoxicity defect, which in turn induce a series of clinical syndromes caused by immune dysfunction [1,2,3].According to the different triggering factors of HLH, HLH includes primary HLH and secondary HLH
Recent studies have shown that the dysfunction of CTL, NK cells, and macrophages and the sharp increase in cytokine levels play an important role in the pathogenesis of HLH [4]
We explored the correlation between the single nucleotide polymorphisms of the NLR family CARD domain-containing 4 (NLRC4) gene and the prognosis of HLH patients, aiming to provide valuable markers for the prognosis of HLH patients
Summary
Hemophagocytic syndrome, known as hemophagocytic lymphohistiocytosis (HLH), is due to the excessive activation and proliferation of macrophages, accompanied by decreased activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), granzyme-dependent cytotoxicity defect, which in turn induce a series of clinical syndromes caused by immune dysfunction [1,2,3].According to the different triggering factors of HLH, HLH includes primary HLH and secondary HLH. Hemophagocytic syndrome, known as hemophagocytic lymphohistiocytosis (HLH), is due to the excessive activation and proliferation of macrophages, accompanied by decreased activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL), granzyme-dependent cytotoxicity defect, which in turn induce a series of clinical syndromes caused by immune dysfunction [1,2,3]. Recent studies have shown that the dysfunction of CTL, NK cells, and macrophages and the sharp increase in cytokine levels play an important role in the pathogenesis of HLH [4]. The continuous attention of research has led us to discover that more and more gene mutations are involved in the occurrence of HLH. The study of Yang et al [6] proved for the first time that the polymorphism of STXBP2 rs2303116 was related to the pathogenesis of HLH. The above gene mutations affect the synthesis, transportation, anchoring, initiation, or membrane fusion of cytotoxic particles, resulting in the inability of cytotoxic particles to be secreted outside the cell; as a result, the killing function of Computational and Mathematical Methods in Medicine
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