Clinical significance of HLA-E genotype and surface/soluble expression levels between healthy individuals and patients with acute leukemia

Xu, Yunping; Wieten, Lotte; Wang, Song-Xing; Cai, Yun; Olieslagers, Timo I.; Zhang, Li; He, Liumei; Tilanus, M.G.J.; Hong, Wenxu

doi:10.1080/10428194.2018.1474521

Cited by 15 publications

(7 citation statements)

References 28 publications

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“…Women carrying the HLA-E G allele are more susceptible to serous ovarian cancer [72]. HLA-E G homozygous genotype is associated with significantly higher risk of acute leukemia and higher level of sHLA-E in the patient group [73]. Among nasopharyngeal carcinoma patients, HLA-E G allele was significantly more frequent than HLA-E R [74].…”

Section: Hla-e Dimorphism and Cancermentioning

confidence: 99%

“…Hirankarn with colleagues suggested that HLA-E R could be beneficial for antitumor immune responses due to lower surface expression of HLA-E*01:01, which results in lower inhibitory action for CD94 + /NKG2A + immune cells [74]. Also, two reports indicated the association between HLA-E G and the level of sHLA-E in patients’ sera [59,73]. As discussed earlier, sHLA-E provides the protection of cells from NK-mediated lysis.…”

Section: Hla-e Dimorphism and Cancermentioning

confidence: 99%

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Dimorphism of HLA-E and Its Disease Association

Kanevskiy

Erokhina

Kobyzeva

et al. 2019

IJMS

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HLA-E is a nonclassical member of the major histocompatibility complex class I gene locus. HLA-E protein shares a high level of homology with MHC Ia classical proteins: it has similar tertiary structure, associates with β2-microglobulin, and is able to present peptides to cytotoxic lymphocytes. The main function of HLA-E under normal conditions is to present peptides derived from the leader sequences of classical HLA class I proteins, thus serving for monitoring of expression of these molecules performed by cytotoxic lymphocytes. However, opposite to multiallelic classical MHC I genes, HLA-E in fact has only two alleles—HLA-E*01:01 and HLA-E*01:03—which differ by one nonsynonymous amino acid substitution at position 107, resulting in an arginine in HLA-E*01:01 (HLA-ER) and glycine in HLA-E*01:03 (HLA-EG). In contrast to HLA-ER, HLA-EG has higher affinity to peptide, higher surface expression, and higher thermal stability of the corresponding protein, and it is more ancient than HLA-ER, though both alleles are presented in human populations in nearly equal frequencies. In the current review, we aimed to uncover the reason of the expansion of the younger allele, HLA-ER, by analysis of associations of both HLA-E alleles with a number of diseases, including viral and bacterial infections, cancer, and autoimmune disorders.

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Section: Hla-e Dimorphism and Cancermentioning

confidence: 99%

Section: Hla-e Dimorphism and Cancermentioning

confidence: 99%

Dimorphism of HLA-E and Its Disease Association

Kanevskiy

Erokhina

Kobyzeva

et al. 2019

IJMS

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“…The Japanese encephalitis virus, a flavivirus responsible for encephalitis in Asian children, upregulates HLA-E cell-surface levels, coupled to an enhanced release of sHLA-E, suggesting a potential immuno-evasive strategy likely developed by the viral agent against host mediated immune responses 27 . In cancer, whilst high sHLA-E levels associate with a better overall survival in neuroblastoma 28 , high sHLA-E levels were also observed: (i) in advanced stages of chronic lymphocytic leukemia, with sHLA-E levels decreasing after treatment 29 ; and (ii) in patients suffering from acute leukemia, as compared to healthy controls 30 . Finally, in melanoma, several studies show high sHLA-E levels to be released by neo-transformed melanocytes 31 , a finding at the origin of the recent development of a novel immune check point inhibitor targeting the HLA-E specific NKG2A inhibitory receptor, namely Monalizumab 32 .…”

Section: Discussionmentioning

confidence: 99%

HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

Boukouaci

Lajnef

Richard

et al. 2021

Sci Rep

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Schizophrenia (SZ) and bipolar disorders (BD) are severe mental illnesses that lack reliable biomarkers to guide diagnosis and management. As immune dysregulation is associated with these disorders, we utilized the immunoregulatory functions of the natural killer cell inhibitory HLA-E locus to investigate the relationships between HLA-E genetic and expression diversities with SZ and BD risk and severity. Four hundred and forty-four patients meeting DSM-IV criteria for SZ (N = 161) or BD (N = 283) were compared to 160 heathy controls (HC). Circulating levels of the soluble isoform of HLA-E molecules (sHLA-E) were measured and HLA-E*01:01 and HLA-E*01:03 variants genotyped in the whole sample. sHLA-E circulating levels were significantly higher in both SZ and in BD patients compared to HC (pc < 0.0001 and pc = 0.0007 for SZ and BD, respectively). High sHLA-E levels were also observed in stable SZ patients and in acute BD patients experiencing depressive episodes when comparisons were made between the acute and stable subgroups of each disorder. sHLA-E levels linearly increased along HLA-E genotypes (p = 0.0036). In conclusion, HLA-E variants and level may have utility as diagnostic biomarkers of SZ and BD. The possible roles of HLA diversity in SZ and BD etiology and pathophysiology are discussed.

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“…In addition to HLA-G, HLA-E expression can be observed in multiple cancer entities such as breast cancer [132], colorectal cancer [158,159,160,201], renal cancer [173,202,203], lung cancer [204], melanoma [205,206], and gastric cancer [207,208], cervical cancer (adenocarcinoma) [209], glioblastoma [174,177,210], Hepatic carcinoma (hepatocellular) [211], Hodgkin’s lymphoma [212], Thyroid cancer [213] and leukemia [214]. Table 3 shows an overview of tumors in which expression of HLA-E has been detected.…”

Section: “Embryonic“ Hla Genes In Tumorsmentioning

confidence: 99%

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

Würfel¹,

Winterhalter²,

Trenkwalder³

et al. 2019

IJMS

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The granted European patent EP 2 561 890 describes a procedure for an immunological treatment of cancer. It is based on the principles of the HLA-supported communication of implantation and pregnancy. These principles ensure that the embryo is not rejected by the mother. In pregnancy, the placenta, more specifically the trophoblast, creates an “interface” between the embryo/fetus and the maternal immune system. Trophoblasts do not express the “original” HLA identification of the embryo/fetus (HLA-A to -DQ), but instead show the non-classical HLA groups E, F, and G. During interaction with specific receptors of NK cells (e.g., killer-immunoglobulin-like receptors (KIR)) and lymphocytes (lymphocyte-immunoglobulin-like receptors (LIL-R)), the non-classical HLA groups inhibit these immunocompetent cells outside pregnancy. However, tumors are known to be able to express these non-classical HLA groups and thus make use of an immuno-communication as in pregnancies. If this occurs, the prognosis usually worsens. This patent describes, in a first step, the profiling of the non-classical HLA groups in primary tumor tissue as well as metastases and recurrent tumors. The second step comprises tailored antibody therapies, which is the subject of this patent. In this review, we analyze the underlying mechanisms and describe the currently known differences between HLA-supported communication of implantation and that of tumors.

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Clinical significance of HLA-E genotype and surface/soluble expression levels between healthy individuals and patients with acute leukemia

Cited by 15 publications

References 28 publications

Dimorphism of HLA-E and Its Disease Association

Dimorphism of HLA-E and Its Disease Association

HLA-E circulating and genetic determinants in schizophrenia and bipolar disorder

European Patent in Immunoncology: From Immunological Principles of Implantation to Cancer Treatment

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