Detection of 6pLOH in an aplastic anemia patient by in phase HLA genotyping

Kikkawa, Eri; Shiina, Takashi; Shigenari, Atsuko; Ozaki, Yuki; Suzuki, Shingo; Ando, Kiyoshi; Onizuka, Makoto

doi:10.1111/tan.13807

Cited by 6 publications

(6 citation statements)

References 21 publications

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“…This result indicated that most of the neutrophil precursor cells stimulated by G‐CSF had already developed LOH at the site of HLA damage. The SS‐SBT method is a simple next‐generation sequencing (NGS) method that can completely cover HLA alleles 12 …”

Section: Autoimmune Blood Diseasesmentioning

confidence: 99%

“…The SS-SBT method is a simple next-generation sequencing (NGS) method that can completely cover HLA alleles. 12 In addition, recent studies on fetal and neonatal alloimmune thrombocytopenia (FNAIT) have shown that the HLA molecule encoded by HLA-DRA/DRB3*01:01 is very important in this immune response. 13 This disease is caused by alloantibodies against human platelet antigen 1a (HPA-1a).…”

Section: Autoimmune Blood Diseasesmentioning

confidence: 99%

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Current research status of HLA in immune‐related diseases

Liu

Shao

2021

Immunity Inflam & Disease

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Human leukocyte antigen (HLA), also known as human major histocompatibility complex (MHC), is encoded by the HLA gene complex, and is currently known to have the highest gene density and the most polymorphisms among human chromosomal areas. HLA is divided into class I antigens, class II antigens, and class III antigens according to distribution and function. Classical HLA class I antigens include HLA‐A, HLA‐B, and HLA‐C; HLA class II antigens include HLA‐DP, HLA‐DQ, and HLA‐DR; nonclassical HLA class I and II molecules include HLA‐F, E, H, X, DN, DO, and DM; and others, such as complement, are class III antigens. HLA is closely related to the body's immune response, regulation, and surveillance and is of great significance in the study of autoimmune diseases, tumor immunity, organ transplantation, and reproductive immunity. HLA is an important research topic that bridges immunology and clinical diseases. With the development of research methods and technologies, there will be more discoveries and broader prospects.

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Section: Autoimmune Blood Diseasesmentioning

confidence: 99%

Section: Autoimmune Blood Diseasesmentioning

confidence: 99%

Current research status of HLA in immune‐related diseases

Liu

Shao

2021

Immunity Inflam & Disease

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“…Another method, employing NGS and termed "super high-resolution singlemolecule sequence-based typing," has recently been shown to detect HLA-LOH. 21 HLA-LOH is a well-documented phenomenon. It is relatively common in solid tumors, with estimates in various tumor types of 13%-50%.…”

Section: Discussionmentioning

confidence: 99%

Loss of heterozygosity leading to incorrect HLA typing for platelet‐transfusion refractory patient

et al. 2022

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Background Management of platelet‐transfusion refractory (PR) patients due to anti‐HLA antibodies includes the provision of HLA‐matched (HLAm) platelets (PLT) or PLTs that are negative for HLA antigens corresponding to the recipient antibodies. Obtaining HLAm PLTs is predicated on accurate HLA antigen typing of the recipient and donor. Here, we present the clinical implications of a case involving loss of heterozygosity (LOH) in a patient presented for PR workup. Study Design and Methods HLA typing was performed by three methods: (1) Real‐time PCR; (2) Sequence‐specific oligonucleotide (SSO) typing test; and (3) Next‐Generation Sequencing (NGS). Cytogenomic SNP microarray was utilized to assess LOH. Results A 30‐year‐old female with newly diagnosed acute myelogenous leukemia was found to be PR secondary to HLA sensitization. A peripheral blood (PB) sample, containing 93% myeloid blast cells, was sent for HLA typing for the provision of HLAm PLTs. HLA typing revealed homozygosity at the HLA‐A locus but was heterozygous at the ‐B and ‐C loci. After chemotherapy, HLA typing on a new PB sample, devoid of blast cells, identified HLA‐A locus heterozygosity, which was subsequently confirmed by real‐time PCR and NGS. Cytogenomic SNP microarray analysis demonstrated LOH of the HLA‐A locus on chromosome 6p in the pretreatment sample but not in the posttreatment sample. Conclusion In hematologic patients with high tumor burden, HLA homozygosity should be viewed with suspicion for potential LOH. Therefore, HLA testing should be repeated, preferably with a non‐hematological source (e.g., buccal swab) or following successful reduction of the tumor burden.

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“…Specifically, in IAA a mechanistic involvement of HLA is supported by HLA allele predilection and the modes of immune escape via somatic reshuffles of HLA locus (e.g., loss or uniparental disomy of chromosome 6p or somatic mutations in class I alleles). 2,3,5,20,21,22,23,24 While external triggers seem essential, genetic disease susceptibility factors (e.g., immunogenetic polymorphisms) appear to be operative. Unlike in other autoimmune disorders, the enrichment of some class I alleles in IAA remains limited to ethnicity-restricted series, 2 whereas the impact of class II loci on disease susceptibility (e.g., DRB1*15:01) has been historically well documented in multiple populations.…”

Section: Introductionmentioning

confidence: 99%

The Immunogenetic Basis of Idiopathic Bone Marrow Failure Syndromes: A Paradox of Similarity and Self-Presentation

Pagliuca

Gurnari

Awada

et al. 2021

Preprint

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Idiopathic aplastic anemia (IAA) is a rare autoimmune bone marrow failure disorder initiated by a human leukocyte antigen (HLA)-restricted T-cell response to unknown antigens. Immunogenetic patterns associated with self-antigenic presentation remain unclear. Herein we analyzed the molecular landscape of HLA complexes and T-cell receptor (TCR) repertoires of a large cohort of IAA patients and controls. We show that antigen binding sites of class II HLA molecules in IAA are characterized by a high level of structural homology, only partially explained by specific risk allele profiles, implying reduced binding capabilities compared to controls. Few amino acids within the synapsis HLA-DRB1-antigen-TCR, are identified as strongly associated with IAA phenotype. Those structural patterns may affect TCR repertoires, promoting immunological cross-reactivity and autoimmunity. These findings inform on the immunogenetic risk associated with IAA and on general pathophysiological mechanisms potentially involved in autoimmunity.

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Detection of 6pLOH in an aplastic anemia patient by in phase HLA genotyping

Cited by 6 publications

References 21 publications

Current research status of HLA in immune‐related diseases

Current research status of HLA in immune‐related diseases

Loss of heterozygosity leading to incorrect HLA typing for platelet‐transfusion refractory patient

The Immunogenetic Basis of Idiopathic Bone Marrow Failure Syndromes: A Paradox of Similarity and Self-Presentation

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