Escape hematopoiesis by HLA-B5401-lacking hematopoietic stem progenitor cells in men with acquired aplastic anemia

El-Badry, Mahmoud; Mizumaki, Hiroki; Hosokawa, Kohei; Espinoza, J. Luis; Nakagawa, Noboru; Chonabayashi, Kazuhisa; Yoshida, Yoshinori; Katagiri, Takamasa; Hosomichi, Kazuyoshi; Zaimoku, Yoshitaka; Imi, Tatsuya; Nguyễn, Mai Ánh; Fujii, Youichi; Tajima, Atsushi; Ogawa, Seishi; Takenaka, Katsuto; Akashi, Koichi; Nakao, Shinji

doi:10.3324/haematol.2018.210856

Cited by 10 publications

(8 citation statements)

References 13 publications

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“…The importance of non-hematopoietic cells is highlighted by the recent finding showing that bone marrow mesenchymal stem cells can regulate Treg/Th17 balance in IAA [13]. Somatic gene and chromosome aberrations leading to the loss of one HLA I haplotype [14][15][16][17][18][19] are additional factors modulating the HSCs susceptibility to immune attack, likely by reducing recognition and attack by autoreactive T cells [16,20].…”

Section: Introductionmentioning

confidence: 99%

Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia

et al. 2022

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In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclooxygenase 2 (COX-2, aCOX-2 Ab). In total, 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the >40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable disease biomarker.

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Section: Introductionmentioning

confidence: 99%

Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia

et al. 2022

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“…Babushok et al identified mutations in several HLA class I alleles in leukocytes of AA patients, including HLA-A*33:03, A*68:01 and HLA-B*14:02 (14). We recently analyzed leukocytes of AA patients with 6pLOH and detected somatic loss-of-function mutations in HLA-A*02:06 and B*54:01 (16,17). However, HLA class I alleles responsible for autoantigen presentation in AA patients without HLA-B*40:02, who account for approximately 80% of the total AA patients, are largely unknown due to the limited number of AA patients that have been studied for loss-of-function mutations in HLA class I alleles.…”

Section: Introductionmentioning

confidence: 99%

A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia

et al. 2020

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“…Induced pluripotent stem cell (iPSC) clones with different phenotypes from cases 1 and 8 were cultured and differentiated into HSPCs using the previously described method (13,14). The HLA expression of each clone in case 1 was as follows: the WT clone (A02:01/A24:02, B35:01/B40:02, C08:01/C03:04), the B*40: 02 mut (B61 2 ) clone (A02:01/A24:02, B35:01/-, C08:01/C03:04), and the 6pLOH clone (A02:01/A02:01, B35:01/B35:01, C08:01/C08: 01) (14).…”

Section: Differentiation Of Hspcs From Induced Pluripotent Stem Cellsmentioning

confidence: 99%

“…As case 8's BM cells were unavailable for the examination of HLA-F, the iPSC-derived CD34 + cells were collected from three different iPSCs, including WT, HLA-B*54:01-mutated, and 6pLOH(+) iPSCs from case 8, which had been established in our previous study (13). The iPSC-derived CD34 + cells showed different phenotypes (A24 -Bw6 -[6pLOH], A24 + Bw6 -, and A24 + Bw6 + [WT]) compatible with HLA genotypes of each iPSC clone (Fig.…”

Section: The Expression Of Hla-f By Ipsc-derived Hscs With or Withoutmentioning

confidence: 99%

Resistance of KIR Ligand–Missing Leukocytes to NK Cells In Vivo in Patients with Acquired Aplastic Anemia

et al. 2020

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The loss of killer cell Ig-like receptor ligands (KIR-Ls) due to the copy number-neutral loss of heterozygosity of chromosome 6p (6pLOH) in leukocytes of patients with acquired aplastic anemia (AA) may alter the susceptibility of the affected leukocytes to NK cell killing in vivo. We studied 408 AA patients, including 261 who were heterozygous for KIR-Ls, namely C1/C2 or Bw6/Bw4, for the presence of KIR-L-missing [KIR-L(2)] leukocytes. KIR-L(2) leukocytes were found in 14 (5.4%, C1 [n = 4], C2 [n = 3], and Bw4 [n = 7]) of the 261 patients, in whom corresponding KIR(+) licensed NK cells were detected. The incidence of 6pLOH in the 261 patients (18.0%) was comparable to that in 147 patients (13.6%) who were homozygous for KIR-L genes. The percentages of HLA-lacking granulocytes (0.8-50.3%, median 15.2%) in the total granulocytes of the patients with KIR-L(2) cells were significantly lower than those (1.2-99.4%, median 55.4%) in patients without KIR-L(2) cells. KIR2DS1 and KIR3DS1 were only possessed by three of the 14 patients, two of whom had C2/C2 leukocytes after losing C1 alleles. The expression of the KIR3DS1 ligand HLA-F was selectively lost on KIR-L(2) primitive hematopoietic stem cells derived from 6pLOH(+) induced pluripotent stem cells in one of the KIR3DS1(+) patients. These findings suggest that human NK cells are able to suppress the expansion of KIR-L(2) leukocytes but are unable to

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Escape hematopoiesis by HLA-B5401-lacking hematopoietic stem progenitor cells in men with acquired aplastic anemia

Cited by 10 publications

References 13 publications

Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia

Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia

A frequent nonsense mutation in exon 1 across certain HLA-A and -B alleles in leukocytes of patients with acquired aplastic anemia

Resistance of KIR Ligand–Missing Leukocytes to NK Cells In Vivo in Patients with Acquired Aplastic Anemia

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