HLA associations, somatic loss of HLA expression, and clinical outcomes in immune aplastic anemia.

Autor: Zaimoku Y; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Patel BA; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Adams SD; Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD; and., Shalhoub R; Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Groarke EM; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Lee AAC; Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD; and., Kajigaya S; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Feng X; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Rios OJ; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Eager H; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Alemu L; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Quinones Raffo D; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Wu CO; Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD., Flegel WA; Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD; and., Young NS; Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
Jazyk: angličtina
Zdroj: Blood [Blood] 2021 Dec 30; Vol. 138 (26), pp. 2799-2809.
DOI: 10.1182/blood.2021012895
Abstrakt: Immune aplastic anemia (AA) features somatic loss of HLA class I allele expression on bone marrow cells, consistent with a mechanism of escape from T-cell-mediated destruction of hematopoietic stem and progenitor cells. The clinical significance of HLA abnormalities has not been well characterized. We examined the somatic loss of HLA class I alleles and correlated HLA loss and mutation-associated HLA genotypes with clinical presentation and outcomes after immunosuppressive therapy in 544 AA patients. HLA class I allele loss was detected in 92 (22%) of the 412 patients tested, in whom there were 393 somatic HLA gene mutations and 40 instances of loss of heterozygosity. Most frequently affected was HLA-B*14:02, followed by HLA-A*02:01, HLA-B*40:02, HLA-B*08:01, and HLA-B*07:02. HLA-B*14:02, HLA-B*40:02, and HLA-B*07:02 were also overrepresented in AA. High-risk clonal evolution was correlated with HLA loss, HLA-B*14:02 genotype, and older age, which yielded a valid prediction model. In 2 patients, we traced monosomy 7 clonal evolution from preexisting clones harboring somatic mutations in HLA-A*02:01 and HLA-B*40:02. Loss of HLA-B*40:02 correlated with higher blood counts. HLA-B*07:02 and HLA-B*40:01 genotypes and their loss correlated with late-onset of AA. Our results suggest the presence of specific immune mechanisms of molecular pathogenesis with clinical implications. HLA genotyping and screening for HLA loss may be of value in the management of immune AA. This study was registered at clinicaltrials.gov as NCT00001964, NCT00061360, NCT00195624, NCT00260689, NCT00944749, NCT01193283, and NCT01623167.
(© 2021 by The American Society of Hematology.)
Databáze: MEDLINE
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