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Sarcopenia and Variation in the Human Leukocyte Antigen Complex.

ABSTRACT: BACKGROUND:Aging is characterized by chronic inflammation plus loss of muscle mass and strength, termed sarcopenia. Human leukocyte antigen (HLA) types are drivers of autoimmune disease, although with limited penetrance. We tested whether autoimmune diagnoses are associated with sarcopenia, and whether HLA types and related genetic variants are associated with sarcopenia in autoimmune disease-free older people. METHODS:Data were collected from 181,301 UK Biobank European descent volunteers aged 60-70 with measured hand grip strength and impedance. Logistic regression analysis estimated HLA type and sarcopenia associations, adjusted for confounders and multiple testing. RESULTS:Having any autoimmune diagnosis was associated with sarcopenia (odds ratio [OR] 1.83, 95% confidence interval (CI) 1.74-1.92, p = 4.0*10-125). After excluding autoimmune diagnoses, 6 of 100 HLA types (allele frequency >1%) were associated with sarcopenia (low grip strength and muscle mass). Having two HLA-DQA1*03:01 alleles increased odds of sarcopenia by 19.3% (OR 1.19, CI 1.09-1.29, p = 2.84*10-5), compared to no alleles. Having ?6 of the 12 HLA alleles increased sarcopenia odds by 23% (OR 1.23, CI 1.12-1.35, p = 7.28*10-6). Of 658 HLA region non-coding genetic variants previously implicated in disease, 4 were associated with sarcopenia, including rs41268896 and rs29268645 (OR 1.08, CI 1.05-1.11, p = 1.06*10-8 and 1.07, CI 1.04-1.09, p = 1.5*10-6, respectively). Some HLA associations with sarcopenia were greater in female participants. CONCLUSION:Autoimmune diagnoses are strongly associated with sarcopenia in 60- to 70-year olds. Variation in specific HLA types and non-coding single nucleotide polymorphisms is also associated with sarcopenia in older carriers free of diagnosed autoimmune diseases. Patients with sarcopenia might benefit from targeted treatment of autoimmune processes.

SUBMITTER: Jones G

PROVIDER: S-EPMC7176057 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Sarcopenia and Variation in the Human Leukocyte Antigen Complex.

Jones Garan G Pilling Luke C LC Kuo Chia-Ling CL Kuchel George G Ferrucci Luigi L Melzer David D

The journals of gerontology. Series A, Biological sciences and medical sciences 20200101 2

<h4>Background</h4>Aging is characterized by chronic inflammation plus loss of muscle mass and strength, termed sarcopenia. Human leukocyte antigen (HLA) types are drivers of autoimmune disease, although with limited penetrance. We tested whether autoimmune diagnoses are associated with sarcopenia, and whether HLA types and related genetic variants are associated with sarcopenia in autoimmune disease-free older people.<h4>Methods</h4>Data were collected from 181,301 UK Biobank European descent v ...[more]

PMID: 30772894

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Project description:Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor ?, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-? all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor ? were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

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Sarcopenia and Variation in the Human Leukocyte Antigen Complex.

Publications

Sarcopenia and Variation in the Human Leukocyte Antigen Complex.

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