Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27
Ankylosing spondylitis (AS) belongs to a group of diseases, called spondyloarthropathies (SpA), that are strongly associated with the genetic marker HLA-B27. AS is characterized by inflammation of joints and primarily affects the spine. Over 160 subtypes of HLA-B27 are known, owing to high polymorph...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.795053/full |
| _version_ | 1818752993223245824 |
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| author | Amit Kumar Thakur Manni Luthra-Guptasarma |
| author_facet | Amit Kumar Thakur Manni Luthra-Guptasarma |
| author_sort | Amit Kumar Thakur |
| collection | DOAJ |
| description | Ankylosing spondylitis (AS) belongs to a group of diseases, called spondyloarthropathies (SpA), that are strongly associated with the genetic marker HLA-B27. AS is characterized by inflammation of joints and primarily affects the spine. Over 160 subtypes of HLA-B27 are known, owing to high polymorphism. Some are strongly associated with disease (e.g., B*2704), whereas others are not (e.g., B*2709). Misfolding of HLA-B27 molecules [as dimers, or as high-molecular-weight (HMW) oligomers] is one of several hypotheses proposed to explain the link between HLA-B27 and AS. Our group has previously established the existence of HMW species of HLA-B27 in AS patients. Still, very little is known about the mechanisms underlying differences in pathogenic outcomes of different HLA-B27 subtypes. We conducted a proteomics-based evaluation of the differential disease association of HLA B*2704 and B*2709, using stable transfectants of genes encoding the two proteins. A clear difference was observed in protein clearance mechanisms: whereas unfolded protein response (UPR), autophagy, and aggresomes were involved in the degradation of B*2704, the endosome–lysosome machinery was primarily involved in B*2709 degradation. These differences offer insights into the differential disease association of B*2704 and B*2709. |
| first_indexed | 2024-12-18T05:00:17Z |
| format | Article |
| id | doaj.art-c3073c3aa59c4dd99f4c65b62ec560d5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-18T05:00:17Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c3073c3aa59c4dd99f4c65b62ec560d52022-12-21T21:20:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.795053795053Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27Amit Kumar ThakurManni Luthra-GuptasarmaAnkylosing spondylitis (AS) belongs to a group of diseases, called spondyloarthropathies (SpA), that are strongly associated with the genetic marker HLA-B27. AS is characterized by inflammation of joints and primarily affects the spine. Over 160 subtypes of HLA-B27 are known, owing to high polymorphism. Some are strongly associated with disease (e.g., B*2704), whereas others are not (e.g., B*2709). Misfolding of HLA-B27 molecules [as dimers, or as high-molecular-weight (HMW) oligomers] is one of several hypotheses proposed to explain the link between HLA-B27 and AS. Our group has previously established the existence of HMW species of HLA-B27 in AS patients. Still, very little is known about the mechanisms underlying differences in pathogenic outcomes of different HLA-B27 subtypes. We conducted a proteomics-based evaluation of the differential disease association of HLA B*2704 and B*2709, using stable transfectants of genes encoding the two proteins. A clear difference was observed in protein clearance mechanisms: whereas unfolded protein response (UPR), autophagy, and aggresomes were involved in the degradation of B*2704, the endosome–lysosome machinery was primarily involved in B*2709 degradation. These differences offer insights into the differential disease association of B*2704 and B*2709.https://www.frontiersin.org/articles/10.3389/fimmu.2021.795053/fullHLA-B27 alleleshigh molecular weight (HMW)aggregatesclearanceproteomics |
| spellingShingle | Amit Kumar Thakur Manni Luthra-Guptasarma Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 Frontiers in Immunology HLA-B27 alleles high molecular weight (HMW) aggregates clearance proteomics |
| title | Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 |
| title_full | Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 |
| title_fullStr | Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 |
| title_full_unstemmed | Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 |
| title_short | Differences in Cellular Clearing Mechanisms of Aggregates of Two Subtypes of HLA-B27 |
| title_sort | differences in cellular clearing mechanisms of aggregates of two subtypes of hla b27 |
| topic | HLA-B27 alleles high molecular weight (HMW) aggregates clearance proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.795053/full |
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