Ancestry-based differences in the immune system are associated with lupus severity Article Swipe
Samantha Slight‐Webb
,
Kevin Thomas
,
Miles Smith
,
Susan Macwana
,
Aleksandra Bylinska
,
Joseph Kheir
,
Michele Donato
,
Mai Dvorak
,
Sarah E. Chang
,
Alex Kuo
,
Peggie Cheung
,
Laurynas Kalesinskas
,
Ananthakrishnan Ganesan
,
Denis Đermadi
,
Carla J. Guthridge
,
Wade DeJager
,
Christian D. Wright
,
Bolanle Adebayo
,
Mariko H. Foecke
,
Joan T. Merrill
,
Eliza F. Chakravarty
,
Cristina Arriens
,
Holden T. Maecker
,
Purvesh Khatri
,
Paul J. Utz
,
Judith A. James
,
Joel M. Guthridge
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1149629/v1
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-1149629/v1
Systemic lupus erythematosus (SLE) affects 1 in 537 of African American (AA) women, which is >2-fold more than European American (EA) women. AA patients also develop the disease at a younger age, have more severe symptoms, and a greater chance of early mortality. We used a multi-omics approach to uncover ancestry-specific immune alterations in SLE patients and healthy controls that may contribute to disease disparities. Cell composition, signaling, and epigenetics were evaluated by mass cytometry; droplet-based single cell transcriptomics and paired proteogenomics (scRNA-Seq/scCITE-Seq). Soluble mediator levels were measured in plasma and stimulated whole blood. Toll-like receptor (TLRs) pathways are activated by vaccination and microbial infection, and are also key drivers of autoimmune disease. We observed enhanced TLR3/4/7/8/9-related gene expression in immune cells from AA versus EA SLE patients. TLR7/8/9 and IFNα phospho-signaling responses were heightened even in immune cells from healthy AA versus EA controls. TLR stimulation of healthy AA and EA immune cells recapitulated the distinct ancestry-associated SLE immunophenotypes. Thus, healthy individuals show ancestry-based differences in innate immune pathways that could influence the course and severity of lupus and other diseases.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-1149629/v1
- https://www.researchsquare.com/article/rs-1149629/latest.pdf
- OA Status
- gold
- Cited By
- 2
- References
- 44
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4200382799
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4200382799Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-1149629/v1Digital Object Identifier
- Title
-
Ancestry-based differences in the immune system are associated with lupus severityWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-12-29Full publication date if available
- Authors
-
Samantha Slight‐Webb, Kevin Thomas, Miles Smith, Susan Macwana, Aleksandra Bylinska, Joseph Kheir, Michele Donato, Mai Dvorak, Sarah E. Chang, Alex Kuo, Peggie Cheung, Laurynas Kalesinskas, Ananthakrishnan Ganesan, Denis Đermadi, Carla J. Guthridge, Wade DeJager, Christian D. Wright, Bolanle Adebayo, Mariko H. Foecke, Joan T. Merrill, Eliza F. Chakravarty, Cristina Arriens, Holden T. Maecker, Purvesh Khatri, Paul J. Utz, Judith A. James, Joel M. GuthridgeList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-1149629/v1Publisher landing page
- PDF URL
-
https://www.researchsquare.com/article/rs-1149629/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.researchsquare.com/article/rs-1149629/latest.pdfDirect OA link when available
- Concepts
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Systemic lupus erythematosus, Immune system, Immunology, Medicine, Internal medicine, DiseaseTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2022: 2Per-year citation counts (last 5 years)
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44Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.epigenetics | 70 |
| abstract_inverted_index.individuals | 163 |
| abstract_inverted_index.multi-omics | 47 |
| abstract_inverted_index.stimulation | 147 |
| abstract_inverted_index.vaccination | 102 |
| abstract_inverted_index.composition, | 67 |
| abstract_inverted_index.disparities. | 65 |
| abstract_inverted_index.droplet-based | 76 |
| abstract_inverted_index.erythematosus | 3 |
| abstract_inverted_index.recapitulated | 155 |
| abstract_inverted_index.ancestry-based | 165 |
| abstract_inverted_index.proteogenomics | 82 |
| abstract_inverted_index.transcriptomics | 79 |
| abstract_inverted_index.ancestry-specific | 51 |
| abstract_inverted_index.immunophenotypes. | 160 |
| abstract_inverted_index.phospho-signaling | 132 |
| abstract_inverted_index.ancestry-associated | 158 |
| abstract_inverted_index.TLR3/4/7/8/9-related | 117 |
| abstract_inverted_index.(scRNA-Seq/scCITE-Seq). | 83 |
| abstract_inverted_index.<title>Abstract</title> | 0 |
| cited_by_percentile_year.max | 96 |
| cited_by_percentile_year.min | 94 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 27 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8600000143051147 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.6355884 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |