Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

doi:10.1136/annrheumdis-2022-222345

. 2022 Aug 11;81(9):1273-1280.

doi: 10.1136/annrheumdis-2022-222345.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

Xianyong Yin^#^{1

2

3

4

5

6}, Kwangwoo Kim^#⁷, Hiroyuki Suetsugu^#^{8

9

10}, So-Young Bang^{11

12}, Leilei Wen^{1

2}, Masaru Koido^{9

13}, Eunji Ha⁷, Lu Liu^{1

2}, Yuma Sakamoto^{8

14}, Sungsin Jo¹², Rui-Xue Leng¹⁵, Nao Otomo^{8

9

16}, Young-Chang Kwon¹², Yujun Sheng^{1

2}, Nobuhiko Sugano¹⁷, Mi Yeong Hwang¹⁸, Weiran Li^{1

2}, Masaya Mukai¹⁹, Kyungheon Yoon¹⁸, Minglong Cai^{1

2}, Kazuyoshi Ishigaki^{9

20

21

22}, Won Tae Chung²³, He Huang^{1

2}, Daisuke Takahashi²⁴, Shin-Seok Lee²⁵, Mengwei Wang^{1

2}, Kohei Karino²⁶, Seung-Cheol Shim²⁷, Xiaodong Zheng^{1

2}, Tomoya Miyamura²⁸, Young Mo Kang²⁹, Dongqing Ye¹⁵, Junichi Nakamura³⁰, Chang-Hee Suh³¹, Yuanjia Tang³², Goro Motomura¹⁰, Yong-Beom Park³³, Huihua Ding³², Takeshi Kuroda³⁴, Jung-Yoon Choe³⁵, Chengxu Li⁴, Hiroaki Niiro³⁶, Youngho Park¹², Changbing Shen^{37

38}, Takeshi Miyamoto³⁹, Ga-Young Ahn¹¹, Wenmin Fei⁴, Tsutomu Takeuchi⁴⁰, Jung-Min Shin¹¹, Keke Li⁴, Yasushi Kawaguchi⁴¹, Yeon-Kyung Lee¹¹, Yong-Fei Wang⁴², Koichi Amano⁴³, Dae Jin Park¹¹, Wanling Yang⁴², Yoshifumi Tada⁴⁴, Yu Lung Lau⁴², Ken Yamaji⁴⁵, Zhengwei Zhu^{1

2}, Masato Shimizu⁴⁶, Takashi Atsumi⁴⁷, Akari Suzuki⁴⁸, Takayuki Sumida⁴⁹, Yukinori Okada^{50

51

52}, Koichi Matsuda^{53

54}, Keitaro Matsuo^{55

56}, Yuta Kochi⁵⁷; Japanese Research Committee on Idiopathic Osteonecrosis of the Femoral Head; Kazuhiko Yamamoto⁴⁸, Koichiro Ohmura⁵⁸, Tae-Hwan Kim^{11

12}, Sen Yang^{1

2}, Takuaki Yamamoto⁵⁹, Bong-Jo Kim¹⁸, Nan Shen^{32

60

61}, Shiro Ikegawa⁸, Hye-Soon Lee^{11

12}, Xuejun Zhang^{1

2

62}, Chikashi Terao^{63

64

65}, Yong Cui⁶⁶, Sang-Cheol Bae^{67

12}

Affiliations

¹ Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
² Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.
³ Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People's Republic of China.
⁴ Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.
⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
⁶ Human Phenome Institute, Fudan University, Shanghai, People's Republic of China.
⁷ Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
⁸ Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.
⁹ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁰ Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹¹ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
¹² Hanyang University Institute for Rheumatology Research, Seoul, South Korea.
¹³ Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁴ Koga Hospital 21, Kurume, Japan.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
¹⁶ Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
¹⁷ Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁸ Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea.
¹⁹ Department of Rheumatology & Clinical Immunology, Sapporo City General Hospital, Hokkaido, Japan.
²⁰ Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²¹ Center for Data Sciences, Harvard Medical School, Boston, MA, USA.
²² Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²³ Department of Internal Medicine, Dong-A University Hospital, Busan, South Korea.
²⁴ Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁵ Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, South Korea.
²⁶ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁷ Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea.
²⁸ Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
²⁹ Division of Rheumatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
³⁰ Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
³¹ Department of Rheumatology, Ajou University School of Medicine, Suwon, South Korea.
³² Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, People's Republic of China.
³³ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
³⁴ Niigata University Health Administration Center, Niigata, Japan.
³⁵ Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, South Korea.
³⁶ Department of Medical Education, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
³⁷ Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China.
³⁸ Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, People's Republic of China.
³⁹ Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴¹ Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
⁴² Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
⁴³ Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁴⁴ Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan.
⁴⁵ Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁶ Hokkaido Medical Center for Rheumatic Diseases, Sapporo, Japan.
⁴⁷ Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan.
⁴⁸ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁴⁹ Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁵⁰ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
⁵¹ Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
⁵² Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁵³ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁵⁴ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁵⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵⁷ Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵⁸ Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁵⁹ Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁶⁰ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China.
⁶¹ Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶² Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
⁶³ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁴ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
⁶⁵ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
⁶⁶ Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁷ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.

^# Contributed equally.

PMID: 35609976
PMCID: PMC9380500
DOI: 10.1136/annrheumdis-2022-222345

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

Xianyong Yin et al. Ann Rheum Dis. 2022.

. 2022 Aug 11;81(9):1273-1280.

doi: 10.1136/annrheumdis-2022-222345.

Authors

Affiliations

¹ Department of Dermatology and Institute of Dermatology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, People's Republic of China.
² Key Lab of Dermatology, Ministry of Education (Anhui Medical University), Hefei, Anhui, People's Republic of China.
³ Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui, People's Republic of China.
⁴ Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China.
⁵ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
⁶ Human Phenome Institute, Fudan University, Shanghai, People's Republic of China.
⁷ Department of Biology and Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Korea.
⁸ Laboratory for Bone and Joint Diseases, RIKEN Center for Medical Sciences, Tokyo, Japan.
⁹ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁰ Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
¹¹ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea.
¹² Hanyang University Institute for Rheumatology Research, Seoul, South Korea.
¹³ Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁴ Koga Hospital 21, Kurume, Japan.
¹⁵ Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People's Republic of China.
¹⁶ Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan.
¹⁷ Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
¹⁸ Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, South Korea.
¹⁹ Department of Rheumatology & Clinical Immunology, Sapporo City General Hospital, Hokkaido, Japan.
²⁰ Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²¹ Center for Data Sciences, Harvard Medical School, Boston, MA, USA.
²² Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
²³ Department of Internal Medicine, Dong-A University Hospital, Busan, South Korea.
²⁴ Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁵ Division of Rheumatology, Department of Internal Medicine, Chonnam National University Medical School and Hospital, Gwangju, South Korea.
²⁶ Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.
²⁷ Division of Rheumatology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea.
²⁸ Department of Internal Medicine and Rheumatology, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
²⁹ Division of Rheumatology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
³⁰ Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
³¹ Department of Rheumatology, Ajou University School of Medicine, Suwon, South Korea.
³² Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University, School of Medicine (SJTUSM), Shanghai, People's Republic of China.
³³ Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
³⁴ Niigata University Health Administration Center, Niigata, Japan.
³⁵ Department of Rheumatology, Catholic University of Daegu School of Medicine, Daegu, South Korea.
³⁶ Department of Medical Education, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
³⁷ Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China.
³⁸ Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, People's Republic of China.
³⁹ Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
⁴⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
⁴¹ Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
⁴² Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
⁴³ Department of Rheumatology & Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁴⁴ Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan.
⁴⁵ Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.
⁴⁶ Hokkaido Medical Center for Rheumatic Diseases, Sapporo, Japan.
⁴⁷ Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo, Japan.
⁴⁸ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁴⁹ Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
⁵⁰ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
⁵¹ Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
⁵² Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
⁵³ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁵⁴ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁵⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵⁷ Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
⁵⁸ Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁵⁹ Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁶⁰ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, People's Republic of China.
⁶¹ Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶² Department of Dermatology, Institute of Dermatology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
⁶³ Laboratory for Statistical and Translational Genetics Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁴ Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
⁶⁵ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
⁶⁶ Department of Dermatology, China-Japan Friendship Hospital, Beijing, People's Republic of China chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.
⁶⁷ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea chikashi.terao@riken.jp wuhucuiyong@vip.163.com scbae@hanyang.ac.kr.

^# Contributed equally.

PMID: 35609976
PMCID: PMC9380500
DOI: 10.1136/annrheumdis-2022-222345

Abstract

Objective: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis.

Methods: We built gene expression predictive models in blood B cells, CD4⁺ and CD8⁺ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches.

Results: TWAS identified 171 genes for SLE (p<1.0×10^-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10^-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10^-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression.

Conclusions: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Keywords: autoimmunity; lupus erythematosus, systemic; polymorphism, genetic.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1**
TWAS of East Asian meta-analysis data. (A) Distribution of significant genes across the six types of immune cells. (B) Number of significant TWAS genes per SLE locus. TWAS, transcriptome-wide association study.

**Figure 2**
Locuszoom plot for a new single-variant association at the *CD83* gene. Mb, megabase.

**Figure 3**
Venn diagram of candidate disease genes at the 110 SLE loci identified using four gene discovery approaches. DEPICT, Data-driven Expression-Prioritised Integration for Complex Traits; PoPS, Polygenic Priority Score; TWAS, transcriptome-wide association study.

**Figure 4**
Allele-specific regulatory effect of rs61759532 on *ACAP1*. (A) Regional association plot for the *ACAP1* locus. The lead variant rs61759532 is labelled as a purple diamond. Linkage disequilibrium was estimated using data from 7021 Chinese individuals. (B) Location of rs61759532 within an assay for transposase-accessible chromatin using sequencing open chromatin accessible region in CD19⁺ B and CD4⁺ T cells (green tracks) and within active ChromHMM chromatin states (bars on the bottom panel) in primary CD8⁺ T naive cells (CD8.NPC), T helper naive cells (CD4.NPC) and primary B cells (BLD.CD19.PPC). Chromatin states are coloured red (active transcription start site), orange red (flanking active transcription start site), or yellow (enhancers). (C) Allelic differential enhancing activity of rs61759532 in THP1 cells. None, 3×C, and 3×T denote an empty vector containing a minimal promoter, and vectors with the C and T alleles of rs61759532, respectively. Relative luciferase activities, measured in five independent biological replicates, were significantly higher for inserts with the C allele (two-tailed t-test p=8.1×10^–3). Error bars indicate SEMs of five independent biological replicates. (D) Association between the risk allele (T) of rs61759532 and decreased expression of *ACAP1* in GTEx v8 whole blood (p=1.7×10^–47). The white line in the centre of each box indicates the median expression value, while the box for each genotype represents the IQR of *ACACP1* expression. (E) Allelic differential protein-DNA binding by rs61759532 in EMSAs. Biotin-conjugated 30-nucleotide probes flanking rs61759532 (denoted as C or T, according to the allele) were incubated with nuclear extracts (10 µg) from EBV-transformed B cells or THP1 cells in EMSAs. Shifted bands (indicated by red arrows) had stronger intensities with the biotin-conjugated C allele probes than the T allele probes and were not detected in the presence of excess non-conjugated probes. EBV: Epstein-Barr Virus; EMSA, electrophoretic mobility shift assay; Mb, megabase; THP1: human leukemia monocytic cell line.

See this image and copyright information in PMC

Cited by

Thioredoxin is a metabolic rheostat controlling regulatory B cells.
Bradford HF, McDonnell TCR, Stewart A, Skelton A, Ng J, Baig Z, Fraternali F, Dunn-Walters D, Isenberg DA, Khan AR, Mauro C, Mauri C. Bradford HF, et al. Nat Immunol. 2024 May;25(5):873-885. doi: 10.1038/s41590-024-01798-w. Epub 2024 Mar 29. Nat Immunol. 2024. PMID: 38553615 Free PMC article.
Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus.
Tsai YG, Liao PF, Hsiao KH, Wu HM, Lin CY, Yang KD. Tsai YG, et al. Front Immunol. 2023 Sep 12;14:1230264. doi: 10.3389/fimmu.2023.1230264. eCollection 2023. Front Immunol. 2023. PMID: 37771588 Free PMC article. Review.
Investigating Overlapping Genetic Factors and Novel Causal Genes in Autoimmune Diseases: A Transcriptome-Wide Association and Multiomics Study.
Fu L, Yu J, Wang X, Chen Z, Sun J, Gao F, Zhang Z, Fu J, Hong P, Feng W. Fu L, et al. Int J Genomics. 2025 Jun 24;2025:9595651. doi: 10.1155/ijog/9595651. eCollection 2025. Int J Genomics. 2025. PMID: 40599891 Free PMC article.
The impact of chronic pain on brain gene expression.
Collier L, Seah C, Hicks EM; Traumatic Stress Brain Research Group; Holtzheimer PE, Krystal JH, Girgenti MJ, Huckins LM, Johnston KJA. Collier L, et al. medRxiv [Preprint]. 2024 May 21:2024.05.20.24307630. doi: 10.1101/2024.05.20.24307630. medRxiv. 2024. Update in: Pain. 2025 Jul 7. doi: 10.1097/j.pain.0000000000003707. PMID: 38826319 Free PMC article. Updated. Preprint.
Differential regulation of the interferon response in systemic lupus erythematosus distinguishes patients of Asian ancestry.
Rector I, Owen KA, Bachali P, Hubbard E, Yazdany J, Dall'era M, Grammer AC, Lipsky PE. Rector I, et al. RMD Open. 2023 Sep;9(3):e003475. doi: 10.1136/rmdopen-2023-003475. RMD Open. 2023. PMID: 37709528 Free PMC article.

See all "Cited by" articles

References

1. Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed
1. Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed
1. Akizuki S, Ishigaki K, Kochi Y, et al. . PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes. Ann Rheum Dis 2019;78:509–18. 10.1136/annrheumdis-2018-214116 - DOI - PubMed
1. Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and Tyk2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed
1. Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, Jazf1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed

LinkOut - more resources

Full Text Sources
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed

[2] Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 2016;12:605–20. 10.1038/nrrheum.2016.137 - DOI - PubMed

[3] Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed

[4] Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. Arthritis Res Ther 2012;14:211. 10.1186/ar3844 - DOI - PMC - PubMed

[5] Akizuki S, Ishigaki K, Kochi Y, et al. . PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes. Ann Rheum Dis 2019;78:509–18. 10.1136/annrheumdis-2018-214116 - DOI - PubMed

[6] Akizuki S, Ishigaki K, Kochi Y, et al. . PLD4 is a genetic determinant to systemic lupus erythematosus and involved in murine autoimmune phenotypes. Ann Rheum Dis 2019;78:509–18. 10.1136/annrheumdis-2018-214116 - DOI - PubMed

[7] Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and Tyk2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed

[8] Cunninghame Graham DS, Morris DL, Bhangale TR, et al. . Association of NCF2, IKZF1, IRF8, IFIH1, and Tyk2 with systemic lupus erythematosus. PLoS Genet 2011;7:e1002341. 10.1371/journal.pgen.1002341 - DOI - PMC - PubMed

[9] Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, Jazf1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed

[10] Gateva V, Sandling JK, Hom G, et al. . A large-scale replication study identifies TNIP1, PRDM1, Jazf1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009;41:1228–33. 10.1038/ng.468 - DOI - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

Affiliations

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

LinkOut - more resources

Full Text Sources

Research Materials

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Related information

LinkOut - more resources

Full Text Sources

Research Materials