A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients

Elizabeth Ogunrinde, Zejun Zhou, Zhenwu Luo, Alexander Alekseyenko, Quan Zhen Li, Danielle Macedo, Diane L. Kamen, Jim C. Oates, Gary S. Gilkeson, Wei Jiang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE. Methods: Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first-degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing. Results: First-degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti–double-stranded DNA IgG levels in first-degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first-degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first-degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first-degree relatives (adjusted P [Padj] = 2.13 × 10−12) and SLE patients (Padj = 0.008) but elevated in controls. Conclusions: These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.

Original languageEnglish (US)
Pages (from-to)1858-1868
Number of pages11
JournalArthritis and Rheumatology
Volume71
Issue number11
DOIs
StatePublished - Nov 1 2019

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Microbiota
Systemic Lupus Erythematosus
Autoantibodies
Bacteria
Lipopolysaccharides
Autoantigens
Paenibacillus
Horseshoe Crabs
Microarray Analysis
Ribosomal DNA
DNA Sequence Analysis
Antibody Formation
Immunoglobulin G
Parents
Control Groups

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

Cite this

A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients. / Ogunrinde, Elizabeth; Zhou, Zejun; Luo, Zhenwu; Alekseyenko, Alexander; Li, Quan Zhen; Macedo, Danielle; Kamen, Diane L.; Oates, Jim C.; Gilkeson, Gary S.; Jiang, Wei.

In: Arthritis and Rheumatology, Vol. 71, No. 11, 01.11.2019, p. 1858-1868.

Research output: Contribution to journalArticle

Ogunrinde, E, Zhou, Z, Luo, Z, Alekseyenko, A, Li, QZ, Macedo, D, Kamen, DL, Oates, JC, Gilkeson, GS & Jiang, W 2019, 'A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients', Arthritis and Rheumatology, vol. 71, no. 11, pp. 1858-1868. https://doi.org/10.1002/art.40935
Ogunrinde, Elizabeth ; Zhou, Zejun ; Luo, Zhenwu ; Alekseyenko, Alexander ; Li, Quan Zhen ; Macedo, Danielle ; Kamen, Diane L. ; Oates, Jim C. ; Gilkeson, Gary S. ; Jiang, Wei. / A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients. In: Arthritis and Rheumatology. 2019 ; Vol. 71, No. 11. pp. 1858-1868.
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title = "A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients",
abstract = "Objective: Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE. Methods: Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first-degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing. Results: First-degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti–double-stranded DNA IgG levels in first-degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first-degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first-degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first-degree relatives (adjusted P [Padj] = 2.13 × 10−12) and SLE patients (Padj = 0.008) but elevated in controls. Conclusions: These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.",
author = "Elizabeth Ogunrinde and Zejun Zhou and Zhenwu Luo and Alexander Alekseyenko and Li, {Quan Zhen} and Danielle Macedo and Kamen, {Diane L.} and Oates, {Jim C.} and Gilkeson, {Gary S.} and Wei Jiang",
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T1 - A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients

AU - Ogunrinde, Elizabeth

AU - Zhou, Zejun

AU - Luo, Zhenwu

AU - Alekseyenko, Alexander

AU - Li, Quan Zhen

AU - Macedo, Danielle

AU - Kamen, Diane L.

AU - Oates, Jim C.

AU - Gilkeson, Gary S.

AU - Jiang, Wei

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Objective: Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE. Methods: Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first-degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing. Results: First-degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti–double-stranded DNA IgG levels in first-degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first-degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first-degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first-degree relatives (adjusted P [Padj] = 2.13 × 10−12) and SLE patients (Padj = 0.008) but elevated in controls. Conclusions: These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.

AB - Objective: Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE. Methods: Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first-degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing. Results: First-degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti–double-stranded DNA IgG levels in first-degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first-degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first-degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first-degree relatives (adjusted P [Padj] = 2.13 × 10−12) and SLE patients (Padj = 0.008) but elevated in controls. Conclusions: These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.

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