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Abstract Number: 1780

Microbiome in Offspring of Ankylosing Spondylitis Patients

Matthew Stoll1, Kimberly DeQuattro 2, Zhixiu Li 3, Henna Sawhney 4, Maria Castillo 4, Pamela F. Weiss 5, Peter Nigrovic 6, Lynn Punaro 7, Kenneth Schikler 8, Barbara Edelheit 9, John Reveille 10, Matthew Brown 3 and Lianne Gensler 11, 1University of Alabama at Birmingham, Birmingham, AL, 2University of California, San Francisco, San Francisco, CA, 3Queensland University of Technology, Queensland, Australia, 4University of California in San Francisco, San Francisco, CA, 5Children's Hospital of Philadelphia, Philadelphia, PA, 6Boston Children's Hospital, Boston, MA, 7Texas Scottish Rite Hospital, Dallas, TX, 8University of Kentucky, Louisville, KY, 9Connecticut Children's Medical Center, Hartford, CT, 10University of Texas McGovern Medical School, Houston, 11University San Francisco California, San Francisco, CA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ankylosing spondylitis (AS) and juvenile idiopathic arthritis-enthesitis (ERA), microbiome

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Session Information

Date: Monday, November 11, 2019

Session Title: 4M095: Spondyloarthritis Including Psoriatic Arthritis – Basic Science (1776–1781)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Spondyloarthritis (SpA) results from the interplay between genetic and environmental factors. An emerging factor is the human intestinal microbiota, which multiple studies in children and adults have shown to be abnormal in SpA patients, including enthesitis-related arthritis (ERA) and Ankylosing Spondylitis (AS). Considering the microbiota pathogenic, we may have the opportunity to both identify an at-risk population and consider ways to modify their microbiota. The purpose of this study was to analyze the microbiota of healthy children at risk for SpA, stratified by HLA-B27, and to compare these healthy children to HLA-B27+ ERA patients.

Methods: Children age 5 – 18 years (along with their AS parent) were examined by a rheumatologist for evidence of SpA. Human DNA as well as fecal specimens were collected from both parent and children. Microbiota specimens were subject to amplification of the V4 region of the ribosomal RNA gene, which was sequenced on the Illumina MiSeq device. Host SNP genotyping was performed with the Illumina Global Screening Array, a single nucleotide polymorphism (SNP) microarray with 760,000 markers, from which HLA types were imputed using SNP2HLA. The Quantitative Insight into Microbial Ecology was used for quality control as well as clustering into operational taxonomic units (OTUs) using uclust. The OTU table was imported as a phyloseq object for further processing, visualization, and diversity analysis. DeSeq2 was used for FDR-corrected comparisons of abundances of the major taxa, and the Random Forest algorithm was used to predict the development of arthritis based upon the microbiota contents.

Results: Fecal specimens were obtained on 28 offspring of AS patients, of whom 18 were HLA-B27+; one had a SpA diagnosis at study enrollment. Healthy offspring were compared to 29 additional children with HLA-B27+ ERA (ILAR criteria) recruited from 6 sites. Among ERA patients, clustering by diagnosis was present (Figure 1; p = 0.004, adonis). Following transformations and adjustment for multiple comparisons, 20 OTUs were significantly associated with diagnosis state, of which four (Bifidobacterium adolescentis, Ruminococcaceae, and Clostridiaceae higher in controls; Bacteroides fragilis higher in ERA) were identified among the top 10 most associated with the diagnosis in the Random Forest model (Figure 2). Comparison of the HLA-B27+ to negative offspring revealed clustering by genotype (Figure 3; p = 0.05) and demonstrated that several of the OTUs that distinguished healthy offspring from patients (e.g. Ruminococcus gnavus, higher in ERA vs offspring and HLA-B27+ vs HLA-B27- offspring) were also significantly associated with genotype.

Conclusion: Our data identified several bacteria associated with HLA-B27 in healthy at-risk children and ERA patients, and thus may identify a high-risk population that could be the target of future preventative efforts.

Visualization of the microbiota of healthy offspring -red- compared to ERA patients -blue-. NMDS = nonmetric multidimensional scaling, an ordination method similar to principal coordinates analysis.

Results of Random Forests analysis evaluating the microbiota as a Predictor of arthritis. The top 10 most important OTUs -as reflected by the MeanDecreaseGini are shown.- The higher the MeanDecreaseGini, the more important the variable -in this case, OTU- is for classification of the sample. Two of the organisms were each represented by two different OTUs.

Visualization of the microbiota of HLA-B27- offspring -red- compared to HLA-B27+ offspring -blue- using NMDS. The microbiota of the child diagnosed with SpA is depicted as a triangle.


Disclosure: M. Stoll, None; K. DeQuattro, None; Z. Li, None; H. Sawhney, None; M. Castillo, None; P. Weiss, None; P. Nigrovic, None; L. Punaro, None; K. Schikler, None; B. Edelheit, None; J. Reveille, Abbvie, 2, CB, 5, Eli Lilly, 2, 5, 8, Janssen, 2, Janssen Research & Development, LLC, 2, Novartis, 5, Pfizer, 2, 5, UCB, 5; M. Brown, None; L. Gensler, AbbVie, 2, 5, Abbvie, 2, 9, Amgen, 2, Amgen, AbbVie and Novartis, 2, Center for Disease Control, 8, Division of Vaccine Injury Compensation, 8, Eli Lilly, 5, 9, Eli Lilly and Company, 9, Galapagos, 5, 9, Galapagos, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, 5, Janssen, 5, 9, Novartis, 2, 5, 9, Pfizer, 2, 9, Spondylitis Association of America, 6, Spondyloarthritis Research and Treatment Network (SPARTAN), 6, UCB, 2, 5, 9, UCB Pharma, 2, 9.

To cite this abstract in AMA style:

Stoll M, DeQuattro K, Li Z, Sawhney H, Castillo M, Weiss P, Nigrovic P, Punaro L, Schikler K, Edelheit B, Reveille J, Brown M, Gensler L. Microbiome in Offspring of Ankylosing Spondylitis Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/microbiome-in-offspring-of-ankylosing-spondylitis-patients/. Accessed January 27, 2023.
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