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Expression and Metabolomic Profiling in Axial Spondyloarthritis

  • Darren D. O’Rielly
  • Guangju Zhai
  • Proton Rahman
Spondyloarthritis (M Khan, Section Editor)
  • 121 Downloads
Part of the following topical collections:
  1. Topical Collection on Spondyloarthritis

Abstract

Purpose of Review

The purpose of this review is to highlight recent evidence with respect to expression and metabolomic profiling in axial spondyloarthritis (axSpA) that included ankylosing spondylitis (AS).

Recent Findings

AxSpA is not only characterized by the strongest genetic contribution for any complex rheumatic disease but is also influenced by environmental and immunological factors. Large-scale association-based studies have identified over 100 genetic variants contributing to 30% of the genetic risk of ankylosing spondylitis. Recent studies in global expression and metabolomic profiling appear to highlight common themes despite differences in tissues, populations, techniques, and relative paucity of patients in many of these studies.

Summary

Expression studies support a role for immunomodulation and bone remodeling in the pathogenesis and progression of axSpA/AS, while metabolomic studies implicate the importance of the intestinal microbial metabolism as well as fat and choline metabolic pathways in AS.

Keywords

Spondyloarthritis Ankylosing spondylitis Genomics Transcriptomics MicroRNA Metabolomics 

Abbreviations

A1

Adenosine A1 receptor

A2AAR

Adenosine A2A receptor

A2BAR

Adenosine A2B receptor

ANTXR2

Anthrax toxin receptor 2

AS

Ankylosing spondylitis

ATG16L1

Autophagy related 16 like 1

axSpA

Axial spondyloarthritis

ASAS

Assessment of spondyloarthritis international society

ASDAS

Ankylosing spondylitis disease activity score

BASDAI

Bath ankylosing spondylitis disease activity index

BASFI

Bath ankylosing spondylitis functional index

BMD

Bone mineral density

BMP

Bone morphogenetic protein

BMP-2

Bone morphogenetic protein 2

BMP-4

Bone morphogenetic protein 4

BMP-7

Bone morphogenetic protein 7

BXDC5

Brix domain-containing protein 5

CRP

C-reactive protein

CTX

Carboxy-terminal collagen crosslinks

DKK1

Dickkopf-related protein 1

DKK3

Dickkopf-related protein 3

DEGs

Differentially expressed genes

EGFR

Epidermal growth factor receptor

ERA

Enthesitis-related arthritis

ESR

Erythrocyte sedimentation rate

GC-MS

Gas chromatography-mass spectrometry

GO

Gene ontology

GSK3β

Glycogen synthase kinase 3 beta

GWAS

Genome-wide association studies

HLA-B

Human leukocyte antigen B

HSP90AA1

Heat shock protein 90 alpha family class A member 1

IDO

Indoleamine 2,3-dioxygenase

IFN

Interferon

Ihh

Indian hedgehog

IL-1

Interleukin-1

IL-1β

Interleukin-1 beta

IL2RA

Interleukin-2 receptor alpha

IL2RB

Interleukin-2 receptor beta

IL-6

Interleukin-6

IL-17A

Interleukin-17A

IL-22

Interleukin-22

IL-23

Interleukin-23

IL-23R

Interleukin-23 receptor

IRGM

Immunity related GTPase M

lncRNA

Long non-coding RNA

ITM2A

Integral membrane protein 2A

JAK

Janus kinase

JIA

Juvenile idiopathic arthritis

KEGG

Kyoto Encyclopedia of Genes and Genomes

KIR3DL2

Killer cell immunoglobulin-like receptor 3DL2

KREMEN1

Kremen protein 1

LC-MS

Liquid chromatography-mass spectrometry

MAP3K7

Mitogen-activated protein kinase kinase kinase 7

MHC

Major histocompatibility complex

MGP

Matrix gla protein

MIF

Macrophage migration inhibitory factor

miRNA

Micro-ribonucleic acid

MMP-2

Matrix metalloproteinase-2

mRNA

Messenger ribonucleic acid

MMP-1

Matrix metalloproteinase-1

MMP-3

Matrix metalloproteinase-3

MS

Mass spectrometry

mSASSS

Modified stoke ankylosing spondylitis spinal score

NFKB1

Nuclear factor kappa-B p105 subunit

NMR

Nuclear magnetic resonance

NR4A2

Nuclear receptor subfamily 4 group A member 2

OA

Osteoarthritis

OPG

Osteoprotegerin

OPLS-DA

Orthogonal projection to latent structure discriminant analysis

PADI4

Peptidyl arginine deiminase 4

PBMCs

Peripheral blood mononuclear cells

PCA

Principal component analysis

PD-1

Programmed cell death protein 1

PDCD4

Programmed cell death 4

PLS-DA

Partial least squares discriminant analysis

PTGER4

Prostaglandin E2 receptor 4

RA

Rheumatic arthritis

RNAseq

Ribonucleic acid sequencing

SMAD5

SMAD family member 5

SMAD7

SMAD family member 7

SNP

Single nucleotide polymorphism

STAT

Signal transducer and activator of transcription

STAT1

Signal transducer and activator of transcription 1

STAT4

Signal transducer and activator of transcription 4

TG

Triglycerides

Tim-4

T-cell immunoglobulin and mucin domain containing 4

TLR4

Toll-like receptor 4

TLR5

Toll-like receptor 5

TNF

Tumor necrosis factor

TNF-α

Tumor necrosis factor-alpha

TNFAIP

Tumor necrosis factor, alpha-induced protein 3

TNFSF10

TNF superfamily member 10

ucMGP

Uncarboxylated matrix gla protein

VEGF

Vascular endothelial growth factor A

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Rahman reports personal fees from Abbott, AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer, Roche, and UCB grants and personal fees from Janssen, outside the submitted work.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Competing Interests

PR is a consultant to multiple pharmaceutical companies dealing with biologic agents including Abbott, AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB,

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Darren D. O’Rielly
    • 1
  • Guangju Zhai
    • 1
  • Proton Rahman
    • 1
  1. 1.Faculty of Medicine and GeneticsMemorial University of NewfoundlandSt. John’sCanada

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