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Expression and Metabolomic Profiling in Axial Spondyloarthritis

  • Spondyloarthritis (M Khan, Section Editor)
  • Published:
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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.

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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

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Authors and Affiliations

  1. Faculty of Medicine and Genetics, Memorial University of Newfoundland, 154 LeMarchant Rd, St. John’s, Newfoundland and Labrador, A1C 5B8, Canada

    Darren D. O’Rielly, Guangju Zhai & Proton Rahman

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  1. Darren D. O’Rielly
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  2. Guangju Zhai
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  3. Proton Rahman
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Correspondence to Darren D. O’Rielly.

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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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This article is part of the Topical Collection on Spondyloarthritis

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O’Rielly, D.D., Zhai, G. & Rahman, P. Expression and Metabolomic Profiling in Axial Spondyloarthritis. Curr Rheumatol Rep 20, 51 (2018). https://doi.org/10.1007/s11926-018-0756-y

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