Type I interferon detection in autoimmune diseases: challenges and clinical applications

ABSTRACT

Introduction

Accumulating data highlights that the dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ-specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease biomarkers.

Areas covered

Here, we summarize current knowledge regarding the role of type I IFNs in the major systemic, as well as organ-specific, autoimmune disorders, including prominent inflammatory CNS disorders like multiple sclerosis.

Expert opinion

Type I IFN involvement and its clinical associations in a wide spectrum of autoimmune diseases represents a promising area for research aiming to unveil common pathogenetic pathways in systemic and organ-specific autoimmunity.

KEYWORDS:

• Type I interferons
• systemic autoimmune disorders
• organ specific autoimmune disorders
• interferon signaling
• genetics
• therapeutic targets

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Glossary

ACA: anticentromere antibodies

AGS: Aicardi-Goutieres syndrome

ANA: antinuclear antibodies

anti-ACPA: anti-citrullinated protein antibodies

anti-La/SSB: anti–Sjögren’s-syndrome-related antigen B autoantibody

anti-Ro/SSA: anti–Sjögren’s-syndrome-related antigen A autoantibody

aPL: antiphospholipid antibodies

APS: antiphospholipid syndrome

APOBEC: Apolipoprotein B mRNA editing enzyme

APS: Antiphospholipid syndrome

ATA: Anti-topoisomerase I

ATD: Autoimmune Thyroiditis

BAFF: B cell activating factor

cGAS: cyclic guanosine monophosphate–adenosine monophosphate synthase

CD: Crohn’s disease

CNS: Central Nervous System

CSF: Cerebrospinal fluid

CXCL: chemokine (C-X-C motif) ligand

DDX58: DEAD box helicase 58

DM: Dermatomyositis

dsDNA: double stranded DNA

EAE: Experimental autoimmune encephalitis

EPST1: Epithelial Stromal Interaction 1

GD: Graves’ disease

GWAS: Genome wide association studies

HT: Hashimoto’s thyroiditis

IBD: Inflammatory Bowel Disease

ICs: Immunocomplexes

IFIH1: Interferon-induced helicase 1

IFI44L: Interferon Induced Protein 44 Like

IFIT1: Interferon Induced Protein with Tetratricopeptide Repeats 1

IFNAR: Interferon-A receptor

IFNs: Interferons

IIT: interferon-induced thyroiditis

IL: interleukin

ILD: Interstitial lung disease

IRAK1: Interleukin-1(IL-1) receptor associated kinase 1

IRAK4: Interleukin-1(IL-1) receptor associated kinase 4

IRF: Interferon regulatory factor

ISG: interferon stimulated genes

ISGF3: IFN-stimulated gene factor 3

ISRE: Interferon stimulated response elements

JAK: Janus kinase

LINE1 or L1: Long interspersed nuclear element 1

LPS: Lipopolysaccharide

LY6E: Lymphocyte Antigen 6 Family Member E

MALT: Mucosa-associated lymphoid tissue

MDA5: Melanoma differentiation-association protein 5

MHC: Major histocompatibility complex

MOG: Myelin oligodendrocyte glycoprotein

MOG-IgG+: myelin oligodendrocyte glycoprotein antibody-associated CNS demyelination

MS: Multiple Sclerosis

MSG: Minor salivary gland

MX-1: MX dynamin like GTPase 1

MyD88: Myeloid differentiation factor 88

NHL: non-Hodgkin’s Lymphoma

NMO: Neuromyelitis optica

NMOSD: Neuromyelitis optica spectrum disease

NOD: Non-obese diabetic

OAS1: 2ʹ-5ʹ-oli-goadenylate synthetase 1

OAS3: 2ʹ-5ʹ-Oligoadenylate Synthetase 3

PBC: Primary biliary cholangitis

PBMCs: Peripheral blood mononuclear cells

pDCs: Plasmacytoid dendritic cells

PRR: Pattern recognition receptors

PTPN22: Protein tyrosine phosphatase non-receptor 22

RA: Rheumatoid arthritis

RIG-I: Retinoic acid-inducible gene 1

RNP: ribonucleoprotein

RRMS: relapsing remitting multiple sclerosis

RSAD2: Radical S-adenosyl methionine domain containing 2

SF: synovial fluid

SLE: Systemic Lupus Erythematosus

SNP: single-nucleotide polymorphism

SPMS: secondary progressive multiple sclerosis

SS: Sjögren’s syndrome

SSc: Systemic Sclerosis

STAT: Signal transducer and activator of transcription

STING: Stimulatory interferon genes protein

T1D: Type 1 Diabetes

TCR: T-cell receptor

TLR: Toll-like receptor

TORCH: Toxoplasmosis, Other Agents, Rubella, Cytomegalovirus, and Herpes Simplex

TRAF3: TNF receptor-associated factor

TRAIL-M: Tumor necrosis factor-related apoptosis-inducing ligand

TREX-1: Three-prime repair exonuclease 1

TYK: Tyrosine kinase

UC: ulcerative colitis

USP18: Ubiquitin specific peptidase

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.