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Antiphospholipid Syndrome

  • Gaafar Ragab
  • William Ruff
  • Derek Pearson
  • Hadi Goubran
  • Martin Kriegel
Chapter

Abstract

Antiphospholipid syndrome (APS) is a female-biased, systemic autoimmune disorder characterized by thromboembolism and/or miscarriage in the presence of antiphospholipid antibodies (aPLs). Diagnostic tests include the detection of immunoglobulin M or G targeting cardiolipin, β2-glycoprotein I, and/or lupus anticoagulant testing. APS occurs as a primary condition or associated with other systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE), which is discussed in a separate chapter. Evidence from animal models and clinical studies suggests a role for infectious agents in both the generation of aPLs and the triggering of thrombosis and miscarriage. Besides a diagnostic and therapeutic overview of APS, this chapter will cover innate immune and viral triggers followed by infectious agents involved in the induction of transient aPLs. A major focus will be the intestinal microbiota, which encompasses all microbes residing in the gut and has emerged as a potential trigger of APS pathogenesis. Various mechanisms of how the gut microbiota contributes to APS are put forth including cross-reactivity, bystander activation, and epitope spreading. In vitro and vivo evidence from cross-reactive antigens in the microbiome are discussed as well as a role for the microbiota in a spontaneous mouse model of APS, the (NZWxBXSB) F1 hybrid, which is protected upon depletion of gram-positive bacteria via oral vancomycin. In summary, this chapter provides an overview of microbial organisms in the pathogenesis of APS with attention to emerging evidence for the microbiome in the initiation and propagation of pathogenic immune responses in APS.

Keywords

Antiphospholipid syndrome Microbiome Pathogenesis Autoimmunity The complement system Clinical manifestations Management 

Abbreviations

aCL

Anticardiolipin

Anti-β2 GP1

Anti-beta 2-glycoprotein-1

APCs

Antigen-presenting cells

APS

Antiphospholipid syndrome

aPTT

Activated partial thromboplastin time

CAPS

Catastrophic antiphospholipid syndrome

CRP

C-reactive protein

CYP

Cytochrome P

dRVVT

Dilute Russell viper venom time

DVT

Deep vein thrombosis

ELISA

Enzyme-linked immunosorbent assay

EpC

Epithelial cells

HELLPsyndrome

Hemolysis, elevated liver enzymes, and low platelet count

HIT

Heparin-induced thrombocytopenia

IFN

Interferon

Ig G

Immunoglobulin G

Ig M

Immunoglobulin M

LA

lupus anticoagulant

LAK

lymphokine-activated killer

LMWH

Low molecular weight heparin

MAMPs

Microbe-associated molecular patterns

MI

Myocardial infarction

NOD

Nonobese diabetic

PRRs

Pattern recognition receptors

PSA

Polysaccharide

SCFAs

Short-chain fatty acids

SFB

Segmented filamentous bacteria

SLE

Systemic lupus erythematosus

Tfh

T follicular helper cells

Th17

T helper 17 cells

TLR

Toll-like receptors

TMAO

Trimethylamine N-oxide

TMP/SMX

Trimethoprim/sulfamethoxazole

VTE

Venous thromboembolism

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gaafar Ragab
    • 1
  • William Ruff
    • 2
  • Derek Pearson
    • 3
    • 4
  • Hadi Goubran
    • 3
    • 4
  • Martin Kriegel
    • 2
  1. 1.Rheumatology and Clinical Immunology Unit, Department of Internal MedicineCairo UniversityGizaEgypt
  2. 2.Department of ImmunobiologyYale School of MedicineNew HavenUSA
  3. 3.College of MedicineUniversity of SaskatchewanSaskatoonCanada
  4. 4.Saskatoon Cancer CentreSaskatoonCanada

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