Antiphospholipid Syndrome

  • Gaafar RagabEmail author
  • William Ruff
  • Derek Pearson
  • Hadi Goubran
  • Martin Kriegel


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.


Antiphospholipid syndrome Microbiome Pathogenesis Autoimmunity The complement system Clinical manifestations Management 




Anti-β2 GP1

Anti-beta 2-glycoprotein-1


Antigen-presenting cells


Antiphospholipid syndrome


Activated partial thromboplastin time


Catastrophic antiphospholipid syndrome


C-reactive protein


Cytochrome P


Dilute Russell viper venom time


Deep vein thrombosis


Enzyme-linked immunosorbent assay


Epithelial cells


Hemolysis, elevated liver enzymes, and low platelet count


Heparin-induced thrombocytopenia



Ig G

Immunoglobulin G

Ig M

Immunoglobulin M


lupus anticoagulant


lymphokine-activated killer


Low molecular weight heparin


Microbe-associated molecular patterns


Myocardial infarction


Nonobese diabetic


Pattern recognition receptors




Short-chain fatty acids


Segmented filamentous bacteria


Systemic lupus erythematosus


T follicular helper cells


T helper 17 cells


Toll-like receptors


Trimethylamine N-oxide




Venous thromboembolism


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Gaafar Ragab
    • 1
    Email author
  • 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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