Oral administration of Domain-I of beta-2glycoprotein-I induces immunological tolerance in experimental murine antiphospholipid syndrome

Asaf Shemer, Rohan Willis, Emilio Gonzalez, Zurina Romay-Penabad, Ora Shovman, Yehuda Shoenfeld, Miri Blank, Howard Amital

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

It is well established that the humoral immunity in antiphospholipid syndrome (APS) is presented by circulating pathogenic anti-β2GPI autoantibodies targeting mainly domain I of the β2GPI protein, playing a major role in the disease pathogenesis. Previously, we have demonstrated that treatment of experimental APS mice with tolerogenic dendritic cells loaded with domain-I was more efficient in tolerance induction than with the whole molecule or domain-V. In the current study we had orally administered a domain-I derivative of the β2GPI molecule, as a new therapeutic approach to induce oral tolerance in this mouse model of APS. BALB/c mice immunized with β2GPI, were fed with either domain-I, domain-V derivative or the complete β2GPI protein. β2GPI immunized mice developed experimental APS which were fed with domain-I significantly had decreased fetal loss (p < 0.004), a lower size of thrombi (p < 0.001) and lower circulating anti-β2GPI Abs in comparison to mice fed with domain-V or PBS (p < 0.002). Likewise, Domain-I fed mice had a lowered inflammatory response, exhibited by decreased expression of inflammatory cytokines (IFNγ, IL-6, IL-17) and elevated production of IL-10 anti-inflammatory cytokine by splenocytes. Moreover, the anti-inflammatory response in the domain-I fed APS mice was associated with increased circulating miRNA variations (155, 146, 182, 98) by RT-PCR, which are associated with immunomodulation of the immune network. We propose that oral tolerance with domain-I can be a novel therapy for patients with APS.

Original languageEnglish (US)
Pages (from-to)98-103
Number of pages6
JournalJournal of Autoimmunity
Volume99
DOIs
StatePublished - May 1 2019

Fingerprint

Antiphospholipid Syndrome
Oral Administration
Anti-Inflammatory Agents
Cytokines
Immunomodulation
Interleukin-17
Humoral Immunity
MicroRNAs
Interleukin-10
Autoantibodies
Dendritic Cells
Interleukin-6
Proteins
Thrombosis
Therapeutics
Polymerase Chain Reaction

Keywords

  • Antiphospholipid syndrome
  • Antiphospholipid syndrome
  • Autoimmunity
  • Beta2glycoprotein-I
  • Oral tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Oral administration of Domain-I of beta-2glycoprotein-I induces immunological tolerance in experimental murine antiphospholipid syndrome. / Shemer, Asaf; Willis, Rohan; Gonzalez, Emilio; Romay-Penabad, Zurina; Shovman, Ora; Shoenfeld, Yehuda; Blank, Miri; Amital, Howard.

In: Journal of Autoimmunity, Vol. 99, 01.05.2019, p. 98-103.

Research output: Contribution to journalArticle

Shemer, Asaf ; Willis, Rohan ; Gonzalez, Emilio ; Romay-Penabad, Zurina ; Shovman, Ora ; Shoenfeld, Yehuda ; Blank, Miri ; Amital, Howard. / Oral administration of Domain-I of beta-2glycoprotein-I induces immunological tolerance in experimental murine antiphospholipid syndrome. In: Journal of Autoimmunity. 2019 ; Vol. 99. pp. 98-103.
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abstract = "It is well established that the humoral immunity in antiphospholipid syndrome (APS) is presented by circulating pathogenic anti-β2GPI autoantibodies targeting mainly domain I of the β2GPI protein, playing a major role in the disease pathogenesis. Previously, we have demonstrated that treatment of experimental APS mice with tolerogenic dendritic cells loaded with domain-I was more efficient in tolerance induction than with the whole molecule or domain-V. In the current study we had orally administered a domain-I derivative of the β2GPI molecule, as a new therapeutic approach to induce oral tolerance in this mouse model of APS. BALB/c mice immunized with β2GPI, were fed with either domain-I, domain-V derivative or the complete β2GPI protein. β2GPI immunized mice developed experimental APS which were fed with domain-I significantly had decreased fetal loss (p < 0.004), a lower size of thrombi (p < 0.001) and lower circulating anti-β2GPI Abs in comparison to mice fed with domain-V or PBS (p < 0.002). Likewise, Domain-I fed mice had a lowered inflammatory response, exhibited by decreased expression of inflammatory cytokines (IFNγ, IL-6, IL-17) and elevated production of IL-10 anti-inflammatory cytokine by splenocytes. Moreover, the anti-inflammatory response in the domain-I fed APS mice was associated with increased circulating miRNA variations (155, 146, 182, 98) by RT-PCR, which are associated with immunomodulation of the immune network. We propose that oral tolerance with domain-I can be a novel therapy for patients with APS.",
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