Skip to main content

Blood-Mediated Inflammatory Reaction (IBMIR) and Prevention of IBMIR

  • Chapter
  • First Online:
Glycoimmunology in Xenotransplantation
  • 75 Accesses


In transplantation, function loss of grafts is primarily observed in the early time of transplantation, mainly by two known responses of the instant blood-mediated inflammatory reaction (IBMIR) and hyperacute rejection (HR) [1]. It was reported that the first few hours have been reported to display the IBMIR after cell infusion of xenoantigenic islets [2]. IBMIR is characteristic of innate inflammatory responses and thrombotic pathway displayed by a serial reaction complement activation, immune cell infiltration, platelet adhesion, and coagulation [3]. IBMIR is frequently coupled with thrombosis and releases inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), and IL-8. Thrombin fundamentally activates platelets. In addition, thrombin can activate innate immune cells of monocytes and neutrophils. Islets-producing tissue factors mainly cause the IBMIR as a causing factor [2, 4]. Therefore, the thrombosis reaction is prevented by blocking of tissue factors in vitro [3]. The IBMIR is also reported in three different transplantations of allo-, auto-, and xenotransplantation for islets [5], as also caused by incompatible species between thrombotic factors of humans and regulatory molecules of pigs. IBMIR is explained to be not only a response occurred in transplantation of allogeneic and xenogeneic islets, but also a responsive phenomenon to the islets and the highly immunogenic cells surrounded with acinar tissues [5]. However, such hurdles are now resolved by α1,3Gal-T KO animals and transgenic gene manipulation of human genes of CD46/CD55/CD59 complement regulators [6]. Using the genetic engineering technology in the immunological-challenged baboon model, HR- and IBMIR-based phenomena have been prevented by the transgenic islets of pigs. Like the HR, IBMIR can be mitigated by genetically disrupting the α1,3Gal-T gene and by transducing human CD46, CD55, and CD59 complement regulators as transgenic genes, respectively, as the blood mediates inflammatory rejection and the regulators protect the inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions


  1. Bennet W, Sundberg B, Groth CG, et al. Incompatibility between human blood and isolated islets of Langerhans: a finding with implications for clinical intraportal islet transplantation? Diabetes. 1999;48:1907–14.

    Article  CAS  PubMed  Google Scholar 

  2. Moberg L, Johansson H, Lukinius A, et al. Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation. Lancet (London, England). 2002;360:2039–45.

    Article  CAS  PubMed  Google Scholar 

  3. Moberg L, Korsgren O, Nilsson B. Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood. Clin Exp Immunol. 2005;142:125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ji M, Yi S, Smith-Hurst H, et al. The importance of tissue factor expression by porcine NICC in triggering IBMIR in the xenograft setting. Transplantation. 2011;91:841–6.

    Article  PubMed  Google Scholar 

  5. Naziruddin B, Iwahashi S, Kanak MA, et al. Evidence for instant bloodmediated inflammatory reaction in clinical autologous islet transplantation. Am J Transplant. 2014;14:428–37.

    Article  CAS  PubMed  Google Scholar 

  6. Hawthorne WJ, Salvaris EJ, Phillips P, et al. Control of IBMIR in neonatal porcine islet xenotransplantation in baboons. Am J Transplant. 2014;14:1300–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

Copyright information

© 2024 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kim, CH. (2024). Blood-Mediated Inflammatory Reaction (IBMIR) and Prevention of IBMIR. In: Glycoimmunology in Xenotransplantation. Springer, Singapore.

Download citation

Publish with us

Policies and ethics