Reduced alloimmunization in mice following repeated transfusion with pathogen-reduced platelets

Area of Science:

• Immunology
• Transfusion Medicine
• Biotechnology

Background:

• Allogeneic transfusions can lead to alloimmunization, causing platelet refractoriness and transplant rejection.
• Pathogen reduction with UV light and riboflavin (UV+R) has previously shown to reduce white blood cell immunogenicity and prevent alloimmunization in mice.
• The study investigates if repeated transfusions with pathogen-reduced platelet-rich plasma (PRP) induce breakthrough alloimmunization or tolerance.

Purpose of the Study:

• To determine the efficacy of pathogen-reduced platelet-rich plasma (PRP) in preventing alloimmunization during repeated transfusions.
• To assess whether repeated exposure to pathogen-reduced PRP leads to enhanced tolerance or breakthrough alloimmunization.
• To evaluate the combined effect of pathogen reduction and leukoreduction on transfusion immunogenicity.

Main Methods:

• BALB/cJ mice received weekly transfusions of C57Bl/6J PRP for 2, 4, or 8 weeks.
• PRP was either untreated or pathogen-reduced using UV+R, with or without leukoreduction.
• Alloimmunization was assessed by measuring donor antibody levels, ex vivo cytokine responses, and 24-hour donor platelet recovery.

Main Results:

• Donor antibody levels increased with transfusion frequency but were significantly reduced by UV+R or leukoreduction, with the combination providing maximal protection.
• Priming of ex vivo cytokine responses required white blood cells and remained suppressed with UV+R-treated transfusions.
• Platelet recovery was reduced in naive mice receiving UV+R-treated platelets, and multiply transfused mice showed poor recovery, with minimal serum amounts causing complete donor platelet rejection.

Conclusions:

• Pathogen reduction significantly mitigates alloimmunization in mice undergoing repeated platelet transfusions.
• The combination of pathogen reduction (UV+R) and leukoreduction provides a high level of protection against alloimmunization.
• Repeated transfusions with pathogen-reduced PRP effectively suppress alloimmunization and associated immune responses.