We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models.
- Authors
Paul, Kausik; Hernández-Armengol, Rosario; June Young Lee; Che-Yu Chang; Shibata, Tomohiro; Yamashita, Michifumi; Jefferies, Caroline; Gibb, David R.
- Abstract
During transfusion of red blood cells (RBCs), recipients are exposed to both ABO and non-ABO 'minor' antigens. RBC donor units and recipient RBCs are not routinely matched for non-ABO antigens. Thus, recipients are exposed to many RBC alloantigens that can lead to RBC alloantibody production and subsequent clinically significant hemolysis. RBC alloantibodies also significantly limit the provision of compatible RBC units for recipients. Prior studies indicate that the frequency of RBC alloimmunization is increased during inflammatory responses and in patients with autoimmune diseases. Still, mechanisms contributing to alloimmune responses in patients with autoimmunity are not well understood. More than half of adult patients with systemic lupus erythematosus (SLE) produce type 1 interferons (IFNa/b) and express IFNa/b stimulated genes (ISGs). Previously, we reported that IFNa/b promote RBC alloimmune responses in the pristane mouse model, which develops a lupus-like phenotype that is dependent on IFNa/b signaling. However, it is unclear whether IFNa/b or the lupus-like phenotype induces alloimmunization in lupus models. Therefore, we tested the hypothesis that IFNa/b promotes RBC alloimmune responses in lupus by examining alloimmune responses in IFNa/b-independent (MRL-lpr) and IFNa/b-dependent (pristane) lupus models. Whereas pristane treatment significantly induced interferon-stimulated genes (ISGs), MRL-lpr mice produced significantly lower levels that were comparable to levels in untreated WT mice. Transfusion of murine RBCs that express the KEL antigen led to anti-KEL IgG production by pristanetreated WT mice. However, MRL-lpr mice produced minimal levels of anti-KEL IgG. Treatment of MRL-lpr mice with recombinant IFNa significantly enhanced alloimmunization. Collectively, results indicate that a lupus-like phenotype in preclinical models is not sufficient to induce RBC alloantibody production, and IFNa/b gene signatures may be responsible for RBC alloimmune responses in lupus mouse models. If these findings are extended to alternate pre-clinical models and clinical studies, patients with SLE who express an IFNa/b gene signature may have an increased risk of developing RBC alloantibodies and may benefit from more personalized transfusion protocols.
- Subjects
BLOOD group antigens; ALLOIMMUNITY; AUTOIMMUNE diseases; LABORATORY mice; RED blood cell transfusion; ANIMAL disease models; TYPE I interferons; SYSTEMIC lupus erythematosus
- Publication
Frontiers in Immunology, 2024, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.1304086