A new murine model of primary autoimmune hemolytic anemia, a type of cold agglutinin disease, has been created to further study disease pathways.

The mouse model shares characteristics of primary AIHA such as age-related onset, splenomegaly, extramedullary erythropoiesis, hemolysis, anemia, and higher frequency of females, according to an article published in Frontier In Immunology.

“This model can be used to provide new insights into the underlying mechanisms in the initiation of idiopathic AIHA,” the authors said. The animal model was created by crossing HEL-OVA-Duffy mice with OTII T-cell receptor mice and produced antierythrocyte autoantibodies related to sex and increased with age.

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The autoantibodies ultimately led to modulation of red blood cell (RBC) antigens, fixation of the complement system, and anemia. The mice also displayed spleens that were larger and heavier than control animals and those that did not express autoantibodies, and the splenic architecture was distorted with the enlargement of white pulp areas and a decrease in the size of the red pulp.

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Histology revealed increased levels of hemosiderin-containing macrophages as well as large megakaryocyte-like cells. The murine model displayed increased levels of RBC progenitor cells but decreased numbers of mature RBCs, indicating that erythropoiesis is dysregulated.

“These data demonstrate that, upon RBC autoantibody production, extramedullary erythropoiesis occurred in the spleen,” the authors mentioned. “As extramedullary erythropoiesis is a compensatory mechanism for insufficient bone marrow-derived RBC production, evaluation of RBC precursors in the bone marrow revealed that production of autoantibodies correlated with reduced frequencies of progenitors.”

No significant differences in cytokine production were observed between the mice with and without autoantibodies. There were also no significant differences in cytokine levels before and after the production of autoantibodies within the same animals. This indicated that events leading to increased cytokine, such as infections or inflammation, were not driving factors of AIHA in the model.

“This is a tractable murine model of AIHA that can serve as a platform to identify key cellular and molecular pathways that are compromised, thereby leading to autoantibody formation, as well as testing new therapeutics and management strategies,” the authors concluded.


Dei Zotti F, Qiu A, La Carpia F, Moriconi C, Hudson KE. A new Murine model of primary autoimmune hemolytic anemia (AIHA). Front Immunol. 2021;12:752330. doi:10.3389/fimmu.2021.752330