Cold Agglutinin Disease
Cold agglutinin disease (CAD) is a rare autoimmune disorder characterized by the production of cold-reactive antibodies that cause the destruction of red blood cells. As a leading autoimmune disease and inflammation research company, we are committed to providing a one-stop solution for the development of CAD therapeutics.
Introduction to Cold Agglutinin Disease
Cold agglutinin disease (CAD) is an autoimmune disorder in which the immune system mistakenly produces antibodies that bind to red blood cells at low temperatures, leading to their destruction and subsequent anemia. The condition is often associated with underlying conditions such as lymphoproliferative disorders or infections, although it can also occur idiopathically. The pathogenesis of CAD involves the production of cold-reactive antibodies, typically of the IgM class, that recognize antigens on the surface of red blood cells. When exposed to cold temperatures, these antibodies bind to the red blood cells, leading to their agglutination and subsequent destruction through complement-mediated lysis.
Fig.1 The classical and terminal complement pathways in cold agglutinin disease. (Berentsen S., et al., 2019)
Drug Discovery and Development for Cold Agglutinin Disease
Corticosteroids, such as prednisone, have been used as first-line therapy for CAD. They work by suppressing the immune response and reducing antibody production. However, their efficacy is variable, and long-term use can lead to significant side effects. Immunosuppressive agents, such as azathioprine or cyclophosphamide, may be considered in refractory cases or to reduce corticosteroid dependence.
In addition, rituximab, a monoclonal antibody that depletes B-cells, has demonstrated favorable outcomes in some cases, leading to reduced autoantibody production and amelioration of symptoms. In recent years, complement-directed therapy can also be used as potential therapeutics. Eculizumab, an anti-C5 monoclonal antibody, has shown effectiveness in inhibiting intravascular hemolysis and reducing transfusion requirements in severe cases.
Our company is at the forefront of developing therapeutics for CAD. Through our extensive R&D capabilities, we are committed to helping global pharmaceutical companies identify new therapeutic targets and develop innovative drugs. If you would like to obtain more information, please click on the link below.
Our Services
At our company, we offer a comprehensive range of services tailored to CAD diagnostics and therapy development. Our expertise in the field allows us to provide cutting-edge solutions for accurate diagnosis, as well as the development of novel therapies. We offer a wide range of diagnostic assays, including cold agglutinin titration, direct antiglobulin test, and flow cytometry, to aid in the diagnosis and monitoring of CAD.
CAD Mouse Models
Through our extensive expertise and cutting-edge technologies, we have successfully developed mouse models that closely resemble the pathophysiological aspects of CAD. Our CAD mouse model exhibits age-related onset, splenomegaly, extramedullary erythropoiesis, hemolysis, anemia, and a higher frequency among females.
CAD Pig Models
Our company recognizes the value of pig models in CAD research, owing to their physiological and immunological similarities to humans. We can employ splenectomized pigs infected with Eperythrozoon suis as an animal model for studying acute porcine eperythrozoonosis, a condition sharing resemblances with CAD in humans.
Our team of experts has successfully developed primary human cell cultures derived from CAD cases, including erythrocytes, immune cells, and endothelial cells. These models are essential for investigating the interactions between cold agglutinins and various cellular components.
Our company has harnessed the potential of organoid technology to develop CAD-specific organoid models, including erythrocyte organoids and immune organoids, enabling us to study the disease in a more physiologically relevant context.
Our state-of-the-art facilities and experienced scientists provide a robust platform for conducting in vitro and in vivo experiments, including pharmacokinetics and pharmacodynamic studies, efficacy assessments, and safety evaluations. In addition to the services and models listed above, we also provide customized services and disease model development services to meet your specific needs. If you are interested in our services, please don't hesitate to contact us.
Reference
- Berentsen S., et al. "Cold agglutinin disease: current challenges and future prospects." Journal of blood medicine (2019): 93-103.