Autoimmune hemolytic anemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S; Shyam Patel [2]
Overview
Pathophysiology
Warm autoimmune hemolytic anemia
The pathophysiology of warm autoimmune hemolytic anemia involves immunoglobulin G (IgG) antibodies binding to red blood cells at a temperature of 37 degrees Celcius. [1] The designation of warm is based on the fact the optimal binding temperature is 37 degrees Celcius, or normal body temperature. The IgG antibodies are typically polyclonal, meaning that they recognize a variety of antigens.[2] Macrophages bind to the antibody-coated red blood cells via the Fc receptors and result in extravascular destruction. The Fc receptors include Fc-gammaRI (CD64), Fc-gammaRII (CD32), and Fc-gammaRIII (CD16). In 15-20% of cases, the autoantibody involved in IgA.[2] It has been shown that induction of autoimmune hemolytic anemia is controlled by an immunosuppressive population of T lymphocytes known as regulatory T cells.[1]
Role of the Complement System
The complement system plays a role in both extravascular hemolysis and intravascular hemolysis in autoimmune hemolytic anemia.
- Extravascular hemolysis: The pathophysiology of extravascular hemolysis in autoimmune hemolytic anemia involves destruction of red blood cells outside the blood vessels and inside the liver and spleen. This is largely due to complement protein C3b-mediated phagocytosis of red blood cells. This process begins with the C3 convertase, which leads to production of complement protein C3b. This protein normally functions to opsonize bacteria and prevent infection, as part of the innate immune system. However, in pathological conditions such as autoimmunity, C3b binds to the surface of red blood cells. Opsonization by C3b triggers the macrophages of the reticuloendothelial system to phagocytose these opsonized cells via complement receptors on the surface of macrophages. This phagocytosis occurs extravascularly, typically in the liver or spleen.
- Intravascular hemolysis: The pathophysiology of intravascular hemolysis in autoimmune hemolytic anemia involves destruction of red blood cells inside the blood vessels. This is largely due to activation of the terminal complement system.[2] This complement cascade begins with complement protein C5, which is activated to C5a and C5b by the C5 convertase. C5a is a potent anaphylactic molecule, C5b is a membrane-bound protein that binds to downstream complement molcules, such as C6 though C9. The union of C5b and C6 though C9 forms the membrane attack complex. This complex can exert direct cytotoxic activity via the creation of pores in red blood cell membranes, resulting in cell lysis intravascularly.[2]
Excess complement activation
In some cases, the complement system can become activated very strongly, resulting in excess immune activation and red blood cell destruction, which can be lethal. This is due in part to a feedforward loop or positive feedback system, in which activation of the initial components of the complement cascade triggers activation of additional complement components.[2]
References
- ↑ 1.0 1.1 Mqadmi A, Zheng X, Yazdanbakhsh K (2005). "CD4+CD25+ regulatory T cells control induction of autoimmune hemolytic anemia". Blood. 105 (9): 3746–8. doi:10.1182/blood-2004-12-4692. PMC 1895013. PMID 15637139.
- ↑ 2.0 2.1 2.2 2.3 2.4 Berentsen S (2015). "Role of Complement in Autoimmune Hemolytic Anemia". Transfus Med Hemother. 42 (5): 303–10. doi:10.1159/000438964. PMC 4678321. PMID 26696798.