A 28-year-old woman with systemic lupus erythematosus (SLE) presents with hemolytic anemia. All of the following pathophysiologic mechanisms contribute to the hemolysis in SLE EXCEPT:

Explanation

## Autoimmune Hemolytic Anemia in SLE: Type II Hypersensitivity **Key Point:** SLE-associated hemolytic anemia is a Type II hypersensitivity reaction driven by IgG anti-RBC antibodies and complement activation. Mast cell degranulation (Type I mechanism) plays NO role in this pathology. ### Mechanisms of Hemolysis in SLE | Mechanism | Antibody/Cell | Result | |-----------|---------------|--------| | Direct complement activation | IgG anti-RBC → C1q → C3b deposition | Membrane attack complex → RBC lysis | | Opsonization | C3b-coated RBCs → CR1 on macrophages | Phagocytosis in spleen | | ADCC | IgG-coated RBCs → Fc receptors on NK/macrophages | Antibody-dependent cytotoxicity | | Immune complex deposition | Circulating IC → RBC surface/complement | Secondary complement activation | **High-Yield:** Autoimmune hemolytic anemia is **Type II hypersensitivity**, NOT Type I. Type I (IgE-mediated mast cell activation) causes anaphylaxis and urticaria, not hemolysis. ### Why Mast Cells Are NOT Involved - Mast cell mediators (histamine, tryptase, leukotrienes) cause vasodilation, smooth muscle contraction, and increased vascular permeability — NOT RBC destruction. - Mast cells are activated by IgE cross-linking, not by IgG or complement. - Type I hypersensitivity is acute and systemic (anaphylaxis); autoimmune hemolysis is chronic and organ-specific. **Clinical Pearl:** In SLE hemolytic anemia, the Coombs test (direct antiglobulin test) is positive because IgG and/or complement are bound to the RBC surface — confirming antibody-mediated destruction, not mast cell involvement. **Warning:** Do NOT confuse the mechanisms of Type I (IgE, mast cells, immediate) and Type II (IgG, complement, antibody-dependent cytotoxicity) hypersensitivity.