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Paroxysmal Nocturnal Hemoglobinuria pp 67–95Cite as

Complement and PNH

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Abstract

The intravascular hemolysis that is the defining clinical feature of PNH is complement-mediated. PNH erythrocytes undergo spontaneous lysis in vivo because they lack decay-accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), glycosylphosphatidylinositol-anchored proteins, that regulate complement at two different steps in the cascade. DAF controls the formation and stability of the alternative pathway C3 and C5 convertases, whereas CD59 inhibits the terminal pathway by blocking the formation of the cytolytic membrane attack complex. Investigation into the mechanisms underlying the hemolysis of PNH has produced a remarkable number of important discoveries about the workings of the human complement system, including confirmation of the existence of the alternative pathway, characterization of the function of DAF, and discovery of CD59. Insightful analysis of complement sensitivity assays identified the phenotypic mosaicism characteristic of the PNH, revealed the clonal nature of the disease, and demonstrated its origin in the hematopoietic stem cell. Ultimately, research into the basis of the complement-mediated hemolysis of PNH led to development of symptomatically effective therapy for the disease.

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  1. Division of Hematology and Hematologic Malignancies, University of Utah School of Medicine, 30 N 1900 E RM 5C402, Salt Lake City, UT, 84132-2101, USA

    Charles J. Parker M.D.

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  1. Department of Hematology and Ocology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yuzuru Kanakura

  2. Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

    Taroh Kinoshita

  3. Dept of Hematology and Ocology, Osaka University Dept of Hematology and Ocology, Suita, Osaka, Japan

    Jun-ichi Nishimura

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Parker, C.J. (2017). Complement and PNH. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_4

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