Glycation Inactivation of the Complement Regulatory Protein CD59

A Possible Role in the Pathogenesis of the Vascular Complications of Human Diabetes

  1. Xuebin Qin12,
  2. Allison Goldfine3,
  3. Nicole Krumrei2,
  4. Luciano Grubissich2,
  5. Juan Acosta24,
  6. Michael Chorev2,
  7. Arthur P. Hays5 and
  8. Jose A. Halperin12
  1. 1Hematology Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
  2. 2Laboratory for Translational Research, Harvard Medical School, Boston, Massachusetts
  3. 3Joslin Diabetes Center, Boston, Massachusetts
  4. 4Beth Israel Deaconess Medical Center, Boston, Massachusetts
  5. 5Columbia University, New York, New York
  1. Address correspondence and reprint requests to Dr. Jose A. Halperin, Harvard Medical School, 1 Kendall Square, Building 600, 3rd Floor, Cambridge, MA 02139. E-mail: jose_halperin{at}


Micro- and macrovascular diseases are major causes of morbidity and mortality in the diabetic population, but the cellular and molecular mechanisms that link hyperglycemia to these complications remain incompletely understood. We proposed that in human diabetes, inhibition by glycation of the complement regulatory protein CD59 increases deposition of the membrane attack complex (MAC) of complement, contributing to the higher vascular risk. We report here 1) the generation and characterization of an anti–glycated human CD59 (hCD59) specific antibody, 2) the detection with this antibody of glycated hCD59 colocalized with MAC in kidneys and nerves from diabetic but not from nondiabetic subjects, and 3) a significantly reduced activity of hCD59 in erythrocytes from diabetic subjects, a finding consistent with glycation inactivation of hCD59 in vivo. Because hCD59 acts as a specific inhibitor of MAC formation, these findings provide a molecular explanation for the increased MAC deposition reportedly found in the target organs of diabetic complications. We conclude that glycation inactivation of hCD59 that leads to increased MAC deposition may contribute to the extensive vascular pathology that complicates human diabetes.


  • X.Q. and A.G. contributed equally to this work.

    • Accepted July 6, 2004.
    • Received February 20, 2004.
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