Complement activation in diabetic ketoacidosis brains.
The metabolic crisis of diabetic ketoacidosis (DKA) and its treatment can result in the life-threatening complication of clinical brain edema. However, there is limited information available regarding either the pathophysiology or histology of this acute complication. It has been reported that DKA and its treatment are associated with a systemic inflammatory response involving the activation of the complement cascade with increases of SC5b-9 serum level. We studied the brains of two patients, both of whom died as the result of DKA-related brain edema, for the presence of C5b-9, C1q and the expression of the CD59. Apoptosis was also evaluated by the TUNEL method. All regions of the brain demonstrated varying degrees of C5b-9 deposits on neurons, oligodendrocytes and blood vessels. C5b-9 was co-localized with C1q, suggesting the activation of classical pathway. No expression of CD59 was found on neurons, oligodendrocytes or blood vessels in DKA brain, but this complement inhibitor was present on these cells in the normal brain. Rarely, C5b-9 was co-localized with apoptotic neurons and OLG. Our data demonstrate that the metabolic crisis of DKA results in a loss of CD59 expression and assembly of C5b-9 on neurons and oligodendrocytes, suggesting that complement activation and C5b-9 may play a role in the pathophysiology of the brain edema of DKA.
Hoffman
William H
WH
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA.
Cudrici
Cornelia D
CD
Zafranskaia
Ekaterina
E
Rus
Horea
H
D000293:Adolescent; D017209:Apoptosis; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D018957:CD59 Antigens / Q000096:biosynthesis; D003167:Complement Activation / Q000502:physiology*; D015922:Complement C1q / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D016883:Diabetic Ketoacidosis / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology
D018957:CD59 Antigens; D015938:Complement Membrane Attack Complex; D015922:Complement C1q