C4d Deposits on the Surface of RBCs in Trauma Patients and Interferes With Their Function

Objective:� Complementsystemisactivatedinpatientswith� trauma.� Althoughcomplementactivationispresumedtocon- tributetoorgandamageandconstitutionalsymptoms,� littleis� knownabouttheinvolvedmechanisms.� Becausecomplement� componentsmaydepositonRBCs,�weaskedwhethercomple- mentdepositsonthesurfaceofRBCintraumaandwhethersuch� depositionaltersRBCfunction. Design:�Aprospectiveexperimentalstudy. Setting:�Researchlaboratory. Subjects:�Bloodsamplescollectedfrom�42�traumapatientsand� 21�healthydonors. Intervention:�None. Measurements and Main Results:�RBCandserawerecollected� fromtraumapatientsandcontroldonors.�RBCsfromtraumapatients� (n�=�40)�werefoundtodisplaysignificantlyhigheramountsofC4d� ontheirsurfacebyflowcytometrycomparedwithRBCsfromcon- trol�(n = 17) (p�<�0.01).�IncreasedamountsofiC3bwerefoundin� traumasera�(n�=�27)�(vs�12�controls,�p�<�0.01)�byenzyme-linked� immunosorbentassay.�IncubationofRBCfromuniversaldonors� (typeO,�Rhnegative)�withtraumasera�(n�=�10)�promotedC4d� depositionontheirsurface�(vssixcontrols,�p <�0.05).�Complement- decoratedRBC�(n�=�6)�displayedlimitedtheirdeformability�(vssix� controls,�p�<�0.05)�intwo-dimensionalmicrochannelarrays.�Incuba- tionofRBCwithtraumasera�(n�=�10)�promotedthephosphoryla- tionofband�3,�acytoskeletalproteinimportantforthefunctionofthe� RBCmembrane�(vseightcontrols,�p�<�0.05),�andalsoaccelerated� calciuminflux� (n�=�9)�andenhancednitricoxideproduction�(n = 12) (vsfourandeightcontrolsrespectively,�p�<�0.05)�inflowcytometry. Conclusions:�Ourstudyfoundthepresenceofextensivecomple- mentactivationintraumapatientsandpresentsnewevidencein� supportofthehypothesisthatcomplementactivationproducts� depositonthesurfaceofRBC.�SuchdepositioncouldlimitRBC� deformabilityandpromotetheproductionofnitricoxide.�Ourfind- ingssuggestthatRBCintraumapatientsmalfunctions,�which� mayexplainorgandamageandconstitutionalsymptomsthatis� notaccountedforotherwisebypreviouslyknownpathophysio-