Tissue-specific autoantibodies in haemolytic anaemia.

S Worlledge
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引用次数: 4

Abstract

Therehasbeenarenewal ofinterest inrecent years inthepathogenesis ofantibody-mediated redcell destruction. Mostoftheexperimental workhasbeen donewithalloantibodies, butassumedly autoantibodies lead toredcell destruction inasimilar manner. Thispaperattempts tocorrelate theresults ofthese experiments withthefindings inpatients with positive antiglobulin testsand autoimmune haemolytic anaemia (AIHA). Knownandspeculative methods ofredcell destruction LYSIS BY COMPLEMENT Onemolecule ofIgMantibody boundtotheredcell surface istheoretically able toactivate thewhole of thecomplement sequence andlead tolysis ofthered cell. Twomolecules ofIgGclose together onthecell membrane areneeded tostart thesamesequence. MostIgMredcell antibodies will bindatleast some ofthecomponents ofcomplement (although there areimportant exceptions) while, oftheothers, only IgGlandIgG3bindcomplement readily. Forlysis tooccur active C8mustenter thepreformed channels onthecell surface formed byC5-7anddamage the membrane. C9 catalyses thisprocess (MullerEberhard, 1975). Ifmembranes lysed bycomplement areexamined withanelectron microscope 'holes' willbeseen (Humphrey andDourmashkin, 1965). Withhuman complement these areabout100nm indiameter regardless ofwhether thecomplement wasfixed by antibody ornotandregardless ofthespecificity of theantibody. Thissize istoosmall forhaemoglobin toescape andconsequently waterandions aredrawn into theredcell until itbursts (Rosse etal., 1966). Probably allantibodies intheABO,Lewis, P,orJ systems arepotentially lytic butthenumberthat causemarkedhaemolysis invitro isrelatively small. Rareantibodies suchasanti-Vel areoften lytic, and veryoccasional examples ofanti-Jka andanti-Dia will lyse redcells thathavenotbeentreated with enzymes. Ifradiolabelled B orA redcells aregiven toavolunteer withapotent lytic anti-A orBinthe plasma theydisappear fromthecirculation within a fewminutes, haemoglobin will beseenintheplasma and,ifsufficient, intheurine, andverylittle radioactivity will appear intheliver orspleen onscanning (Jandl etal., 1957). Thisdestruction isduetointravascular haemolysis oftheredcells bycomplement andcomplement 'holes' will beseenifthemembranes ofthelysed redcells areexamined. MACROPHAGE AND MONOCYTE RECEPTORS FOR COMPLEMENT
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