Theparaproteins insystemic capillary leaksyndrome

SUMMARY Systemic capillary leak syndrome (SCLS) isa raredisease characterized byepisodes ofcollapse dueto rapidtransfer ofconsiderable volumesofplasmafromtheintravascular to theextravascular compartment. Thepathogenesis ofthis disease isunknown. Thediagnosis ismadelargely on clinical grounds, andinvestigations are unhelpful. Theonlyconsistent abnormality isthatan IgG paraprotein isfoundinmostpatients, raising thepossibility that theparaprotein may beinvolved in thepathogenesis ofthedisease. Reduction oftheparaprotein level inour patient was associated with remission. Bloodsamples fromthree SCLSpatients andone probable SCLShavebeenstudied. All patients hadmonoclonal IgGparaproteins. Thepurified paraproteins were allofIgG1subclass and hadK light chains. However, theydiffered insizeandcharge. Antibodies against eachofthe paraproteins wereraised inrabbits. Affinity-purifie d anti-idiotypic antibodies were tested for crossreactivity against theother paraproteins using immunoblotting andOuchterlony assay.These assays showed that theanti-idiotypic antibodies reacted onlywiththeimmunizing paraprotein andnotwith any oftheotherparaproteins, i.e. thattheparaproteins do notshare a common idiotype. Paraproteins didnotbindtocultured endothelial cells, either unactivated or following activation withinterferon-gamma (IFN-y), IL-2or IL-6. Inaddition, we were unable todemonstrate any cytotoxicity towards cultured humanendothelial cells byparaprotein alone, orinthepresenceof neutrophils (pronounced neutrophilia being a feature ofattacks). Therelationship between the paraproteins andthedisease remains unclear. Itislikely thatadditional, asyetunidentified, factors arerequired fortheparaprotein toleadtocapillary leak.