THE PARAPROTEINS IN SYSTEMIC CAPILLARY LEAK SYNDROME

Systemic capillary leak syndrome (SCLS) is a rare disease characterize d by episodes of collapse due to rapid transfer of considerable volume s of plasma from the intravascular to the extravascular compartment. T he pathogenesis of this disease is unknown. The diagnosis is made larg ely on clinical grounds, and investigations are unhelpful. The only co nsistent abnormality is that an IgG paraprotein is found in most patie nts, raising the possibility that the paraprotein may be involved in t he pathogenesis of the disease. Reduction of the paraprotein level in our patient was associated with remission. Blood samples from three SC LS patients and one probable SCLS have been studied. All patients had monoclonal IgG paraproteins. The purified paraproteins were all of IgG 1 subclass and had kappa light chains. However, they differed in size and charge. Antibodies against each of the paraproteins were raised in rabbits. Affinity-purified anti-idiotypic antibodies were tested for cross-reactivity against the other paraproteins using immunoblotting a nd Ouchterlony assay. These assays showed that the anti-idiotypic anti bodies reacted only with the immunizing paraprotein and not with any o f the other paraproteins, i.e. that the paraproteins do not share a co mmon idiotype. Paraproteins did not bind to cultured endothelial cells , either unactivated or following activation with interferon-gamma (IF N-gamma), IL-2 or IL-6. In addition, we were unable to demonstrate any cytotoxicity towards cultured human endothelial cells by paraprotein alone, or in the presence of neutrophils (pronounced neutrophilia bein g a feature of attacks). The relationship between the paraproteins and the disease remains unclear. It is likely that additional, as yet uni dentified, factors are required for the paraprotein to lead to capilla ry leak.