The paraproteins in systemic capillary leak syndrome

Abstract

SUMMARY Systemic capillary leak syndrome (SCLS) is a rare disease characterized by episodes of collapse due to rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. The pathogenesis of this disease is unknown. The diagnosis is made largely on clinical grounds, and investigations arc unhelpful. The only consistent abnormality is that an IgG paraprotein is found in most patients, raising the possibility that the paraprotein may be involved in the pathogencsis of the disease. Reduction of the paraprotein level in our patient was associated with remission. Blood samples from three SCLS patients and one probable SCLS have been studied. All patients had monoclonal IgG paraproteins. The purified paraproteins were all of IgG1 subclass and had k 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 and Ouchtcrlony assay. These assays showed that the anti-idiotypic antibodies reacted only with the immunizing paraprotein and not with any of the other paraproteins. i.e. that the paraproteins do not share a common idiotype. Paraproteins did not bind to cultured endothelial cells, either unaclivated or following activation with interferon-gamma (IFN-γ). IL-2 or IL-6. In addition, we were unable to demonstrate any cytotoxicity towards cultured human endothelial cells by paraprolein alone, or in the presence of neutrophils (pronounced neutrophilia being a feature of attacks). The relationship between the paraproteins and the disease remains unclear. It is likely that additional, as yet unidcntilied. factors arc required for the paraprotein to lead to capillary leak.