The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and potentially life-treating vascular disorder of unknown etiology. SCLS is characterized by dramatic and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered increased attention during the last several years because of the resemblance of its initial presentation to more common disorders such as systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses. Although approximately 70-80% of patients with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS), any contribution of the paraprotein to acute flares is unknown. To identify circulating factors that contribute to the onset of acute SCLS crises, we performed transcriptomic profiling of paired peripheral blood mononuclear cell fractions obtained from patients during acute attacks and convalescent intervals using microarray. 61 genes were significantly up- or downregulated more than 2.5 fold in acute samples relative to baseline. One of the most upregulated genes was ADM, which encodes the vasoactive peptide adrenomedullin. The ADM surrogate pro-ADM was markedly elevated in SCLS acute sera compared to remission samples or sera from healthy controls. Monocytes and endothelial cells (ECs) from SCLS subjects expressed significantly more ADM in response to proinflammatory stimuli compared to healthy control cells. Application of ADM to ECs exerted protective effects on vascular barrier function. These results suggest a pathogenic contribution of ADM to the profound pressor-resistant hypotension that characterizes the initial stages of SCLS.

Peripheral blood mononuclear cells (PBMC) were collected from Systemic Capillary Leak Syndrome patients during a SCLS crisis or convalescent interval. Samples for both intervals, crisis (epi) and convalescent (bas), were successfully hybridized for 7 patients. An additional 5 patients are represented by a single disease interval, for a total of 19 samples.

Systemic capillary leak syndrome (Clarkson's Disease) - Rare disease+ (2021 ICD-10-CM code* = '+ https://rarediseases.info.nih.gov/diseases/1084/systemic-capillary-leak-syndrome)

Signal data was extracted from the image files with the Gene Expression module (v. 1.9.0) of the GenomeStudio software (v. 2011.1) from Illumina, Inc. Signal intensities were converted to log 2 scale. Probes that didn't show detection p-value < 0.1 in at least 2 arrays were removed from the dataset. After filtering probes, quantile normalization was applied across all arrays.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE97287