Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease).
BACKGROUND
Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses. Although approximately 70-85% of patients with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS), any contribution of the paraprotein to acute flares is unknown.


PROCEDURE
To identify circulating factors that might trigger acute SCLS crises, we profiled transcriptomes of paired peripheral blood mononuclear cell fractions obtained from patients during acute attacks and convalescent intervals by microarray.


RESULTS
This study uncovered 61 genes that were significantly up- or downregulated more than 2.5-fold in acute samples relative to respective baselines. One of the most upregulated genes was ADM, which encodes the vasoactive peptide adrenomedullin. A stable ADM protein 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 elicited protective effects on vascular barrier function, suggesting a feedback protective mechanism in SCLS.


CONCLUSIONS
Since ADM has established hypotensive effects, differentiating between these dual actions of ADM is crucial for therapeutic applications aimed at more common diseases associated with increased ADM levels.
['Xie|Zhihui|Z|', 'Chen|Wei-Sheng|WS|', 'Yin|Yuzhi|Y|', 'Chan|Eunice C|EC|', 'Terai|Kaoru|K|', 'Long|Lauren M|LM|', 'Myers|Timothy G|TG|', 'Dudek|Arkadiusz Z|AZ|', 'Druey|Kirk M|KM|']
D000208:Acute Disease D053607:Adrenomedullin D000368:Aged D015415:Biomarkers D019559:Capillary Leak Syndrome D016022:Case-Control Studies D002478:Cells, Cultured D004730:Endothelium, Vascular D005260:Female D020869:Gene Expression Profiling D005786:Gene Expression Regulation D006801:Humans D007963:Leukocytes, Mononuclear D008297:Male D008875:Middle Aged D009000:Monocytes
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