Plasma Gelsolin Depletion (PGD)
After injury—either from a pathogen attack or a trauma, systemic levels of plasma gelsolin can rapidly become depleted. In cases of overwhelming injury or concurrent co-morbidities, levels can rapidly decline below a critical threshold. Because plasma gelsolin is secreted constitutively by every cell in the body, there is no emergency mechanism to increase production, leaving the body unable to prevent the spread of inflammation as well as compromising its ability to fight pathogens.
In a broad range of published human studies, PGD correlates with morbidity and mortality in both acute and chronic diseases. Depletion occurs with the onset of injury or infection and predicts increased morbidity and mortality across a broad spectrum of clinical presentations as noted below.
- Sepsis, Septic Shock
- Acute rheumatic carditis
- Lyme Neuroborreliosis
- Tick-borne encephalitis
- Idiopathic Pneumonia Syndrome (IPS) after HSCT
- Neonatal BronchoPulmonary Dysplasia
- Acute Lung Injury
- Surgical Trauma
- Traumatic Brain Injury
- Ischemic Stroke
- Hemorraghic Stroke
- Diabetes Type 2
- Rheumatoid Arthritis, SLE
- Pre-term labor
- Myocardial Infarction
- Acute Liver Failure
- Chronic Renal Disease/ESRD
- Pediatric atopic disease
- Alzheimer’s Disease, Downs
- Multiple Sclerosis
Example 1: pGSN Levels in Surgical ICU Predict Outcomes
SURGICAL ICU: pGSN levels lower than 61 mg/L ( ~25% of normal values) predicted longer ICU stay, prolonged ventilator use and increased risk of death independent of APACHE II score.
Source: Lee et al, Annals of Surgery, 243:39 9-403 (2006)
For example, in a study of patients in Intensive Care Unit (ICU) after surgery, plasma gelsolin levels of all patients were below normal values and remained relatively stable over 5 days. ICU survivors had significantly higher levels of pGSN compared with ICU non-survivors (p=0.02). In multivariate analyses, only pGSN remained an independent predictor of death in surgical ICU patients (OR=36.89, p=0.04).
Other studies confirm these findings in both acute and chronic disease.
Example 2: pGSN Levels in Renal Disease Predict Outcomes
PGD is a powerful predictor for END-STAGE RENAL DISEASE patients: Greater than 3-fold increase in 1-year mortality in lowest v. highest pGSN groups, independent of other risk factors.