Prognostic implications of declining plasma gelsolin levels after allogeneic stem cell transplantation.
The idiopathic pneumonia syndrome (IPS) represents a common and often fatal complication of hematopoietic stem cell transplantation (HSCT). Gelsolin is a highly conserved actin-binding protein normally present in plasma that may serve a basic physiological role in limiting acute lung injury of diverse etiologies. We hypothesized that depletion of circulating gelsolin following HSCT might play a permissive role in the pathogenesis of IPS. Plasma gelsolin levels were measured by immunoblotting in frozen samples obtained weekly from 24 patients undergoing allogeneic HSCT. Patients with and without IPS were similar with respect to age, diagnosis, histocompatibility differences between donor and recipient, and conditioning regimen. Mean gelsolin levels in the 9 patients with rapidly fatal IPS were significantly lower than those in patients without this complication by week 3 after HSCT (101 +/- 61 mg/L versus 221 +/- 54 mg/L; P =.0002). Seven (88%) of the 8 patients with gelsolin levels of less than 100 mg/L in the first month after HSCT died from IPS within 3 months; conversely, gelsolin levels fell to less than 100 mg/L in 7 (78%) of the 9 patients who died from IPS within 3 months of HSCT (P =.0007). These findings suggest that gelsolin levels shortly after allogeneic HSCT can predict the later development of fatal IPS. Gelsolin replacement in selected transplant patients may offer a novel strategy to prevent or reverse IPS.
DiNubile
Mark J
MJ
Division of Infectious Diseases, Department of Medicine, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Camden, NJ, USA. mark_dinubile@merck.com
Stossel
Thomas P
TP
Ljunghusen
Olof C
OC
Ferrara
James L M
JL
Antin
Joseph H
JH
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D018260:Gelsolin / Q000097:blood*; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D006648:Histocompatibility; D006801:Humans; D015151:Immunoblotting; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D011014:Pneumonia / Q000097:blood* / Q000209:etiology / Q000401:mortality; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012795:Sialoglycoproteins / Q000627:therapeutic use; D013577:Syndrome; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014809:Vitamin D-Binding Protein / Q000097:blood
D018260:Gelsolin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D014809:Vitamin D-Binding Protein