Changes in salivary proteome following allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is frequently complicated by severe infections and graft-vs-host disease (GVHD). Saliva contains many components of adaptive and innate immune response crucial for local host defenses. Changes in salivary constituents could reflect systemic processes such as immune reconstitution and development of GVHD that occur posttransplant. This study was an initial evaluation of salivary protein changes that occur after allo-HCT.


METHODS
Serially collected saliva samples from 41 patients undergoing allo-HCT were evaluated. Changes in salivary proteome were initially examined by SELDI-TOF mass spectrometry. Individual protein changes were identified by 2-dimensional differential in-gel electrophoresis (2D-DIGE) with subsequent MS/MS sequencing and ELISA.


RESULTS
Significant increases and decreases in multiple salivary proteins that lasted at least 2 months posttransplant were detected by SELDI-TOF mass spectrometry. Lactoferrin and secretory leukocyte protease inhibitor demonstrated elevations 1 month post-HCT that persisted at least 6 months. Secretory IgA (sIgA) levels were decreased 1 month posttransplant, with recovery at approximately 6 months. Levels of salivary beta(2)-microglobulin were elevated at 6 months and correlated with sIgA levels.


CONCLUSIONS
Allo-HCT is associated with long-term changes in several salivary proteins important for innate immune responses. These results support further studies on the association of salivary proteins with posttransplant complications including infections and GVHD.
Imanguli
Matin M
MM
Clinical Research Core, National Institutes of Health, Bethesda, MD 20892, USA.
Atkinson
Jane C
JC
Harvey
Kristen E
KE
Hoehn
Gerard T
GT
Ryu
Ok Hee
OH
Wu
Tianxia
T
Kingman
Albert
A
Barrett
A John
AJ
Bishop
Michael R
MR
Childs
Richard W
RW
Fowler
Daniel H
DH
Pavletic
Steven Z
SZ
Hart
Thomas C
TC
D000328:Adult; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007781:Lactoferrin / Q000032:analysis; D008297:Male; D015999:Multivariate Analysis; D020543:Proteome / Q000737:chemistry*; D012463:Saliva / Q000737:chemistry*; D012471:Salivary Proteins and Peptides / Q000032:analysis*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D014184:Transplantation, Homologous; D001613:beta 2-Microglobulin / Q000097:blood
D007070:Immunoglobulin A; D020543:Proteome; D012471:Salivary Proteins and Peptides; D053481:Secretory Leukocyte Peptidase Inhibitor; D001613:beta 2-Microglobulin; D007781:Lactoferrin