Rapid induction of autoantibodies during ARDS and septic shock.
BACKGROUND
Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS) and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction.


METHODS
Using Luciferase Immunoprecipitation Systems (LIPS), a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time.


RESULTS
From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected.


CONCLUSIONS
The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.
Burbelo
Peter D
PD
Neurobiology and Pain Therapeutics Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA. burbelop@nidcr.nih.gov
Seam
Nitin
N
Groot
Sandra
S
Ching
Kathryn H
KH
Han
Brian L
BL
Meduri
G Umberto
GU
Iadarola
Michael J
MJ
Suffredini
Anthony F
AF
D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D012189:Retrospective Studies; D012772:Shock, Septic / Q000276:immunology*
D001323:Autoantibodies