Abstract
BackgroundLittle 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.MethodsUsing 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.ResultsFrom 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.ConclusionThe 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.
Highlights
Serum antibodies are essential components of adaptive immunity, but are involved in the pathogenesis of many autoimmune diseases
The rapid induction of autoantibodies in acute respiratory distress syndrome (ARDS) and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins
Detection of high titer autoantibodies to proinflammatory cytokines in selected ARDS and sepsis patients Based on the hypothesis that anti-cytokine autoantibodies might predispose a patient to infection or inflammation, 24 controls, 35 ARDS and 13 sepsis patients were screened for autoantibodies to a panel of cytokines using Luciferase Immunoprecipitation Systems (LIPS)
Summary
Serum antibodies are essential components of adaptive immunity, but are involved in the pathogenesis of many autoimmune diseases. While much is known about the control of host antibody production following pathogen exposure or vaccination [1], the induction of autoantibodies in human autoimmune and other diseases remains poorly defined. Infection and other environmental insults have been speculated to trigger immune responses by different mechanisms including induction of cytokines, stimulation of toll-like receptors and other pattern recognition. Acute respiratory distress syndrome (ARDS) and severe sepsis are acute inflammatory conditions associated with high morbidity and mortality, often involving multiple organ failure [3,4]. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
