Antibody Secreting Cells (ASC) in Human Clostridium Difficile Infection, Colonization, and Reoccurrence

Clostridium difficile infection (CDI) is a common nosocomial pathogen that plagues patients because of it relatively high rate of recurrence. Although diagnosis for primary CDI is very sensitive, there are not tests to predict recurrence. Recent human clinical trials show monocolonal antibodies to toxin A & B are protective for recurrent disease and some natural history studies suggest generation of serum C. difficile antibodies at 2-4 weeks may be protective. But, late appearance of serum antibodies makes it difficult since the majority of recurrences occur within 4 weeks. An early biomarker is required for a test to prognosticate C. difficile recurrence. Interestingly, cells responsible for the rise in serum cells (ASC) specific for C. difficile will be an early immune measure that can predict disease recurrence making targeted therapy with new expensive monocolonal antibodies and invasive fecal transplant treatments possible. This application will also provide building blocks to develop a "novel C. difficile ASC assay" for the identification of C. difficile toxin A & B antibodies early in disease to prognosticate disease recurrence.