Study shows route of bladder antigens to lymph tissues

Atlanta-Bladder antigens travel to local and distant lymphoid tissues and enter the circulation, where they can travel as far as the spleen, according to results of a new study from the Feinberg School of Medicine at Northwestern University, Chicago. The study, which the authors say is the first functional study of antigen trafficking from the bladder, may further researchers' understanding of bladder cancer immunotherapies and potentially aid in the development of a vaccine for urinary tract infections.

Presence in urine of immunoglobulin A (IgA) and immunoglobulin G (IgG) after a urinary tract infection are evidence of an adaptive immune response. However, the mechanisms of this immune response and the lymphoid tissues that serve the bladder have not been characterized. The goal of the Northwestern study was to identify the lymphoid tissues that drain the bladder using a murine model. The researchers found that antigens incorporated into the bladder subsequently progressed to the lymph nodes and spleen, they reported at the AUA annual meeting here.

"Antigen trafficking from the bladder to lymphoid tissue has not been previously demonstrated. The adaptive immune response to bladder antigens is an area that has not been explored and may play an important role in a number of disease processes," said, Amanda M. Macejko, MD, a urology resident at Northwestern working with Anthony Schaeffer, MD, and colleagues.

The beads were quickly taken up by the bladder. Sixty minutes after insertion, beads were found in all three layers of the organ. By 24 hours, beads were clustered in the urothelium. Beads clustered in the inguinal lymph nodes within 5 minutes of insertion and remained there for the next 24 hours. Some beads trafficked to the lumbar lymph nodes within 5 minutes, but clustering did not begin in this node until 60 minutes after insertion.

Surprisingly, beads also traveled to the distant cervical lymph nodes within 5 minutes, although fewer beads were seen in this node than were seen in the more proximal nodes. Beads also traveled to the spleen, presumably by entering the circulatory system. Splenic beads were sparse through the 60-minute period, but significant bead clustering was observed by the 24-hour time point.

"My experiments thus far have been primarily using model antigens; namely, latex beads, which may not traffic in the same manner as pathogens," Dr. Macejko explained. "Perhaps future studies will attempt to demonstrate actual antigen presentation in the lymphoid organs and will address whether antigen trafficking is different in a previously infected host."

Preliminary data using fluorescent staining showed that bacteria may follow the same path as the beads.

"A better understanding of the adaptive immune response to bladder antigens will perhaps improve our knowledge of the mechanisms of current bladder cancer immunotherapies and may also help in the production of a succesful UTI vaccine," Dr. Macejko said.