Photo by Daniel Gay
Results of preclinical research may explain why people with blood type O often get more severely ill from cholera than people with other blood types.
The study suggests that, in people with blood type O, cholera toxin hyperactivates a key signaling molecule in intestinal cells.
And high levels of that molecule, cyclic adenosine monophosphate (cAMP), lead to excretion of electrolytes and water—in other words, diarrhea.
“We have shown that blood type influences how strongly cholera toxin activates intestinal cells, leading to diarrhea,” said study author James Fleckenstein, MD, of Washington University School of Medicine in Saint Louis, Missouri.
Dr Fleckenstein and his colleagues reported these findings in The American Journal of Tropical Medicine and Hygiene.
Cholera is caused by Vibrio cholerae, a bacterium that infects cells of the small intestine.
Epidemiologists first noticed 4 decades ago that people with blood type O were more likely to be hospitalized for cholera than people with other blood types, but the reasons for the difference had never been determined.
Although the blood group antigens—A, B, AB, and O—are best known for their presence on red blood cells, they also are found on the surface of many other cell types, including the cells that line the intestine.
To find out what effect cholera toxin has on intestinal cells carrying different blood group antigens, Dr Fleckenstein and his colleagues used clusters of intestinal epithelial stem cells, called enteroids, that can be grown in the lab and differentiated into mature intestinal cells.
The researchers treated 4 groups of enteroids with cholera toxin—2 derived from people with blood type A and 2 from people with blood type O—and measured the amount of cAMP inside the cells. Enteroids from the other 2 blood types—B and AB—were not available at the time the study was done.
The researchers found that levels of cAMP were roughly twice as high in the cells with the type O antigen than in the cells with type A antigen, suggesting that people with type O antigen who were exposed to cholera toxin would suffer more severe diarrhea.
“It is well-established that high levels of this molecule lead to diarrhea, so we’re making the assumption that higher levels lead to even more diarrhea,” said study author F. Matthew Kuhlmann, MD, of Washington University School of Medicine.
“Unfortunately, we have no way directly to link the responses to the volume of diarrhea and, therefore, the severity of disease.”
The researchers confirmed their enteroid results in an intestinal cell line originally derived from a person with blood type A. The cell line was modified to produce the type O antigen instead.
The team found that cholera toxin induced roughly double the amount of cAMP in cells with type O antigen than in those with type A.
Dr Fleckenstein said the researchers are not sure why cholera toxin induces different responses in cells with different blood group antigens on their surfaces.
“The cholera toxin is known to bind weakly to the ABO antigens, so they may be acting as decoys to draw the toxin away from its true target,” Dr Fleckenstein said. “It may be that the type O antigen just isn’t as good of a decoy as the type A antigen.”
