Whipple´s disease is caused by chronic infection with the bacterium Tropheryma whippelii. Anything else about it´s pathogenesis is less certain, or unclear.

A peroral route of infection is very likely, but the real source of infection is unknown.

Lessons from its epidemiology indicate:
1. Whipple´s disease is rare, but T. whippelii is apparently not rare,
2. Whipple´s disease presents exclusively in adults (>30 years), but not in children and adolescents,
3. Whipple´s disease is much more common in males (70%), than in females (30%),
4. There are no concurrent infections in relatives of patients,
5. There are no concurrent infections in unrelated partners of patients.

Together, these aspects are in favour of an acquired individual disposition, but militate against a genetic background of Whipple´s disease.

Possibly there is an acquired immunological deficiency. In fact, various immunologial deficits were observed (see table), but in more than just one type of immune cells.

Meanwhile, experimental studies on the infection biology have started.