Update April 04, 2004

From: Dr Gershwin

First, let me thank all of you for helping us to come to the meetings that we have had in Davis, Woodland, Santa Rosa and Belmont. Without your support (and donation of blood, urine and saliva!), our research would likely come to a halt.

Second, let me bring you up to date on what is happening. Thanks to your help, we are nearly 80% done with the largest epidemiological study of PBC in the world. We have interviewed people and controls with PBC in nearly every state and in most large cities. The data is being unblinded and we hope will provide some valuable clues as to how PBC starts.

Also, and thanks to you again, we are able to take some environmental chemicals and inject them into guinea pigs and produce some liver damage. We are still not sure if this is PBC or not, but it is a hot lead and one that we and others will chase until we know for sure.

At the same time, Dr. Carlo Selmi in our lab, continues his vigorous study of novo aromaticivorans. This bug is found in untreated water, in sewage, and also in human saliva and even feces. This bug has a gene which looks strikingly similar to the human mitochondrial antigen. It could well be only a pure serendipity finding but it does raise the question of whether PBC is caused by a combination of chemicals and bacteria. Much of the blood that we collected on Saturday will go towards this study.

We are also trying to figure out why patients with PBC make so much immunoglobulin M in their blood. Dr. Kentaro Kikuchi has been studying this now for almost two years and has identified a gene that may be involved in this process. If so, it would suggest that at least this one gene helps us to explain genetic predisposition. Obviously, much remains to be done.

On the other hand, Dr. Yasu Kimura has just returned to Japan and completed a study of certain enzymes and metabolized drugs and chemicals in the body. He found that a much higher percentage of patients with PBC who have Stage III and Stage IV, have a certain gene involved in chemical detoxification than do patients with PBC who have Stage I or II.

Unfortunately, this genetic analysis seems only useful for a small percentage of patients with PBC, but it does highlight the possibility that there may be other tests to be done to predict severity of PBC.

The lab now has almost 20 people from several countries, all of whom work on PBC. We will be moving to our new building in the Genomics Center in July 2004, since we have so outgrown our space.

M.Eric Gershwin M.D.

Distinguished Professor of Medicine

The Jack and Donald Chia Professor of Medicine

Chief, Division of Rheumatology, Allergy and Clinical immunology

TB 192, One Shields Ave.

University of California at Davis

Davis, California 95616