Autoimmune role in OP poisoning?

OUR laboratory has undertaken routine monitoring of workers potentially exposed to OP pesticides for over 25 years, writes Dr Howard Mason, of the Health and Safety Laboratory in Sheffield.

This has included workers manufacturing and formulating pesticides, as well as those using them in horticulture or agriculture. This monitoring has been by blood measurements that relate to the well known anticholinergic effect of OPs in inhibiting a key enzyme, acetylcholinesterase, in normal nerve function. Less than 1 per cent of our monitoring data suggest any anticholinesterase effect of absorbed OPs, and almost invariably at very mild levels with any symptoms being relatively rare and shortterm.

We have therefore been puzzled by the diverse range of long term symptoms reported by some people, especially those sheep dipping using OP dips. They do not seem related to the well characterised, short-term anticholinergic effects caused by significant OP absorption and are apparent in only a relatively small fraction of those people who have been potentially exposed to OPs. We have therefore been interested in whether there are other biological mechanisms which may cause the reported problems.

The Defra/VMD-funded project has been to explore our hypothesis that OPs may cause an autoimmune reaction. This could happen as OPs may not only modify acetylcholinesterase but phosphorylate other proteins in the body. These OP-modified proteins may then possibly be recognised as 'foreign' by an individual's immune system leading to an autoimmune reaction with a range of possible outcomes. While there a number of relatively rare autoimmune diseases that are often associated with a wide range of symptoms, autoimmune phenomena are also found which are not associated with ill-health.

Autoimmune phenomena can be detected by finding antibodies in a blood sample that specifically bind to the modified proteins of interest. Therefore we have undertaken to test blood samples for antibodies that bind to a range of proteins that we have specifically modified by OPs in the laboratory. We have tested blood samples from workers in our routine monitoring scheme for OP exposure where we have evidence that they have had significant OP exposure, as well as blood samples from people who have had little or no OP exposure. The study has been carried out 'blinded' meaning that the analyst does not know which blood samples belong to workers who has been overexposed to OPs and those with no exposure.

Currently we are removing the 'blinding' of samples and analysing the data. Our preliminary conclusion is that there is some evidence of an autoimmune response in some of the workers who have had significant OP exposure. We would stress that from this study there is no evidence that this phenomena is related to ill-health; those workers we tested had no obvious health problems.