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Investigation of possible autoimmune responses induced by organophosphate exposure - VM02116

The objectives of this study are:Ÿ To investigate whether exposure to organophosphate pesticides is associated with an humoral autoimmune response caused by phosphorylation of normal proteins in the body.Ÿ To investigate whether any characterised autoantibody response to organophosphate-induced phosphorylation can be linked with either symptoms reported by some individuals or the nature of the exposure (i.e. degree of exposure or specific OPs). These objectives can be investigated by detecting the presence and level of autoantibodies against OP-phosphorylated protein structures in blood plasma samples. We have access to appropriate plasma samples which are banked after analysis in our routine biological monitoring service for OP-exposed workers and accidental exposure, and through our contacts with pressure-groups of those individuals claiming OP-induced ill-health. Access to appropriate control populations is also available. We propose investigating relevant autoantibody responses in three cohorts of subjects, one with a range of OP exposures, a second group of subjects reporting long-term symptoms that they associate with OP exposure and an appropriate control group.Chronic neurological sequelae have been recognised after exposure to certain OPs at levels causing acute, anticholinergic symptoms. Regulatory authorities have responded to such evidence, for example by revoking the registration of such OPs or imposing more stringent measures controlling exposure. However, diverse neurological/behavioural symptoms are still being reported by a small number of individuals who claim the symptoms are OP-related, but often with no evidence of any exposure associated with acute anticholinergic symptoms. This continues to cause problems for government departments and agencies (MAFF, DoH, HSE, DETR) who have responsibility for regulating these chemicals or the nation’s health. The possibility remains that lower OP exposures or specific OP exposures can still be associated with chronic diseases, often including a neurological component (1,2). Currently there is no accepted hypothesis that can explain this problem. We postulate that in certain individuals phosphorylation by OPs of specific proteins may lead to these altered proteins being seen as foreign by the individual’s immune system and thus to an autoimmune response. Depending on the target protein, such autoimmune response may have long-term health implications. Several well-characterised neurological diseases, such as myasthenia gravis, Guillain-Barre and Eaton-Lambert syndromes, multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy have autoimmune origins. An OP-induced autoimmune response may explain the lack of a simple dose-effect relationship and the overall low prevalence of those reporting possible OP-related chronic neurological symptoms. Such relationships are well founded in studies of occupational allergy and toxin-induced autoimmune phenomena carried out by our laboratory (3-7).The hypothesis of autoimmune response causing ill health after reactive chemical exposure, including OPs, has been suggested by various sources, including from within the pressure groups and some commercial sevices offering “diagnosis and treatment”. Currently no appropriate scientific investigation has been carried out to establish the validity of the hypothesised biological mechanism.It is envisaged that the results from this study, whether substantiating the hypothesis or not, will be published in the peer-reviewed scientific press.
1. Identification of the three study cohorts of the appropriate size and gain ethical approval for the study.2. Preparation of capture antigens to be prepared for detecting phosphorylation autoantibodies in subjects’ blood samples and the development of appropriate microtitre based assays systems3. Undertake ELISA- based screening of plasma samples using capture antigens noted in 2.4. Calculate prevalence of positive samples. Further investigation of those individuals with “positive” autoantibodies by standardised health (25) and historical exposure questionnaire.5. Report to funding departments and the study will be published in the peer-reviewed scientific press
Project Documents
• Final Report : Investigation of possible autoimmune responses induced by organophosphate exposure   (291k)
Time-Scale and Cost
From: 2001

To: 2003

Cost: £87,266
Contractor / Funded Organisations
Health & Safety Laboratory
Animal Health              
Plants and Animals              
Veterinary Medicines              
Fields of Study
Animal Health
Veterinary Medicine