Discovery of a Potential Human Serum Biomarker for Chronic Seafood Toxin Exposure Using an SPR Biosensor

Abstract

Domoic acid (DA)-producing harmful algal blooms (HABs) have been present at unprecedented geographic extent and duration in recent years causing an increase in contamination of seafood by this common environmental neurotoxin. The toxin is responsible for the neurotoxic illness, amnesic shellfish poisoning (ASP), that is characterized by gastro-intestinal distress, seizures, memory loss, and death. Established seafood safety regulatory limits of 20 μg DA/g shellfish have been relatively successful at protecting human seafood consumers from short-term high-level exposures and episodes of acute ASP. Significant concerns, however, remain regarding the potential impact of repetitive low-level or chronic DA exposure for which there are no protections. Here, we report the novel discovery of a DA-specific antibody in the serum of chronically-exposed tribal shellfish harvesters from a region where DA is commonly detected at low levels in razor clams year-round. The toxin was also detected in tribal shellfish consumers’ urine samples confirming systemic DA exposure via consumption of legally-harvested razor clams. The presence of a DA-specific antibody in the serum of human shellfish consumers confirms long-term chronic DA exposure and may be useful as a diagnostic biomarker in a clinical setting. Adverse effects of chronic low-level DA exposure have been previously documented in laboratory animal studies and tribal razor clam consumers, underscoring the potential clinical impact of such a diagnostic biomarker for protecting human health. The discovery of this type of antibody response to chronic DA exposure has broader implications for other environmental neurotoxins of concern.

Long Term Memory Outcome of Repetitive, Low-Level Dietary Exposure to Domoic Acid in Native Americans

“…The first was reliance on self-reported consumption data and average DA levels at source beaches to estimate exposure. Despite our best efforts [ 29 ], there is currently no known diagnostic biomarker for identifying DA exposure. Such a biomarker would be essential for specifically identifying the extent of human exposure and its relationship to memory outcomes.…”

“…In response to questions about the potential human health impacts of repetitive or cumulative sub-acute exposures to putatively “safe” levels of dietary DA exposure a cohort of 500 Native American (NA) adults residing on the NW Pacific coast. Early findings of this four-year cohort study [ 7 ] and others [ 29 , 30 ] found that repetitive or cumulative sub-acute exposures to putatively “safe” levels of DA in razor clams ( Siliqua patula ) in the US Pacific NW were at risk for memory decline. Specifically, people who consumed 15 or more razor clams per month demonstrated a mild decrement in performance (ASP in attenuated form).…”

Marine Biotoxins and Seafood Poisoning

“…Regarding the development and optimization of methods for toxin detection, Chen and colleagues [5] optimized clean-up procedures based on immunoaffinity column purification before mass spectrometry detection, providing an improved way to detect the amnesic shellfish poisoning toxin domoic acid (DA), in an array of matrices. Lefebvre et al [6] describes a DA-specific antibody in the human serum and report DA-chronic exposure to certain groups of shellfish consumers. Finally, Hayashi et al [7] investigated the combined effect of okadaic acid and mycotoxins that are considered emerging toxins in the marine environment, in human intestinal cell lines.…”