Assessment of specific antibodies as biological indicators of human chronic exposure to microcystins.

Cyanobacteria can produce potent natural toxins known as cyanotoxins. Blooms of cyanobacteria, produced mainly as result of the pollution of water bodies with excessive amounts of phosphorus, represent a severe environmental problem; not only do they affect the normal equilibrium of the aquatic ecosystem but may also affect animal and human health. The occurrence of algal blooms have been increasing globally (it has been recently reported in at least 100 countries) and it has been considered by WHO as an emerging public health issue. The toxic effects of cyanotoxins have been thoroughly demonstrated in laboratory experiments, however, the effects on humans and the extent of these effects have been more difficult to assess. Epidemiological research is difficult as there are no specific symptoms or routine biomarkers to diagnose intoxication with cyanotoxins, in particular those cases associated with chronic exposure. The objectives of this study were to assess the exposure of a population settled near a lake with recurrent cyanobacteria blooms and to investigate the presence of biological markers of chronic exposure to cyanotoxins, in particular the microcystins (MCs). We first investigated the exposure of the population to cyanobacteria by using a questionnaire on how the population used the water and by analyzing water samples for the presence of cyanobacteria and total microcystins (TMCs). Secondly, we investigated the presence of biological indicators by analyzing the biochemical and immunological parameters in sera of the exposed population. The questionnaires and the water analyses revealed that the population under study (n = 47) is exposed to several exposure routes. The biochemical analyses of the sera showed the alteration of at least one hepatic enzyme in 25% of the exposed people, but this cannot be associated solely to MCs exposure. On the contrary, the immunological analyses, which included microcystin-LR specific antibodies IgE and IgG, showed significant differences between the exposed and non-exposed groups. The presence of MCs specific antibodies confirms the exposure to MCs. We propose the study of specific antibodies as a non-complex biomarker to detect chronic exposure to the toxin and to assist epidemiological studies.

Galectin-1 confers immune privilege to human trophoblast: implications in recurrent fetal loss.

Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confers immune privilege to human trophoblast cells through the modulation of a number of regulatory mechanisms. Gal1 was mainly expressed in invasive extravillous trophoblast cells of human first trimester and term placenta in direct contact with maternal tissue. Expression of Gal1 by the human trophoblast cell line JEG-3 was primarily controlled by progesterone and pro-inflammatory cytokines and impaired T-cell responses by limiting T cell viability, suppressing the secretion of Th1-type cytokines and favoring the expansion of CD4(+)CD25(+)FoxP3(+) regulatory T (T(reg)) cells. Targeted inhibition of Gal1 expression through antibody (Ab)-mediated blockade, addition of the specific disaccharide lactose or retroviral-mediated siRNA strategies prevented these immunoregulatory effects. Consistent with a homeostatic role of endogenous Gal1, patients with recurrent pregnancy loss showed considerably lower levels of circulating Gal1 and had higher frequency of anti-Gal1 auto-Abs in their sera compared with fertile women. Thus, endogenous Gal1 confers immune privilege to human trophoblast cells by triggering a broad tolerogenic program with potential implications in threatened pregnancies.

Circulating anti-galectin-1 antibodies are associated with the severity of ocular disease in autoimmune and infectious uveitis.

PURPOSE: Galectin (Gal)-1, an endogenous lectin found at sites of immune privilege, plays a critical role in the regulation of the immune response. Therapeutic administration of Gal-1 or its genetic delivery suppresses chronic inflammation in experimental models of autoimmunity. The purpose of this work was to investigate the occurrence of circulating anti-Gal-1 antibodies in patients with autoimmune and infectious uveitis as potential determinant factors of disease progression. METHODS: IgG, IgE, and IgA anti-Gal-1 antibodies were assessed by ELISA and Western blot in sera from patients with autoimmune (n = 47) and infectious (n = 15) uveitis compared with healthy control subjects (n = 30). The frequency of anti-Gal-1 antibodies was examined in patients experiencing poor clinical outcome (n = 21) or good evolution (n = 9). Anti-Gal-1 antibodies were eluted by incubating patient sera with nitrocellulose filters adsorbed with rGal-1. The ability of these antibodies to recognize retinal tissue was assessed by ELISA, Western blot, and immunohistochemistry. RESULTS: IgE, IgG, and IgA anti-Gal-1 antibodies were increased in sera from patients with autoimmune uveitis (P < 0.001 vs. controls) and toxoplasmic retinochoroiditis (P < 0.001). The level of anti-Gal-1 IgE and IgG antibodies was associated with progressive disease and poor outcome in autoimmune and infectious uveitis. Furthermore, these antibodies strongly immunoreacted with retinal lysates and recognized retinal structures mainly photoreceptors in retinal sections. CONCLUSIONS: Anti-retinal Gal-1 antibodies are present in sera from patients with uveitis and can be associated with the progression of ocular disease, suggesting their potential use in follow-up observations of these patients.