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  • This study has some limitations First

    2020-11-18

    This study has some limitations. First, the immunoblot analyses performed in the present study did not test for whole retinal antigens. Therefore, we could not exclude the possibility that the clinical features of our cases were caused by the activity of other antiretinal antibodies, although the same is true of previously reported anti-enolase AIR patients. Second, despite our careful enrollment of patients, the retinal involvements seen in this study might have been caused by other diseases such as RP, AMD, and uveitis, all of which were shown to induce higher expression of antiretinal Sweroside than controls.25, 26, 27, 28 Third, the pathogenic role of anti-α-enolase antibody remains incompletely understood. In the present study, however, we detected anti-α-enolase antibody in 27% of the presumed AIR patients, approximately 3 times the rate of patients with ERM and AMD in our preliminary data (10%) and normal subjects in the previous study (9%), suggesting a cause-effect relationship between this antibody and our case series, in concert with the rationale of the cytotoxic epitope in anti-enolase CAR patients.
    Introduction Toxoplasmosis is a global disease caused by Toxoplasma gondii, which infects nearly one-third of the human population in addition to an extraordinary range of vertebrate hosts [1], [2]. T. gondii infection can cause toxoplasmic encephalitis in immunocompromised patients, leading to blindness, abortion, fetal abnormalities and even prenatal death in pregnant women [3], [4]. As an obligate intracellular parasite, Toxoplasma must invade a vertebrate host cell for survival and replication, and the T. gondii invasion process initiates a lytic cycle, leading to cell and tissue destruction that is a hallmark of Toxoplasma pathology [5], [6], [7]. Two asexual forms of T. gondii are present during its life cycle in intermediate hosts, including humans: the rapidly growing tachyzoite and the slowly dividing bradyzoite [8]. During initial infection, the parasite spreads quickly, benefitting from the rapid growth that occurs during the tachyzoite stage, and produces an array of secretory proteins associated with host cell invasion, proliferation and host immune mechanism interference. The most important of these proteins are reported to be parasite excretory/secretory antigens (ESA), which constitute the majority of circulating antigens in sera from hosts with acute toxoplasmosis [9], [10], [11], [12]. Despite significant progress in the study of these proteins, only a limited number of secretory proteins have been discovered to date, and the precise functions of most ESA proteins remain poorly understood. Clearly, the identification of parasite-specific proteins will significantly expand the number of potential targets for therapeutic intervention or diagnostic strategies. Enolase is a highly conserved protein found in many organisms, both prokaryotic and eukaryotic as well as parasitic, with similar catalytic properties among divergent organisms, including glycolytic properties that enable it to convert D-2-phosphoglycerate (2PGA) to phosphoenolpyruvate (PEP) during glycolysis and gluconeogenesis, two metabolic pathways that are often vital to cellular function [8], [13]. Considerable evidence has showed that enolase is a multifunctional protein that is not only essential for pathogen viability but also promotes pathogen–host interactions and contributes to infection and pathogenesis. For example, trypanosomatids have the unique feature of compartmentalizing the major part of the glycolytic pathway inside peroxisome-related organelles called glycosomes. These organelles, most prominent in the bloodstream form of these parasites, notably compartmentalize glycolytic enzymes, contain enolase [14], [15]. Enolase has been considered to be a key player in the metabolism and a probable virulence Sweroside factor of trypanosomatid parasites and represents both an interesting drug target and vaccine candidate [16]. Although enolases are cytosolic enzymes involved in the glycolytic pathway, they can also be secreted or expressed on the surfaces of a variety of eukaryotic cells and bacteria where they mainly act as an important antigenic protein during infection and function as a mediator of microbial virulence in pathogenesis [17], [18], [19], [20], [21]. T. gondii belongs to the phylum Apicomplexa, which also includes several other notable pathogens, such as Plasmodium and Eimeria. In Plasmodium spp., cell surface enolase has been suggested to participate in the tissue invasion process [22], and in Eimeria tenella, enolase also plays a vital role in parasite-host cell interactions [23]. In addition, enolase can be found at the cell surface of numerous other prokaryotic and eukaryotic pathogenic organisms [24], [25], [26]. In addition to its localization at the membrane surface, enolase is secreted by many prokaryotic pathogenic organisms, such as Vibrio parahaemolyticus[13], Borrelia burgdorferi[21], and Streptococcus iniae[27], as well as many parasites, such as E. tenella[23], Echinostoma caproni[28], Fasciola hepatica[29], Giardia lamblia[30] and Schistosoma japonicum[31]. Some enolases excreted to the extracellular environment has been found to mediate both the degradation of host tissues and immune evasion, similar to what has been observed for the human pathogen Streptococcus pyogenes[32] and the insect parasite Aphidius ervi[33]. These location and pathways are, therefore, candidate targets for the development of antiparasite drugs and candidate vaccines against these infection-causing pathogens.