• Wed. Feb 12th, 2025

Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether -HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir

Byacusticavisual

Oct 29, 2024

Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether -HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir. Electronic supplementary material The online version of this article (10.1186/s12936-018-2400-8) contains supplementary material, which is available to authorized users. Keywords: histidine-rich protein 2 (HRP2), which was the first antigen targeted in commercial assessments [2]. heat-based immune complex dissociation. A pull-down assay reliant on proteins A, G, and L was developed and applied for IgG and IgM capture and subsequent immunoprecipitation of any HRP2 present in immune complexed form. A total of 104 patient samples were evaluated using both methods. Results Immune-complexed HRP2 was detectable in 17% (18/104) of all samples evaluated and 70% (16/23) of HRP2-positive samples. A majority of the patients with samples containing immune-complexed HRP2 had infections (11/18) and were also positive for free HRP2 (16/18). For 72% (13/18) of patients with immune-complexed HRP2, less than 10% of the total HRP2 present was in immune-complexed form. For the remaining samples, a large proportion (?20%) of total HRP2 was complexed with -HRP2 antibodies. Conclusions Endogenous -HRP2 antibodies form immune complexes with HRP2 in the symptomatic patient population of a low-transmission area in rural Southern Zambia. For the majority of patients, the percentage of HRP2 in immune complexes is low and does not affect HRP2-based malaria diagnosis. However, for some patients, a significant portion of the total HRP2 was in immune-complexed form. Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether -HRP2 antibodies Namitecan affect HRP2 detection for this portion of the transmission reservoir. Electronic supplementary material The online version of this article (10.1186/s12936-018-2400-8) contains supplementary material, which is available to authorized users. Keywords: histidine-rich protein 2 (HRP2), which was the first antigen targeted in commercial tests [2]. HRP2 is a 30?kDa water-soluble protein found in the parasite and host erythrocyte cytoplasm and on the surface of infected red blood cells [3]. The precise function of HRP2 remains unconfirmed, though the primary structure of HRP2 is highly unique; histidine comprises more than 30% of the primary sequence, which consists largely of AHHAHHAAD and AHHAAD repeat motifs [4]. A cleavable sequence at the N-terminus is Namitecan responsible for export of HRP2, which diffuses into host plasma, allowing for detection in peripheral blood [3, 5]. Clinical concentrations of HRP2 can range from 100?fM to 100?nM, though expression of HRP2 Namitecan varies over the erythrocytic life cycle of the parasite [6C9]. The unique structure of HRP2 makes it an advantageous biomarker for malaria detection; multiple epitope copies on a single protein result in high-avidity interactions with antibodies present in RDTs, leading to effective capture and detection of HRP2. Thus, it is not surprising that the most sensitive RDTs on the market are based on HRP2 detection, though performance varies significantly by manufacturer [10]. Despite these advantages, there are several drawbacks to using HRP2 as the sole diagnostic marker for infections. The biomarker has been shown to persist in circulation up to 52?days beyond successful treatment and parasite clearance [9, 11]. Thus, an HRP2-based test is unable to distinguish between active and recently cleared infections. Additionally, HRP2 is not essential to parasite survival, and clinical isolates with gene deletions have been observed with increasing frequency around the world [12C18]. Infections lacking will result in false-negative results on HRP2-based malaria rapid diagnostics and can threaten elimination efforts. Another potential source of false-negative RDT results in infections before treatment and over 28?days after treatment [25]. HRP2 decreased gradually over time, with HRP2-specific IgM following the same pattern. Mouse monoclonal to GFP Anti-HRP2 IgG titres increased gradually over the 28?days. Importantly, 3 patients who were RDT-negative and microscopy-positive upon enrollment had significantly higher -HRP2 IgM and IgG titres compared to the 42 RDT-positive individuals, indicating that the presence of these circulating antibodies could interfere with HRP2-specific RDTs [25]. More recently, Ho et al. found endogenous -HRP2 antibodies were present in the plasma of 25% of symptomatic malaria patients from Cambodia, Nigeria, and the Philippines and Namitecan 11% of asymptomatic individuals in the Solomon Islands [27]. The group also found that incubating serum from high -HRP2-titre individuals with in vitro parasite culture resulted in a marked decrease in RDT signal for several RDT brands [27]. Both of these studies suggest that the humoral immune response against HRP2 could decrease the detectability of HRP2, resulting in false-negative RDT readings. In direct contrast to the aforementioned reports, two investigations have found an absence of endogenous -HRP2 antibodies in patients from malaria-endemic regions. In a study aimed to determine the immunomodulatory properties of the biomarker, Das et al. found that PBMCs isolated from transmission with the goal of determining the prevalence, class, subclass, and avidity of circulating -HRP2 antibodies [28]. Although these patients had robust levels of antibodies specific for other antigens, including three malaria merozoite surface proteins (MSP1, MSP2,.