Gromova M, Vaggelas A, Dallmann G
… +1 more, Seimetz D
Biomark Insights
· 2020 · PMID 33343195
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Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current...Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current global regulatory landscape is presented in this article with particular emphasis on the validation and qualification of biomarkers, as well as legal framework for companion diagnostics. Furthermore, this article shows how the number of approved drugs with at least 1 biomarker used during development (biomarker acceptance) is affected by the recent advances in the biomarker regulations. More than half of analysed approvals were supported by biomarker data and there has been a slight increase in acceptance of biomarkers in recent years, even though the growth is not continuous. For certain pharmacotherapeutic groups, approvals with biomarkers are more common than without. Examples include immunosuppressants, immunostimulants, drugs used in diabetes, antithrombotic drugs, antineoplastic agents and antivirals. As a conclusion, potential benefits, challenges and opportunities of using biomarkers in drug discovery and development in the current regulatory landscape are summarised and discussed.
Ali I, Ibrahim ST, Chinnadurai R
… +4 more, Green D, Taal M, Whetton TD, Kalra PA
Biomark Insights
· 2020 · PMID 33311975
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Biomarker discovery in the field of risk prediction in chronic kidney disease (CKD) embraces the prospect of improving our ability to risk stratify future adverse outcomes and thereby guide patient care in a new era of p...Biomarker discovery in the field of risk prediction in chronic kidney disease (CKD) embraces the prospect of improving our ability to risk stratify future adverse outcomes and thereby guide patient care in a new era of personalised medicine. However, many studies that report biomarkers predictive of CKD progression share a key methodological limitation: failure to characterise patients' renal progression precisely. This weakens any observable association between a biomarker and an outcome poorly defined by a patient's change in renal function over time. In this commentary, we discuss the need for a better approach in this research arena and describe a compelling strategy that has the advantage of offering robust and meaningful biomarker exploration relevant to CKD progression.
Biomark Insights
· 2020 · PMID 33293784
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Over the last decade, biomarkers have significantly improved our understanding of the pathophysiology of Alzheimer disease (AD) and provided valuable tools to examine different disease mechanisms and their progression ov...Over the last decade, biomarkers have significantly improved our understanding of the pathophysiology of Alzheimer disease (AD) and provided valuable tools to examine different disease mechanisms and their progression over time. While several markers of amyloid, tau, neuronal, synaptic, and axonal injury, inflammation, and immune dysregulation in AD have been identified, there is a relative paucity of biomarkers which reflect other disease mechanisms such as oxidative stress, mitochondrial injury, vascular or endothelial injury, and calcium-mediated excitotoxicity. Importantly, there is an urgent need to standardize methods for biomarker assessments across different centers, and to identify dynamic biomarkers which can monitor disease progression over time and/or response to potential disease-modifying treatments. The updated research framework for AD, proposed by the National Institute of Aging- Alzheimer's Association (NIA-AA) Work Group, emphasizes the importance of incorporating biomarkers in AD research and defines AD as a biological construct consisting of amyloid, tau, and neurodegeneration which spans pre-symptomatic and symptomatic stages. As results of clinical trials of AD therapeutics have been disappointing, it has become increasingly clear that the success of future AD trials will require the incorporation of biomarkers in participant selection, prognostication, monitoring disease progression, and assessing response to treatments. We here review the current state of fluid AD biomarkers, and discuss the advantages and limitations of the updated NIA-AA research framework. Importantly, the integration of biomarker data with clinical, cognitive, and imaging domains through a systems biology approach will be essential to adequately capture the molecular, genetic, and pathological heterogeneity of AD and its spatiotemporal evolution over time.
Biomark Insights
· 2020 · PMID 33192050
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Biomarkers are critical tools that underpin precision medicine. However there has been slow progress and frequent failure of biomarker development. The root causes are multifactorial. Here, we focus on the need for fast,...Biomarkers are critical tools that underpin precision medicine. However there has been slow progress and frequent failure of biomarker development. The root causes are multifactorial. Here, we focus on the need for fast, efficient, and reliable access to quality biospecimens as a critical area that impacts biomarker development. We discuss the past history of biobanking and the evolution of biobanking processes relevant to the specific area of cancer biomarker development as an example, and describe some solutions that can improve this area, thus potentially accelerating biomarker research.
Biomark Insights
· 2020 · PMID 33110346
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Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; yet, obesity also inde...Over 35% of the adult US population is obese. In turn, excess adiposity increases the risk of multiple complications including type 2 diabetes (T2D), insulin resistance, and cardiovascular disease; yet, obesity also independently heightens risk of Alzheimer's Disease (AD), even after adjusting for other important confounding risk factors including blood pressure, sociodemographics, cholesterol levels, smoking status, and Apolipoprotein E (ApoE) genotype. Among patients over the age of 65 with dementia, 37% have coexisting diabetes, and an estimated 7.3% of cases of AD are directly attributable to midlife obesity. Clusterin, also known as apolipoprotein J (ApoJ), is a multifunctional glycoprotein that acts as a molecular chaperone, assisting folding of secreted proteins. Clusterin has been implicated in several physiological and pathological states, including AD, metabolic disease, and cardiovascular disease. Despite long-standing interest in elucidating clusterin's relationship with amyloid beta (Aβ) aggregation/clearance and toxicity, significant knowledge gaps still exist. Altered clusterin expression and protein levels have been linked with cognitive and memory function, disrupted central nervous system lipid flux, as well as pathogenic brain structure; and its role in cardiometabolic disease suggests that it may be a link between insulin resistance, dyslipidemia, and AD. Here, we briefly highlight clusterin's relevance to AD by presenting existing evidence linking clusterin to AD and cardiometabolic disease, and discussing its potential utility as a biomarker for AD in the presence of obesity-related metabolic disease.
Farotti L, Paolini Paoletti F, Simoni S
… +1 more, Parnetti L
Biomark Insights
· 2020 · PMID 33110345
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Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis an...Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow for early and more precise diagnosis and provide information about prognosis. Developments in analytical chemistry allow for the detection of a large number of molecules in cerebrospinal fluid (CSF), which are known to be associated with the pathogenesis of PD. Given the pathophysiology of PD, CSF α-synuclein species have the strongest rationale for use, also providing encouraging preliminary results in terms of early diagnosis. In the field of classical Alzheimer's disease (AD) biomarkers, low CSF Aβ levels have shown a robust prognostic value in terms of development of cognitive impairment. Other CSF biomarkers including lysosomal enzymes, neurofilament light chain, markers of neuroinflammation and oxidative stress, although promising, have not proved to be reliable for diagnostic and prognostic purposes yet. Overall, the implementation of CSF biomarkers may give a substantial contribution to the optimal use of disease-modifying drugs.
Álvarez-Rodríguez II, Castaño-Tostado E, García-Gutiérrez DG
… +4 more, Reynoso-Camacho R, Elton-Puente JE, Barajas-Pozos A, Pérez-Ramírez IF
Biomark Insights
· 2020 · PMID 32952396
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Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to...Diabetic foot ulcer (DFU) is a common complication of type 2 diabetes mellitus (T2DM) characterized by ulcer formation, which can lead to the amputation of lower extremities. However, the metabolic alterations related to this complication are not completely elucidated. Therefore, we carried out a metabolomic analysis of serum samples obtained from T2DM adult patients diagnosed with diabetic foot ulcer in a cross-sectional, observational, and comparative study. Eighty-four volunteers were classified into the following groups: without T2DM (control group, n = 30) and with T2DM and different stages of diabetic foot ulcer according to Wagner-Meggitt classification system: DFU G0 (n = 11), DFU G1 (n = 14), DFU G2 (n = 16), and DFU G3 (n = 13). The non-target metabolomic profile followed by chemometric analysis revealed that lysophosphatidylethanolamine (16:1) could be proposed as key metabolite related to the onset of diabetic foot ulcer; however, this phospholipid was not affected by diabetic foot ulcer progression. Therefore, further studies are necessary to validate these phospholipids as biomarker candidates for the early diagnosis of diabetic foot ulcer in T2DM patients.
Camporesi E, Nilsson J, Brinkmalm A
… +4 more, Becker B, Ashton NJ, Blennow K, Zetterberg H
Biomark Insights
· 2020 · PMID 32913390
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Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders...Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer's disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.
Biomark Insights
· 2020 · PMID 32821082
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We review simple methods for evaluating 4 types of biomarkers. First, we discuss the evaluation of surrogate endpoint biomarkers (to shorten a randomized trial) using 2 statistical and 3 biological criteria. Second, we d...We review simple methods for evaluating 4 types of biomarkers. First, we discuss the evaluation of surrogate endpoint biomarkers (to shorten a randomized trial) using 2 statistical and 3 biological criteria. Second, we discuss the evaluation of prognostic biomarkers (to predict the risk of disease) by comparing data collection costs with the anticipated net benefit of risk prediction. Third, we discuss the evaluation of predictive markers (to search for a promising subgroup in a randomized trial) using a multivariate subpopulation treatment effect pattern plot involving a risk difference or responders-only benefit function. Fourth, we discuss the evaluation of cancer screening biomarkers (to predict cancer in asymptomatic persons) using methodology to substantially reduce the sample size with stored specimens.
Salao K, Sawanyawisuth K, Winaikosol K
… +2 more, Choonhakarn C, Chaowattanapanit S
Biomark Insights
· 2020 · PMID 32684747
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Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate th...Chronic pruritus of unknown origin (CPUO) is a refractory condition. The expression of Interleukin-31 (IL-31), a major pruritogenic cytokine, in CPUO patients has not been investigated. This study aimed to investigate the potential association of IL-31 with CPUO. This was a cross-sectional, analytical study. Patients diagnosed with CPUO and healthy subjects were included at a ratio of 1:2. Serum IL-31 levels were measured in both groups and compared. There were 10 CPUO and 20 healthy subjects who participated in this study. The median IL-31 level in the CPUO group was significantly higher than in the healthy group (127.3 vs 34.4 pg/mL; < .001). The presence of CPUO was independently associated with IL-31 levels with a coefficient of 89.678 ( < .001). The serum IL-31 cutoff point for CPUO was 56.8 pg/mL, with an area under the receiver operating characteristic curve (ROC) of 100%. Chronic pruritus of unknown origin was significantly and independently associated with higher IL-31 levels. Further clinical trials of IL-31-related treatment may be justified in CPUO patients.
Biomark Insights
· 2020 · PMID 32550766
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BACKGROUND: Human saliva has been identified as a novel, practical, and noninvasive source of biomarkers and genetic materials. However, it is equally challenging due to the availability of an abundance of impurities in...BACKGROUND: Human saliva has been identified as a novel, practical, and noninvasive source of biomarkers and genetic materials. However, it is equally challenging due to the availability of an abundance of impurities in the form of microbes and other proteinaceous compounds. The objective of this study was to develop a robust, reproducible, and economic method of extracting high-yield and high-quality RNA from whole human saliva. METHODS: The modified TRIzol protocol was developed to extract RNA from saliva (n = 14), followed by complementary DNA synthesis and reverse transcription quantitative polymerase chain reaction analyses for the genes encoding , and To compare our protocol with the spin column-based method, we used Qiagen Salivary Protect Micro-RNA spin columns (n = 6). To evaluate and compare the yields and quality of extracted RNAs from both methods, we used (1) Experion Bioanalyzer, (2) QuantiFluor RNA dye, and (3) NanoDrop 2000 Spectrometer. RESULTS: With the modified TRIzol lysis protocol, a high yield of total RNA, on average 12.34 μg, from saliva was extracted compared with on average 0.2 μg with a spin column-based method. The average RQI (RNA quality index) with the TRIzol method was 7.86, which is also comparable with that of the spin column-based method (RQI = 7.58). QuantiFluor dye used for RNA quantification showed a 16-fold higher yield of RNA concentration using our TRIzol protocol. CONCLUSIONS: Our modified TRIzol protocol is a reproducible method to extract RNA from whole human saliva which can be used for gene expression analysis. This method allows also ensures the quality of RNA required for specific applications such as RNA sequencing.
Veiga L, Brito M, Silva C
… +1 more, Silva-Nunes J
Biomark Insights
· 2020 · PMID 32550765
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INTRODUCTION: Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated to an insulin sensitizing action and to a negative act...INTRODUCTION: Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated to an insulin sensitizing action and to a negative action on energy balance. The aim of this study was to analyze the association between the serum levels of UAG and glucose metabolism parameters in obese women, independently from eventual influence of anthropometrics. METHODS: One hundred lean and 254 obese Caucasian women were studied. Each woman was characterized for anthropometrics, fasting glucose, insulin, HbA1c, and UAG. In addition, obese women were subjected to a classic oral glucose tolerance test (oGTT) to assess glucose and insulin at 120 minutes. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR). Obese women were classified in 3 glycemic status subgroups (normoglycemia, prediabetes, and diabetes) according to HbA1c and to fasting and oGTT glucose values. RESULTS: In comparison with the lean group, significantly lower levels of UAG were observed in obese women. However, no significant difference was observed through obesity classes I to III. UAG levels were not significantly different among glycemic status subgroups and did not show any association with glucose, insulin, HOMA-IR, or HbA1c. CONCLUSIONS: Although anthropometry can influence the level of the unacylated form of ghrelin, UAG plasma levels do not associate to glucose homeostasis parameters.
Durrance RJ, Ullah T, Patel H
… +5 more, Martinez G, Cervellione K, Zafonte VB, Gafoor K, Bagheri F
Biomark Insights
· 2020 · PMID 32476970
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BACKGROUND: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of diseas...BACKGROUND: Bacteremia and sepsis are significant contributors to the morbidity, mortality, and economic burden of health care systems worldwide. Procalcitonin has been identified as a potentially useful marker of disease and severity in sepsis. However, the assumption that greater procalcitonin levels correlate with greater burden of disease has not been adequately studied. METHODS: A retrospective chart review of adult patients admitted to an urban teaching hospital with suspected sepsis was undertaken to test the association of elevated procalcitonin (>30 ng/mL) with other markers of sepsis (lactic acid, white blood cell count, percent bands), severity of disease (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation-II [APACHE II] scores), and mortality. RESULTS: In total, 168 patients were identified over 18 months (42% ward, 11% Stepdown, 44% medical intensive care unit [MICU], 2% surgical intensive care unit (STICU), 1% gynecology [GYN]). The Spearman correlation analysis showed that serum procalcitonin level did not correlate with SOFA ( = .238) or APACHE II ( = .918) scores on admission, and did not correlate with survival (Kruskal-Wallis test, = .937). However, higher serum procalcitonin levels were associated with patients who had positive blood cultures (Kruskal-Wallis test, = .0016 for Gram-positive and = .0007 for Gram-negative bacteria). Lactic acid levels on admission strongly correlated with SOFA APACHE II (the Spearman correlation, < .0001 for both) and mortality ( = .0001 for both). CONCLUSIONS: Higher serum procalcitonin levels above 30 ng/mL failed to correlate with indicators of sepsis, severity of disease (SOFA and APACHE II scores), and mortality but were associated with positive blood cultures. Lactic acid levels did show correlation to both severity of disease and mortality. Serum procalcitonin levels >30 ng/mL do not appear to correlate with the severity of disease in a sample of patients with markedly elevated initial procalcitonin levels.
Edes AN, Edwards KL, Wolfe BA
… +2 more, Brown JL, Crews DE
Biomark Insights
· 2020 · PMID 32425494
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Allostatic load, or the physiological dysregulation accumulated due to senescence and stress, is an established predictor of human morbidity and mortality and has been proposed as a tool for monitoring health and welfare...Allostatic load, or the physiological dysregulation accumulated due to senescence and stress, is an established predictor of human morbidity and mortality and has been proposed as a tool for monitoring health and welfare in captive wildlife. It is estimated by combining biomarkers from multiple somatic systems into allostatic load indices (ALIs), providing a score representing overall physiological dysregulation. Such ALIs have been shown to predict disease and mortality risk in western lowland gorillas. In these prior analyses, we were unable to include lipid markers, a potential limitation as they are key biomarkers in human models. Recently, we were able to assay serum cholesterol and triglycerides and add them to our previous ALI. We then re-examined associations with health outcomes using binomial generalized linear models. We constructed ALIs using 2 pooling strategies and 2 methods. By itself, a 1-unit increase in allostatic load was associated with higher odds of all-cause morbidity and mortality, but results were mixed for cardiac disease. However, the best fit models for all-cause morbidity and cardiac disease included only age and sex. Allostatic load was retained alongside age in the best fit models for mortality, with a 1-unit increase associated with 23% to 45% higher odds of death. Compared with previous results, ALIs containing cholesterol and triglycerides better predict disease risk in zoo-housed western lowland gorillas, as evidenced by larger effect sizes for some models and better goodness of fit for all ALIs. Based on these results, we address methodology for future allostatic load research on wildlife.
Dominguez GA, Polo AT, Roop J
… +5 more, Campisi AJ, Somer RA, Perzin AD, Gabrilovich DI, Kumar A
Biomark Insights
· 2020 · PMID 32341637
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Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection m...Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status, thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy test that uses flow cytometry-based immunophenotyping and artificial neural network (ANN) analysis to detect PCa. Numerous myeloid and lymphoid cell populations, including myeloid-derived suppressor cells, were measured from 156 patients with PCa, 123 with benign prostatic hyperplasia (BPH), and 99 male healthy donor (HD) controls. Using pattern recognition neural network (PRNN) analysis, a type of ANN, PCa detection compared against HD resulted in 96.6% sensitivity, 87.5% specificity, and an area under the curve (AUC) value of 0.97. Detecting patients with higher risk disease (⩾Gleason 7) against lower risk disease (BPH/Gleason 6) resulted in 92.0% sensitivity, 42.7% specificity, and an AUC of 0.72. This study suggests that analyzing flow cytometry immunophenotyping data with PRNNs may prove to be a useful tool to improve PCa detection and reduce the number of unnecessary prostate biopsies performed each year.
Biomark Insights
· 2020 · PMID 32313424
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This editorial announces the new Biomarker Insights Editor-in-Chief. The journal will continue to publish high-quality original reports and review articles in all areas of biomarker research, and will welcome submissions...This editorial announces the new Biomarker Insights Editor-in-Chief. The journal will continue to publish high-quality original reports and review articles in all areas of biomarker research, and will welcome submissions that focus on improving the quality of the biomarker research literature.
Huraib GB, Al Harthi F, Arfin M
… +3 more, Aljamal A, Alrawi AS, Al-Asmari A
Biomark Insights
· 2020 · PMID 32076368
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The is associated with susceptibility to autoimmune diseases. The functional polymorphism in at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Pr...The is associated with susceptibility to autoimmune diseases. The functional polymorphism in at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls ( < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.
Piccardi B, Biagini S, Iovene V
… +1 more, Palumbo V
Biomark Insights
· 2019 · PMID 31903021
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PURPOSE: Postischemic reperfusion injury may exacerbate cerebral damage and capillary dysfunction, leading to brain edema (BE), hemorrhagic transformation (HT), necrosis, and injury from free radicals with subsequent inf...PURPOSE: Postischemic reperfusion injury may exacerbate cerebral damage and capillary dysfunction, leading to brain edema (BE), hemorrhagic transformation (HT), necrosis, and injury from free radicals with subsequent infarct growth (IG). Several plasmatic biomarkers involved in the ischemic cascade have been studied in relation to radiological and clinical outcomes of reperfusion injury in ischemic stroke with heterogeneous results. This article provides a brief overview of the contribution of circulating biomarkers to the pathophysiology of parenchymal damage in ischemic stroke patients treated with revascularization therapies. METHODS: We included full reports with measurements of plasma markers in patients with acute ischemic stroke treated with revascularization therapies. FINDINGS: Our research included a large number of observational studies investigating a possible role of circulating biomarkers in the development of parenchymal damage after acute stroke treatments. To make the results clearer, we divided the review in 4 sections, exploring the relation of different biomarkers with each of the indicators of parenchymal damage (HT, BE, IG, recanalization). DISCUSSION AND CONCLUSION: Definite conclusions are difficult to draw because of heterogeneity across studies. However, our review seems to confirm an association between some circulating biomarkers (particularly matrix metalloproteinase-9) and occurrence of parenchymal damage in ischemic stroke patients treated with revascularization therapies.
Yousefi Z, Sharifzadeh S, Yar-Ahmadi V
… +2 more, Andalib A, Eskandari N
Biomark Insights
· 2019 · PMID 31798301
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BACKGROUND: Human B-cell responses are regulated through synergy between a collection of activation and inhibitory receptors. Fc receptor-like (FCRL) molecules have recently been identified as co-receptors that are prefe...BACKGROUND: Human B-cell responses are regulated through synergy between a collection of activation and inhibitory receptors. Fc receptor-like (FCRL) molecules have recently been identified as co-receptors that are preferentially expressed in human B-cells, which may also play an important role in the regulation of human B-cell responses. FCRL1 is a member of the FCRL family molecules with 2 immunoreceptor tyrosine-based activation motifs (ITAMs) in its cytoplasmic tail. This study aimed to investigate the regulatory roles of FCRL1 in human B-cell responses. MATERIALS AND METHODS: The regulatory potential of FCRL1 in human B-cell through knockdown of FCRL1 expression in the Ramos and Daudi Burkitt lymphoma (BL) cell lines by using the retroviral-based short hairpin ribonucleic acid (shRNA) delivery method. The functional consequences of FCRL1 knockdown were assessed by measuring the proliferation, apoptosis, and the expression levels of , and genes as well as phosphoinositide-3 kinase/-serine-threonine kinase AKT (PI3K/p-AKT) pathway in the BL cells, using the quantitative real-time polymerase chain reaction (PCR) and flow cytometry analysis. The NF-κB activity was also measured by the enzyme-linked immunosorbent assay (ELISA). RESULTS: FCRL1 knockdown significantly decreased cell proliferation and increased apoptotic cell death in the BL cells. There was a significant reduction in the extent of the gene expression in the treated BL cells compared with control cells. On the contrary, FCRL1 knockdown increased the expression levels of and genes in the treated BL cells when compared with control cells. In addition, the extent of the PI3K/p-AKT expression and phosphorylated-p65 NF-κB activity was significantly decreased in the treated BL cells compared with control cells. CONCLUSIONS: These results suggest that FCRL1 can play a key role in the activation of human B-cell responses and has the potential to serve as a target for immunotherapy of FCRL1 positive B-cell-related disorders.