Potential of Point-of-Care and At-Home Assessment of Immune Status via Rapid Cytokine Detection and Questionnaire-Based Anamnesis

Monitoring the immune system’s status has emerged as an urgent demand in critical health conditions. The circulating cytokine levels in the blood reflect a thorough insight into the immune system status. Indeed, measuring one cytokine may deliver more information equivalent to detecting multiple diseases at a time. However, if the reported cytokine levels are interpreted with considering lifestyle and any comorbid health conditions for the individual, this will promote a more precise assessment of the immune status. Therefore, this study addresses the most recent advanced assays that deliver rapid, accurate measuring of the cytokine levels in human blood, focusing on add-on potentials for point-of-care (PoC) or personal at-home usage, and investigates existing health questionnaires as supportive assessment tools that collect all necessary information for the concrete analysis of the measured cytokine levels. We introduced a ten-dimensional featuring of cytokine measurement assays. We found 15 rapid cytokine assays with assay time less than 1 h; some could operate on unprocessed blood samples, while others are mature commercial products available in the market. In addition, we retrieved several health questionnaires that addressed various health conditions such as chronic diseases and psychological issues. Then, we present a machine learning-based solution to determine what makes the immune system fit. To this end, we discuss how to employ topic modeling for deriving the definition of immune fitness automatically from literature. Finally, we propose a prototype model to assess the fitness of the immune system through leveraging the derived definition of the immune fitness, the cytokine measurements delivered by a rapid PoC immunoassay, and the complementary information collected by the health questionnaire about other health factors. In conclusion, we discovered various advanced rapid cytokine detection technologies that are promising candidates for point-of-care or at-home usage; if paired with a health status questionnaire, the assessment of the immune system status becomes solid and we demonstrated potentials for promoting the assessment tool with data mining techniques.

[1]  K. Asadullah,et al.  Interleukin (IL)‐19, IL‐20 and IL‐24 are produced by and act on keratinocytes and are distinct from classical ILs , 2006, Experimental dermatology.

[2]  L. Arendt-Nielsen,et al.  Serum Levels of Proinflammatory Cytokines in Painful Knee Osteoarthritis and Sensitization , 2015, International journal of inflammation.

[3]  K. Chung,et al.  Cytokines in chronic obstructive pulmonary disease , 2001, European Respiratory Journal.

[4]  Dan Wu,et al.  Sequentially multiplexed amperometry for electrochemical biosensors. , 2018, Biosensors & bioelectronics.

[5]  B. Cislaghi,et al.  Self-rated health as a valid indicator for health-equity analyses: evidence from the Italian health interview survey , 2019, BMC Public Health.

[6]  G. Nageswaran,et al.  Plasma Modified Polymeric Materials for Biosensors/Biodevice Applications , 2019, Non-Thermal Plasma Technology for Polymeric Materials.

[7]  Derek Greene,et al.  How Many Topics? Stability Analysis for Topic Models , 2014, ECML/PKDD.

[8]  Bruce W. Smith,et al.  The brief resilience scale: Assessing the ability to bounce back , 2008, International journal of behavioral medicine.

[9]  M. Ellmerer,et al.  Development and validation of a low cost blood filtration element separating plasma from undiluted whole blood. , 2012, Biomicrofluidics.

[10]  Hyunsoo Kim,et al.  Sparse Non-negative Matrix Factorizations via Alternating Non-negativity-constrained Least Squares , 2006 .

[11]  W. Rief,et al.  Psychobiological aspects of somatization syndromes: Contributions of inflammatory cytokines and neopterin , 2012, Psychiatry Research.

[12]  A Point of Care Lateral Flow Assay for Rapid and Colorimetric Detection of Interleukin 6 and Perspectives in Bedside Diagnostics , 2020 .

[13]  A. Daniilidis,et al.  Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study , 2016, Acta Cytologica.

[14]  Munezza Ata Khan,et al.  Recent Advances in Electrochemical and Optical Biosensors Designed for Detection of Interleukin 6 , 2020, Sensors.

[15]  P. Reed,et al.  Problematic Internet Usage and Immune Function , 2015, PloS one.

[16]  Keith Sigel,et al.  An inflammatory cytokine signature predicts COVID-19 severity and survival , 2020, Nature Medicine.

[17]  M. Rajappa,et al.  Role of Pro-/Anti-Inflammatory Cytokines and Their Correlation With Established Risk Factors in South Indians With Coronary Artery Disease , 2009, Angiology.

[18]  Laura Anfossi,et al.  Multiplex Lateral Flow Immunoassay: An Overview of Strategies towards High-throughput Point-of-Need Testing , 2018, Biosensors.

[19]  M. Lekander,et al.  A global measure of sickness behaviour: Development of the Sickness Questionnaire , 2018, Journal of health psychology.

[20]  A. Descoteaux,et al.  Macrophage Cytokines: Involvement in Immunity and Infectious Diseases , 2014, Front. Immunol..

[21]  S. Sell,et al.  How the immune system works. , 1980, Medical times.

[22]  Michael I. Jordan,et al.  Latent Dirichlet Allocation , 2001, J. Mach. Learn. Res..

[23]  Mohammad Zarei,et al.  Portable biosensing devices for point-of-care diagnostics: Recent developments and applications , 2017 .

[24]  R. Srivastava,et al.  Fluorescence lateral flow immunoassay based point-of-care nanodiagnostics for orthopedic implant-associated infection , 2019, Sensors and Actuators B: Chemical.

[25]  T. Noah,et al.  Chemokines in nasal secretions of normal adults experimentally infected with respiratory syncytial virus. , 2000, Clinical immunology.

[26]  N. Ohkohchi,et al.  Photonic Lab-on-a-Chip for Rapid Cytokine Detection , 2016 .

[27]  Jongmin Park,et al.  Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. , 2018, ACS nano.

[28]  I. el-Kady,et al.  Pro-inflammatory and anti-inflammatory cytokines profile in rheumatoid arthritis patients. , 2008, The Egyptian journal of immunology.

[29]  Ayden Malekjahani,et al.  Engineering Steps for Mobile Point-of-Care Diagnostic Devices. , 2019, Accounts of chemical research.

[30]  Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections , 2021, Nature communications.

[31]  N. Roxhed,et al.  High-Yield Passive Plasma Filtration from Human Finger Prick Blood. , 2018, Analytical chemistry.

[32]  A. Leite-Moreira,et al.  Automatic text-mining as an unbiased approach to uncover molecular associations between periodontitis and coronary artery disease , 2021, Biomarkers.

[33]  Hans-Peter Deigner,et al.  A smartphone readout system for gold nanoparticle-based lateral flow assays: application to monitoring of digoxigenin , 2019, Microchimica Acta.

[34]  S. Cathcart,et al.  Peripheral interleukin-1ß levels are elevated in chronic tension-type headache patients. , 2013, Pain research & management.

[35]  Michael E. Hall,et al.  Exogenous CXCL4 infusion inhibits macrophage phagocytosis by limiting CD36 signalling to enhance post-myocardial infarction cardiac dilation and mortality , 2018, Cardiovascular research.

[36]  R. Krawetz,et al.  Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain , 2018, BMC Musculoskeletal Disorders.

[37]  Gregg Pratt,et al.  DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration , 1998 .

[38]  H. Hoogsteden,et al.  Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia , 2012, European Respiratory Journal.

[39]  D. Goldberg,et al.  A scaled version of the General Health Questionnaire , 1979, Psychological Medicine.

[40]  B. Lüscher,et al.  Cytokines and the Skin Barrier , 2013, International journal of molecular sciences.

[41]  Charles Møller,et al.  Smart literature review: a practical topic modelling approach to exploratory literature review , 2019, Journal of Big Data.

[42]  A. Undén,et al.  Self-rated health. Comparisons between three different measures. Results from a population study. , 2001, International journal of epidemiology.

[43]  Shivangi Sachdeva,et al.  Microfluidic Point-of-Care Testing: Commercial Landscape and Future Directions , 2021, Frontiers in Bioengineering and Biotechnology.

[44]  H. Young,et al.  Adaptive in vivo device for theranostics of inflammation: real-time monitoring of interferon-γ and aspirin. , 2020, Acta biomaterialia.

[45]  Ana I. Barbosa,et al.  Multiplexed femtomolar quantitation of human cytokines in a fluoropolymer microcapillary film. , 2015, The Analyst.

[46]  Nae-Eung Lee,et al.  Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing. , 2020, Chemical Society reviews.

[47]  Balwinder Kaur,et al.  From Point-of-Care Testing to eHealth Diagnostic Devices (eDiagnostics) , 2018, ACS central science.

[48]  Toshio Tanaka,et al.  IL-6 in inflammation, immunity, and disease. , 2014, Cold Spring Harbor perspectives in biology.

[49]  Haley Marks,et al.  Surface enhanced Raman spectroscopy (SERS) for in vitro diagnostic testing at the point of care , 2017 .

[50]  Barbara Kitchenham,et al.  Procedures for Performing Systematic Reviews , 2004 .

[51]  S. Rana,et al.  Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant irritable bowel syndrome patients. , 2012, Tropical gastroenterology : official journal of the Digestive Diseases Foundation.

[52]  Hanmei Xu,et al.  Tumor-related interleukins: old validated targets for new anti-cancer drug development , 2017, Molecular Cancer.

[53]  C. Albanesi,et al.  Interleukin-17 is produced by both Th1 and Th2 lymphocytes, and modulates interferon-gamma- and interleukin-4-induced activation of human keratinocytes. , 2000, The Journal of investigative dermatology.

[54]  K. Devriendt,et al.  Enhanced MCP-1 Release in Early Autosomal Dominant Polycystic Kidney Disease , 2021, Kidney international reports.

[55]  B. Norton.  Immunological methods , 1995, Nature.

[56]  Jo Woon Chong,et al.  Analyte Quantity Detection from Lateral Flow Assay Using a Smartphone , 2019, Sensors.

[57]  M. Richetta,et al.  Development of a Smartphone Based Reader for the Quantitative Analysis of Lateral Flow Assays , 2018, Materials Science Forum.

[58]  Sungha Park,et al.  Serum cytokine profiles in healthy young and elderly population assessed using multiplexed bead-based immunoassays , 2011, Journal of Translational Medicine.

[59]  A. Scholey,et al.  Development and Validation of the Immune Status Questionnaire (ISQ) , 2019, International journal of environmental research and public health.

[60]  C. Costea,et al.  Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker? , 2019, International journal of hypertension.

[61]  K. Asadullah,et al.  IL-22 increases the innate immunity of tissues. , 2004, Immunity.

[62]  S. R. Golish,et al.  Cytokine evaluation in individuals with low back pain using discographic lavage. , 2010, The spine journal : official journal of the North American Spine Society.

[63]  X. Zhang,et al.  Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology , 2002, Schizophrenia Research.

[64]  B. Andryukov.  Six decades of lateral flow immunoassay: from determining metabolic markers to diagnosing COVID-19 , 2020, AIMS microbiology.

[65]  Ashok Kumar,et al.  The IL-12 family of cytokines in infection, inflammation and autoimmune disorders. , 2009, Inflammation & allergy drug targets.

[66]  Santimukul Santra,et al.  A Comparison of Optical, Electrochemical, Magnetic, and Colorimetric Point-of-Care Biosensors for Infectious Disease Diagnosis. , 2018, ACS infectious diseases.

[67]  H. Hammad,et al.  The Cytokines of Asthma. , 2019, Immunity.

[68]  S. Fischer,et al.  Development of an IL-6 point-of-care assay: utility for real-time monitoring and management of cytokine release syndrome and sepsis. , 2019, Bioanalysis.

[69]  O. Vittecoq,et al.  Rheumatoid arthritis, insulin resistance, and diabetes. , 2017, Joint, bone, spine : revue du rhumatisme.

[70]  J. Alcocer-Varela,et al.  Cytokine gene expression in cirrhotic and non-cirrhotic human liver. , 1996, Journal of hepatology.

[71]  Jaegul Choo,et al.  Nonnegative Matrix Factorization for Interactive Topic Modeling and Document Clustering , 2014 .

[72]  Taif Alawsi,et al.  A review of smartphone point‐of‐care adapter design , 2019, Engineering Reports.

[73]  Jianping Fu,et al.  Supplementary Information for Multiplex Serum Cytokine Immunoassay Using Nanoplasmonic Biosensor Microarrays , 2015 .

[74]  C. Bachert,et al.  Elevated levels of interleukins IL-1β, IL-6 and IL-8 in naturally acquired viral rhinitis , 2006, European Archives of Oto-Rhino-Laryngology.

[75]  K. Kedzierska,et al.  Cytokines and HIV-1: Interactions and Clinical Implications , 2001, Antiviral chemistry & chemotherapy.

[76]  Tassaneewan Laksanasopin,et al.  Point-of-Care Diagnostics: Recent Developments in a Connected Age. , 2017, Analytical chemistry.

[77]  Shana O Kelley,et al.  Electrochemical DNA-Based Immunoassay That Employs Steric Hindrance To Detect Small Molecules Directly in Whole Blood. , 2017, ACS sensors.

[78]  P. Pynsent,et al.  The Oswestry Disability Index. , 2000, Spine.

[79]  Cui Tao,et al.  Systematic identification of latent disease-gene associations from PubMed articles , 2018, PloS one.

[80]  Weiqiang Chen,et al.  Magnet Patterned Superparamagnetic Fe3O4/Au Core–Shell Nanoplasmonic Sensing Array for Label‐Free High Throughput Cytokine Immunoassay , 2019, Advanced healthcare materials.

[81]  A. Scholey,et al.  Perceived Immune Fitness, Individual Strength and Hangover Severity , 2020, International journal of environmental research and public health.

[82]  H. Schellekens,et al.  Cytokines and the immune response , 1996, Biotherapy.

[83]  D. Lawrence,et al.  Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection , 2013, Mediators of inflammation.

[84]  L. Hansson,et al.  Self-rated Health Is Related to Levels of Circulating Cytokines , 2004, Psychosomatic medicine.

[85]  J. Rusling,et al.  High-Throughput Electrochemical Microfluidic Immunoarray for Multiplexed Detection of Cancer Biomarker Proteins. , 2016, ACS sensors.

[86]  J. Navarro-González,et al.  The role of inflammatory cytokines in diabetic nephropathy. , 2008, Journal of the American Society of Nephrology : JASN.

[87]  Ralf Junker,et al.  Recent advances in immunodiagnostics based on biosensor technologies—from central laboratory to the point of care , 2019, Analytical and Bioanalytical Chemistry.

[88]  F. Cardoso,et al.  Lab-on-Chip Devices: Gaining Ground Losing Size. , 2017, ACS nano.

[89]  L. Shcherbakova,et al.  The Blood Cytokine Profile of Young People with Early Ischemic Heart Disease Comorbid with Abdominal Obesity , 2020, Journal of personalized medicine.

[90]  H. Parkman,et al.  Rome IV Diagnostic Questionnaire Complements Patient Assessment of Gastrointestinal Symptoms for Patients with Gastroparesis Symptoms , 2018, Digestive Diseases and Sciences.

[91]  P. Schulte,et al.  Evaluation of immune responses. , 2011, IARC scientific publications.

[92]  J. Krueger.  The role of cytokines in sleep regulation. , 2008, Current pharmaceutical design.

[93]  Saleh M. Ibrahim,et al.  Cytokines and Cytokine Profiles in Human Autoimmune Diseases and Animal Models of Autoimmunity , 2009, Mediators of inflammation.

[94]  B. Topçu,et al.  Relationship among MIF, MCP-1, viral loads, and HBs Ag levels in chronic hepatitis B patients. , 2015, Turkish journal of medical sciences.

[95]  Xiaogan Liang,et al.  Biotunable Nanoplasmonic Filter on Few-Layer MoS2 for Rapid and Highly Sensitive Cytokine Optoelectronic Immunosensing. , 2017, ACS nano.

[96]  G. López-Castejón,et al.  Understanding the mechanism of IL-1β secretion , 2011, Cytokine & growth factor reviews.

[97]  R. Shephard,et al.  The Cytokine Response to Physical Activity and Training , 2001, Sports medicine.

[98]  R. Whitehead,et al.  The Assessment of Immune Status , 1976 .

[99]  R. Elashoff,et al.  Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease , 2016, Arthritis Research & Therapy.

[100]  Fernando A Bozza,et al.  Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis , 2007, Critical care.

[101]  K. Reinhart,et al.  Rapid diagnosis of sepsis , 2013, Virulence.

[102]  Xinwen Zhou,et al.  The dual roles of cytokines in Alzheimer’s disease: update on interleukins, TNF-α, TGF-β and IFN-γ , 2016, Translational Neurodegeneration.

[103]  J. Verster,et al.  Mental resilience, perceived immune functioning, and health , 2017, Journal of multidisciplinary healthcare.

[104]  T. Pincus,et al.  Inflammation-associated insulin resistance: differential effects in rheumatoid arthritis and systemic lupus erythematosus define potential mechanisms. , 2008, Arthritis and rheumatism.

[105]  R. Pioli,et al.  The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6 , 1998, Schizophrenia Research.

[106]  Roberto de la Rica,et al.  Nanoparticle-based mobile biosensors for the rapid detection of sepsis biomarkers in whole blood , 2020, Nanoscale advances.

[107]  N. Duggal.  Reversing the immune ageing clock: lifestyle modifications and pharmacological interventions , 2018, Biogerontology.

[108]  Qinqin Meng,et al.  A Single-Item Self-Rated Health Measure Correlates with Objective Health Status in the Elderly: A Survey in Suburban Beijing , 2014, Front. Public Health.

[109]  Jasmina Casals-Terré,et al.  Self-driven filter-based blood plasma separator microfluidic chip for point-of-care testing , 2015, Biofabrication.

[110]  Qin Xiao,et al.  Research progress on chemiluminescence immunoassay combined with novel technologies , 2020 .

[111]  Guangfu Yang,et al.  Recent advances in cytokine detection by immunosensing. , 2016, Biosensors & bioelectronics.

[112]  W. Vach,et al.  Construction and Clinical Validation of a Questionnaire-based Risk Score to Identify Patients Suffering from Immunodeficiency or Systemic Autoimmunity , 2014 .