Why current quantitative serology is not quantitative and how systems immunology could provide solutions

Biologia Futura - Tập 72 Số 1 - Trang 37-44 - 2021
József Prechl1
1R&D Laboratory, Diagnosticum Zrt., Attila út 126, Budapest, 1047, Hungary

Tóm tắt

AbstractDetermination of the presence of antibodies against infectious agents, self-antigens, allogeneic antigens and environmental antigens is the goal of medical serology. Along with the standardization of these tests the community also started to use the expression “quantitative serology,” referring to the fact that arbitrary units are used for the expression of results. In this review I will argue against the use of the term quantitative serology for current tests. Because each test and each antibody isotype determination uses its own references, the term semiquantitative better describes these methods. The introduction of really quantitative serology could both benefit from and drive forward systems immunological approach to immunity.

Từ khóa


Tài liệu tham khảo

Arnold KB, Chung AW (2018) Prospects from systems serology research. Immunology 153:279–289. https://doi.org/10.1111/imm.12861

Bauer A, Kuster B (2003) Affinity purification-mass spectrometry. Eur J Biochem 270:570–578. https://doi.org/10.1046/j.1432-1033.2003.03428.x

Bölke E, Matuschek C, Fischer JC (2020) Loss of anti-SARS-CoV-2 antibodies in mild Covid-19. N Engl J Med 383:1694–1695. https://doi.org/10.1056/NEJMc2027051

Bransburg-Zabary S, Kenett DY, Dar G, Madi A, Merbl Y, Quintana FJ, Tauber AI, Cohen IR, Ben-Jacob E (2013) Individual and meta-immune networks. PhysBiol 10:025003. https://doi.org/10.1088/1478-3975/10/2/025003

De Taeye SW, Rispens T, Vidarsson G (2019) The ligands for human igg and their effector functions. Antibodies (Basel). https://doi.org/10.3390/antib8020030

Dekkers G, Treffers L, Plomp R, Bentlage AEH, de Boer M, Koeleman CAM, Lissenberg-Thunnissen SN, Visser R, Brouwer M, Mok JY, Matlung H, van den Berg TK, van Esch WJE, Kuijpers TW, Wouters D, Rispens T, Wuhrer M, Vidarsson G (2017) Decoding the human immunoglobulin G-glycan repertoire reveals a spectrum of Fc-receptor- and complement-mediated-effector activities. Front Immunol 8:877. https://doi.org/10.3389/fimmu.2017.00877

Dillner J (2005) Toward “serolomics”: papillomavirus serology is taking a technologic lead in high-throughput multiplexed antibody analysis. ClinChem 51:1768–1769. https://doi.org/10.1373/clinchem.2005.055483

Erdei A, Füst G, Gergely J (1991) The role of C3 in the immune response. Immunol Today 12:332–337. https://doi.org/10.1016/0167-5699(91)90011-H

Erdei A, Prechl J, Isaák A, Molnár E (2003) Regulation of B-cell activation by complement receptors CD21 and CD35. Curr Pharm Des 9:1849–1860

Erdei A, Isaák A, Török K, Sándor N, Kremlitzka M, Prechl J, Bajtay Z (2009) Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. MolImmunol 46:2767–2773. https://doi.org/10.1016/j.molimm.2009.05.181

Erdei A, Sándor N, Mácsik-Valent B, Lukácsi S, Kremlitzka M, Bajtay Z (2016) The versatile functions of complement C3-derived ligands. Immunol Rev 274:127–140. https://doi.org/10.1111/imr.12498

Heidelberger M, Kendall FE (1935) A quantitative theory of the precipitin reaction : iii. the reaction between crystalline egg albumin and its homologous antibody. J Exp Med 62:697–720. https://doi.org/10.1084/jem.62.5.697

Herbáth M, Papp K, Balogh A, Matkó J, Prechl J (2014) Exploiting fluorescence for multiplex immunoassays on protein microarrays. Method ApplFluoresc 2:032001. https://doi.org/10.1088/2050-6120/2/3/032001

Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125C:373–389

Kecse-Nagy C, Szittner Z, Papp K, Hegyi Z, Rovero P, Migliorini P, Lóránd V, Homolya L, Prechl J (2016) Characterization of NF-κB reporter U937 cells and their application for the detection of inflammatory immune-complexes. PLoS ONE 11:e0156328. https://doi.org/10.1371/journal.pone.0156328

Kim D, Park D (2019) Deep sequencing of B cell receptor repertoire. BMB Rep 52:540–547. https://doi.org/10.5483/BMBRep.2019.52.9.192

Ladwig PM, Barnidge DR, Willrich MAV (2017) Mass spectrometry approaches for identification and quantitation of therapeutic monoclonal antibodies in the clinical laboratory. Clin Vaccine Immunol. https://doi.org/10.1128/CVI.00545-16

Landsteiner K, van der Scheer J (1936) On cross reactions of immune sera to azoproteins. J Exp Med 63:325–339. https://doi.org/10.1084/jem.63.3.325

Li X, Gibson AW, Kimberly RP (2014) Human FcR polymorphism and disease. Curr Top MicrobiolImmunol 382:275–302. https://doi.org/10.1007/978-3-319-07911-0_13

Loos C, Lauffenburger DA, Alter G (2020) Dissecting the antibody-OME: past, present, and future. CurrOpinImmunol 65:89–96. https://doi.org/10.1016/j.coi.2020.06.003

Lukácsi S, Nagy-Baló Z, Erdei A, Sándor N, Bajtay Z (2017) The role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in complement-mediated phagocytosis and podosome formation by human phagocytes. ImmunolLett 189:64–72. https://doi.org/10.1016/j.imlet.2017.05.014

Lukácsi S, Mácsik-Valent B, Nagy-Baló Z, Kovács KG, Kliment K, Bajtay Z, Erdei A (2020) Utilization of complement receptors in immune cell-microbe interaction. FEBS Lett 594:2695–2713. https://doi.org/10.1002/1873-3468.13743

Madi A, Kenett DY, Bransburg-Zabary S, Merbl Y, Quintana FJ, Tauber AI, Cohen IR, Ben-Jacob E (2011) Network theory analysis of antibody-antigen reactivity data: the immune trees at birth and adulthood. PLoS ONE 6:e17445. https://doi.org/10.1371/journal.pone.0017445

Manivel V, Bayiroglu F, Siddiqui Z, Salunke DM, Rao KVS (2002) The primary antibody repertoire represents a linked network of degenerate antigen specificities. J Immunol 169:888–897. https://doi.org/10.4049/jimmunol.169.2.888

Mari A, Scala E (2006) Allergome: a unifying platform. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M 29–39; discussion 39.

Miho E, Roškar R, Greiff V, Reddy ST (2019) Large-scale network analysis reveals the sequence space architecture of antibody repertoires. Nat Commun 10:1321. https://doi.org/10.1038/s41467-019-09278-8

Molnár E, Erdei A, Prechl J (2008a) Novel roles for murine complement receptors type 1 and 2 I. regulation of B cell survival and proliferation by CR1/2. ImmunolLett 116:156–162. https://doi.org/10.1016/j.imlet.2007.12.007

Molnár E, Prechl J, Erdei A (2008b) Novel roles for murine complement receptors type 1 and 2 II. expression and function of CR1/2 on murine mesenteric lymph node T cells. ImmunolLett 116:163–167. https://doi.org/10.1016/j.imlet.2007.12.010

Nimmerjahn F, Ravetch JV (2007) Fc-Receptors as Regulators of Immunity. Elsevier, pp 179–204

Papp K, Szekeres Z, Terényi N, Isaák A, Erdei A, Prechl J (2007) On-chip complement activation adds an extra dimension to antigen microarrays. Mol Cell Proteom 6:133–140. https://doi.org/10.1074/mcp.T600036-MCP200

Papp K, Szekeres Z, Erdei A, Prechl J (2008a) Two-dimensional immune profiles improve antigen microarray-based characterization of humoral immunity. Proteomics 8:2840–2848. https://doi.org/10.1002/pmic.200800014

Papp K, Végh P, Miklós K, Németh J, Rásky K, Péterfy F, Erdei A, Prechl J (2008b) Detection of complement activation on antigen microarrays generates functional antibody profiles and helps characterization of disease-associated changes of the antibody repertoire. J Immunol 181:8162–8169. https://doi.org/10.4049/jimmunol.181.11.8162

Papp K, Végh P, Tchorbanov A, Vassilev T, Erdei A, Prechl J (2010) Progression of lupus-like disease drives the appearance of complement-activating IgG antibodies in MRL/lpr mice. Rheumatology (Oxford) 49:2273–2280. https://doi.org/10.1093/rheumatology/keq278

Papp K, Végh P, Hóbor R, Erdei A, Prechl J (2012a) Characterization of factors influencing on-chip complement activation to optimize parallel measurement of antibody and complement proteins on antigen microarrays. J Immunol Methods 375:75–83. https://doi.org/10.1016/j.jim.2011.09.009

Papp K, Végh P, Hóbor R, Szittner Z, Vokó Z, Podani J, Czirják L, Prechl J (2012b) Immune complex signatures of patients with active and inactive SLE revealed by multiplex protein binding analysis on antigen microarrays. PLoS ONE 7:e44824. https://doi.org/10.1371/journal.pone.0044824

Papp K, Holczer E, Kecse-Nagy C, Szittner Z, Lóránd V, Rovero P, Prechl J, Fürjes P (2017) Multiplex determination of antigen specific antibodies with cell binding capability in a self-driven microfluidic system. Sens Actuators B Chem 238:1092–1097. https://doi.org/10.1016/j.snb.2016.07.132

Prechl J (2017) A generalized quantitative antibody homeostasis model: antigen saturation, natural antibodies and a quantitative antibody network. ClinTranslImmunol 6:e131. https://doi.org/10.1038/cti.2016.90

Prechl J (2020) Network organization of antibody interactions in sequence and structure space: the RADARS model. Antibodies (Basel). https://doi.org/10.3390/antib9020013

Prechl J, Papp K, Erdei A (2010) Antigen microarrays: descriptive chemistry or functional immunomics? Trends Immunol 31:133–137. https://doi.org/10.1016/j.it.2010.01.004

Prechl J, Szittner Z, Papp K (2012) Complementing antibody profiles: assessing antibody function on antigen microarrays. ImmunolLett 143:101–105. https://doi.org/10.1016/j.imlet.2012.01.011

Prechl J, Papp K, Hérincs Z, Péterfy H, Lóránd V, Szittner Z, Estonba A, Rovero P, Paolini I, Del Amo J, Uribarri M, Alcaro MC, Ruiz-Larrañaga O, Migliorini P, Czirják L (2016) Serological and genetic evidence for altered complement system functionality in systemic lupus erythematosus: findings of the GAPAID consortium. PLoS ONE 11:e0150685. https://doi.org/10.1371/journal.pone.0150685

Robinson WH (2015) Sequencing the functional antibody repertoire–diagnostic and therapeutic discovery. Nat Rev Rheumatol 11:171–182. https://doi.org/10.1038/nrrheum.2014.220

Sándor M, Füst G, Medgyesi GA, Erdei A, Gergely J (1979) The heterogeneity of Fc receptors on human peripheral mononuclear blood cells. Immunology 38:553–560

Sándor N, Pap D, Prechl J, Erdei A, Bajtay Z (2009) A novel, complement-mediated way to enhance the interplay between macrophages, dendritic cells and T lymphocytes. MolImmunol 47:438–448. https://doi.org/10.1016/j.molimm.2009.08.025

Schuurs AH, van Weemen BK (1980) Enzyme-immunoassay: a powerful analytical tool. J Immunoass 1:229–249. https://doi.org/10.1080/01971528008055786

Szittner Z, Papp K, Sándor N, Bajtay Z, Prechl J (2013) Application of fluorescent monocytes for probing immune complexes on antigen microarrays. PLoS ONE 8:e72401. https://doi.org/10.1371/journal.pone.0072401

Szittner Z, Bentlage AEH, Rovero P, Migliorini P, Lóránd V, Prechl J, Vidarsson G (2016) Label-free detection of immune complexes with myeloid cells. ClinExpImmunol 185:72–80. https://doi.org/10.1111/cei.12788

Van Weemen BK, Schuurs AHWM (1971) Immunoassay using antigen-enzyme conjugates. FEBS Lett 15:232–236. https://doi.org/10.1016/0014-5793(71)80319-8

Verbeek JS, Hazenbos WL, Capel PJ, van de Winkel JG (1997) The role of FcR in immunity: lessons from gene targeting in mice. Res Immunol 148:466–474. https://doi.org/10.1016/s0923-2494(97)82673-9

Vidarsson G, Dekkers G, Rispens T (2014) IgG subclasses and allotypes: from structure to effector functions. Front Immunol 5:520. https://doi.org/10.3389/fimmu.2014.00520

Vita R, Mahajan S, Overton JA, Dhanda SK, Martini S, Cantrell JR, Wheeler DK, Sette A, Peters B (2019) The immune epitope database (IEDB): 2018 update. Nucleic Acids Res 47:D339–D343. https://doi.org/10.1093/nar/gky1006

Wang Z, Liu X, Muther J, James JA, Smith K, Wu S (2019) Top-down mass spectrometry analysis of human serum autoantibody antigen-binding fragments. Sci Rep 9:2345. https://doi.org/10.1038/s41598-018-38380-y