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Advancing Autoantibody Detection: A Journey from Conventional to State-of-the-Art Methods
Vol. 32 No. 2 (2024), Review articles
Vol. 32 No. 2 (2024)

Advancing Autoantibody Detection: A Journey from Conventional to State-of-the-Art Methods

Review articles
https://doi.org/10.35465/32.2.2024.pp21-33
Published December 22, 2024
Y. Acosta-Ampudia
D. Monsalve
Carolina Ramirez-Santana
Center for Autoimmune Diseases Research (CREA), School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia
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Keywords

Autoimmune diseases, autoantibodies, antigen arrays, immunoassay

How to Cite

Acosta-Ampudia, Y., Monsalve, D., & Ramirez-Santana, C. (2024). Advancing Autoantibody Detection: A Journey from Conventional to State-of-the-Art Methods. Rheumatology (Bulgaria), 32(2), 21-33. https://doi.org/10.35465/32.2.2024.pp21-33
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Abstract

Autoimmune diseases are a diverse group of disorders characterized by immune disturbances that cause aberrant B cell and T cell reactivity to normal constituents of the host1. Autoantibodies are commonly found in individuals with autoimmune diseases. A large number of autoantibodies are directed against intracellular or extracellular targets such as nucleic acids, structural proteins, enzymes, RNA binding proteins, receptors, cytokines, among others2. The detection of these autoantibodies is key to the diagnosis and classification of patients with autoimmune diseases. In addition, some studies have shown that autoantibodies can appear years before the onset of an autoimmune disease; therefore, the detection of these antibodies would serve as early predictors of risk and would also help to choose a possible therapeutic intervention to prevent or delay the disease progression3. Several methods, such as enzyme-linked immunosorbent assay (ELISA), immunofluorescence, fixed tissue or cell-based assays, are commonly used for the detection of autoantibodies. Although these technologies are limited in sensitivity, specificity, and sample throughput, therefore, new experimental techniques are continuously developed to discover novel autoantigens involved in autoimmune diseases4. There are several limitations in the detection of autoantibodies, such as sensitivity and specificity, temporal variability in autoantibody levels, technical limitations, subjective interpretation, and lack of standards and quality controls in the tests. Autoantibody tests are only a diagnostic tool and must be used in combination with clinical evaluation for an accurate diagnosis. In this chapter, we will describe the technologies used in the detection of classic and new autoantibodies, exploring the assessment of clinical relevance, accuracy, validation, and possible regulatory requirements as an approved diagnostic test that could be promoted in routine clinical practice.

https://doi.org/10.35465/32.2.2024.pp21-33
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References

  1. Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278(4):369-395. doi:10.1111/joim.12395
  2. Burbelo PD, Iadarola MJ, Keller JM, Warner BM. Autoantibodies Targeting Intracellular and Extracellular Proteins in Autoimmunity. Front Immunol. 2021;12:548469. doi:10.3389/fimmu.2021.548469
  3. Burbelo PD, O’Hanlon TP. New autoantibody detection technologies yield novel insights into autoimmune disease. Curr Opin Rheumatol. 2014;26(6):717-723. doi:10.1097/BOR.0000000000000107
  4. Carlton LH, McGregor R, Moreland NJ. Human antibody profiling technologies for autoimmune disease. Immunol Res. Published online January 2023:1-12. doi:10.1007/s12026-023-09362-8
  5. Xiao ZX, Miller JS, Zheng SG. An updated advance of autoantibodies in autoimmune diseases. Autoimmun Rev. 2021;20(2):102743. doi:10.1016/j.autrev.2020.102743
  6. Milo R, Kahana E. Multiple sclerosis: geoepidemiology, genetics and the environment. Autoimmun Rev. 2010;9(5):A387-94. doi:10.1016/j.autrev.2009.11.010
  7. Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1316-1322. doi:10.1136/annrheumdis-2013-204627
  8. Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. Published online May 2023:1-16. doi:10.1038/s41581-023-00720-1
  9. Yu X, Wax J, Riemekasten G, Petersen F. Functional autoantibodies: Definition, mechanisms, origin and contributions to autoimmune and non-autoimmune disorders. Autoimmun Rev. Published online 2023:103386. doi:https://doi.org/10.1016/j.autrev.2023.103386
  10. Pacheco Y, Monsalve DM, Acosta-Ampudia Y, Rojas C, Anaya JM, Ramírez-Santana C. Antinuclear autoantibodies: discordance among four different assays. Ann Rheum Dis. 2020;79(1):e6. doi:10.1136/annrheumdis-2018-214693
  11. Tozzoli R, Antico A, Porcelli B, Bassetti D. Automation in indirect immunofluorescence testing: a new step in the evolution of the autoimmunology laboratory. Auto- Immun highlights. 2012;3(2):59-65. doi:10.1007/s13317-012-0035-2
  12. Chan EKL, Damoiseaux J, de Melo Cruvinel W, et al. Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015. Lupus. 2016;25(8):797-804. doi:10.1177/0961203316640920
  13. Irure-Ventura J, López-Hoyos M. The Past, Present, and Future in Antinuclear Antibodies (ANA). Diagnostics (Basel, Switzerland). 2022;12(3). doi:10.3390/diagnostics12030647
  14. Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151-1159. doi:10.1136/annrheumdis-2018-214819
  15. Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res. 2014;2014:315179. doi:10.1155/2014/315179
  16. Mahler M, Ngo JT, Schulte-Pelkum J, Luettich T, Fritzler MJ. Limited reliability of the indirect immunofluorescence technique for the detection of anti-Rib-P antibodies. Arthritis Res Ther. 2008;10(6):R131. doi:10.1186/ar2548
  17. Keech CL, McCluskey J, Gordon TP. Transfection and overexpression of the human 60-kDa Ro/SS-A autoantigen in HEp-2 cells. Clin Immunol Immunopathol. 1994;73(1):146-151. doi:10.1006/clin.1994.1181
  18. Malyavantham K, Suresh L. Analysis of DFS70 pattern and impact on ANA screening using a novel HEp-2 ELITE/DFS70 knockout substrate. Auto- Immun highlights. 2017;8(1):3. doi:10.1007/s13317-017-0091-8
  19. Bertin D, Jourde-Chiche N, Bongrand P, Bardin N. Original approach for automated quantification of antinuclear autoantibodies by indirect immunofluorescence. Clin Dev Immunol. 2013;2013:182172. doi:10.1155/2013/182172
  20. Roggenbuck D, Hiemann R, Schierack P, Reinhold D, Conrad K. Digital immunofluorescence enables automated detection of antinuclear antibody endpoint titers avoiding serial dilution. Clin Chem Lab Med. 2014;52(2):e9-11. doi:10.1515/cclm-2013-0543
  21. Fenger M, Wiik A, Høier-Madsen M, et al. Detection of antinuclear antibodies by solid-phase immunoassays and immunofluorescence analysis. Clin Chem. 2004;50(11):2141-2147. doi:10.1373/clinchem.2004.038422
  22. Copple SS, Sawitzke AD, Wilson AM, Tebo AE, Hill HR. Enzyme-linked immunosorbent assay screening then indirect immunofluorescence confirmation of antinuclear antibodies: a statistical analysis. Am J Clin Pathol. 2011;135(5):678-684. doi:10.1309/AJCP6R8EELGODAYW
  23. Deutschmann C, Roggenbuck D, Schierack P, Rödiger S. Autoantibody testing by enzyme-linked immunosorbent assay-a case in which the solid phase decides on success and failure. Heliyon. 2020;6(1):e03270. doi:10.1016/j.heliyon.2020.e03270
  24. Lee SA, Kahng J, Kim Y, et al. Comparative study of immunofluorescent antinuclear antibody test and line immunoassay detecting 15 specific autoantibodies in patients with systemic rheumatic disease. J Clin Lab Anal. 2012;26(4):307-314. doi:10.1002/jcla.21522
  25. To F, Ventín-Rodríguez C, Elkhalifa S, Lilleker JB, Chinoy H. Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results. BMC Rheumatol. 2020;4:28. doi:10.1186/s41927-020-00132-9
  26. Mahler M, Bentow C, Serra J, Fritzler MJ. Detection of autoantibodies using chemiluminescence technologies. Immunopharmacol Immunotoxicol. 2016;38(1):14-20. doi:10.3109/08923973.2015.1077461
  27. Ghillani P, Rouquette AM, Desgruelles C, et al. Evaluation of the LIAISON ANA screen assay for antinuclear antibody testing in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:407-413. doi:10.1196/annals.1398.046
  28. Mahler M, Gascon C, Patel S, et al. Rpp25 is a major target of autoantibodies to the Th/To complex as measured by a novel chemiluminescent assay. Arthritis Res Ther. 2013;15(2):R50. doi:10.1186/ar4210
  29. Musset L, Miyara M, Benveniste O, et al. Analysis of autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase using different technologies. J Immunol Res. 2014;2014:405956. doi:10.1155/2014/405956
  30. Damoiseaux J, van Beers J. Autoantibodies to dsDNA in the diagnosis, classification and follow-up of patients with systemic lupus erythematosus. J Transl Autoimmun. 2023;6:100191. doi:10.1016/j.jtauto.2023.100191
  31. Rönnelid J, Turesson C, Kastbom A. Autoantibodies in Rheumatoid Arthritis - Laboratory and Clinical Perspectives. Front Immunol. 2021;12:685312. doi:10.3389/fimmu.2021.685312
  32. Cinquanta L, Fontana DE, Bizzaro N. Chemiluminescent immunoassay technology: what does it change in autoantibody detection? Auto- Immun highlights. 2017;8(1):9. doi:10.1007/s13317-017-0097-2
  33. Ricken G, Schwaiger C, De Simoni D, et al. Detection Methods for Autoantibodies in Suspected Autoimmune Encephalitis. Front Neurol. 2018;9:841. doi:10.3389/fneur.2018.00841
  34. Gao F, Zhang Y, Lv J, et al. How to improve the sensitivity and specificity of cell-based assays in detecting autoantibodies in neuroimmune diseases. Ann Transl Med. 2023;11(7):281. doi:10.21037/atm-21-3072
  35. Rodriguez Cruz PM, Huda S, López-Ruiz P, Vincent A. Use of cell-based assays in myasthenia gravis and other antibody-mediated diseases. Exp Neurol. 2015;270:66-71. doi:https://doi.org/10.1016/j.expneurol.2015.01.011
  36. Molina RD, Conzatti LP, da Silva APB, et al. Detection of autoantibodies in central nervous system inflammatory disorders: Clinical application of cell-based assays. Mult Scler Relat Disord. 2020;38:101858. doi:10.1016/j.msard.2019.101858
  37. Liu E, Eisenbarth GS. Accepting clocks that tell time poorly: fluid-phase versus standard ELISA autoantibody assays. Clin Immunol. 2007;125(2):120-126. doi:10.1016/j.clim.2007.08.005
  38. Bingley PJ, Bonifacio E, Williams AJ, Genovese S, Bottazzo GF, Gale EA. Prediction of IDDM in the general population: strategies based on combinations of autoantibody markers. Diabetes. 1997;46(11):1701-1710. doi:10.2337/diab.46.11.1701
  39. Valdez SN, Iacono RF, Villalba A, Cardoso Landaburu A, Ermácora MR, Poskus E. A radioligand-binding assay for detecting antibodies specific for proinsulin and insulin using 35S-proinsulin. J Immunol Methods. 2003;279(1):173-181. doi:https://doi.org/10.1016/S0022-1759(03)00197-2
  40. Wenzlau JM, Liu Y, Yu L, et al. A common nonsynonymous single nucleotide polymorphism in the SLC30A8 gene determines ZnT8 autoantibody specificity in type 1 diabetes. Diabetes. 2008;57(10):2693-2697. doi:10.2337/db08-0522
  41. Shum AK, Alimohammadi M, Tan CL, et al. BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease. Sci Transl Med. 2013;5(206):206ra139. doi:10.1126/scitranslmed.3006998
  42. Burbelo PD, Lebovitz EE, Notkins AL. Luciferase immunoprecipitation systems for measuring antibodies in autoimmune and infectious diseases. Transl Res. 2015;165(2):325-335. doi:10.1016/j.trsl.2014.08.006
  43. Yamakawa M, Mukaino A, Kimura A, et al. Antibodies to the α3 subunit of the ganglionic-type nicotinic acetylcholine receptors in patients with autoimmune encephalitis. J Neuroimmunol. 2020;349:577399. doi:10.1016/j.jneuroim.2020.577399
  44. Hoang TTT, Ichinose K, Morimoto S, Furukawa K, Le LHT, Kawakami A. Measurement of anti-suprabasin antibodies, multiple cytokines and chemokines as potential predictive biomarkers for neuropsychiatric systemic lupus erythematosus. Clin Immunol. 2022;237:108980. doi:10.1016/j.clim.2022.108980
  45. Mukaino A, Nakane S, Higuchi O, et al. Insights from the ganglionic acetylcholine receptor autoantibodies in patients with Sjögren’s syndrome. Mod Rheumatol. 2016;26(5):708-715. doi:10.3109/14397595.2016.1147404
  46. Maeda Y, Nakane S, Higuchi O, et al. Ganglionic acetylcholine receptor autoantibodies in patients with autoimmune diseases including primary biliary cirrhosis. Mod Rheumatol. 2017;27(4):664-668. doi:10.1080/14397595.2016.1226469
  47. Burbelo PD, Gordon SM, Waldman M, et al. Autoantibodies are present before the clinical diagnosis of systemic sclerosis. PLoS One. 2019;14(3):e0214202. doi:10.1371/journal.pone.0214202
  48. Ling Y, Jiang P, Li N, Yan Q, Wang X. A luciferase immunoprecipitation assay for the detection of proinsulin/insulin autoantibodies. Clin Biochem. 2018;54:51-55. doi:https://doi.org/10.1016/j.clinbiochem.2018.02.011
  49. Burbelo PD, Browne SK, Sampaio EP, et al. Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood. 2010;116(23):4848-4858. doi:10.1182/blood-2010-05-286161
  50. Haab BB, Dunham MJ, Brown PO. Protein microarrays for highly parallel detection and quantitation of specific proteins and antibodies in complex solutions. Genome Biol. 2001;2(2):RESEARCH0004. doi:10.1186/gb-2001-2-2-research0004
  51. Ayoglu B, Häggmark A, Neiman M, et al. Systematic antibody and antigen-based proteomic profiling with microarrays. Expert Rev Mol Diagn. 2011;11(2):219-234. doi:10.1586/erm.10.110
  52. Ayoglu B, Häggmark A, Khademi M, et al. Autoantibody Profiling in Multiple Sclerosis Using Arrays of Human Protein Fragments*. Mol Cell Proteomics. 2013;12(9):2657-2672. doi:https://doi.org/10.1074/mcp.M112.026757
  53. Zhu H, Luo H, Yan M, Zuo X, Li QZ. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus. Genomics Proteomics Bioinformatics. 2015;13(4):210-218. doi:https://doi.org/10.1016/j.gpb.2015.09.001
  54. Sokolove J, Lindstrom TM, Robinson WH. Development and deployment of antigen arrays for investigation of B-cell fine specificity in autoimmune disease. Front Biosci (Elite Ed). 2012;4(1):320-330. doi:10.2741/379
  55. Petersson L, Dexlin-Mellby L, Bengtsson AA, Sturfelt G, Borrebaeck CAK, Wingren C. Multiplexing of miniaturized planar antibody arrays for serum protein profiling--a biomarker discovery in SLE nephritis. Lab Chip. 2014;14(11):1931-1942. doi:10.1039/c3lc51420j
  56. Ayoglu B, Schwenk JM, Nilsson P. Antigen arrays for profiling autoantibody repertoires. Bioanalysis. 2016;8(10):1105-1126. doi:10.4155/bio.16.31
  57. Fulton RJ, McDade RL, Smith PL, Kienker LJ, Kettman Jr. JR. Advanced multiplexed analysis with the FlowMetrixTM system. Clin Chem. 1997;43(9):1749-1756. doi:10.1093/clinchem/43.9.1749
  58. Budde P, Zucht HD, Vordenbäumen S, et al. Multiparametric detection of autoantibodies in systemic lupus erythematosus. Lupus. 2016;25(8):812-822. doi:10.1177/0961203316641770
  59. Price J V, Haddon DJ, Kemmer D, et al. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus. J Clin Invest. 2013;123(12):5135-5145. doi:10.1172/JCI70231
  60. Olsen NJ, Choi MY, Fritzler MJ. Emerging technologies in autoantibody testing for rheumatic diseases. Arthritis Res Ther. 2017;19(1):172. doi:10.1186/s13075-017-1380-3
  61. Albon S, Bunn C, Swana G, Karim Y. Performance of a multiplex assay compared to enzyme and precipitation methods for anti-ENA testing in systemic lupus and systemic sclerosis. J Immunol Methods. 2011;365(1-2):126-131. doi:10.1016/j.jim.2010.12.010
  62. Kaul R, Johnson K, Scholz H, Marr G. Performance of the BioPlex 2200 Autoimmune Vasculitis kit. Autoimmun Rev. 2009;8(3):224-227. doi:10.1016/j.autrev.2008.07.033
  63. Sowa M, Großmann K, Scholz J, et al. The CytoBead assay – a novel approach of multiparametric autoantibody analysis in the diagnostics of systemic autoimmune diseases. 2015;38(s1). doi:doi:10.1515/labmed-2015-0036
  64. Sowa M, Grossmann K, Knütter I, et al. Simultaneous automated screening and confirmatory testing for vasculitis-specific ANCA. PLoS One. 2014;9(9):e107743. doi:10.1371/journal.pone.0107743
  65. Abdukhakimova D, Dossybayeva K, Grechka A, et al. Reliability of the Multiplex CytoBead CeliAK Immunoassay to Assess Anti-tTG IgA for Celiac Disease Screening. Front Med. 2021;8:731067. doi:10.3389/fmed.2021.731067
  66. Wang EY, Dai Y, Rosen CE, et al. High-throughput identification of autoantibodies that target the human exoproteome. Cell Reports Methods. 2022;2(2):100172. doi:https://doi.org/10.1016/j.crmeth.2022.100172
  67. Chan EKL, Fritzler MJ, Wiik A, et al. AutoAbSC.Org -- Autoantibody Standardization Committee in 2006. Autoimmun Rev. 2007;6(8):577-580. doi:10.1016/j.autrev.2007.05.001
  68. James K, Carpenter AB, Cook L, Marchand R, Nakamura RM. Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists. Clin Diagn Lab Immunol. 2000;7(3):436-443. doi:10.1128/CDLI.7.3.436-443.2000
  69. Chin A, Choi MY, Fritzler MJ. Gaps and Trends in Autoantibody Testing. J Appl Lab Med. 2022;7(1):362-366. doi:10.1093/jalm/jfab153

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