Latex Agglutination Enables Functional Assessment of Immune Activity and Differentiation of Therapy-Induced Humoral Responses
https://doi.org/10.20340/vmi-rvz.2025.5.CLIN.1
Abstract
Systemic activation of the humoral immune system occurs in malignancies, autoimmune diseases, infections, and pregnancy, yet its quantitative assessment with simple laboratory tools remains challenging. We developed a rapid, low-cost latex agglutination test (LAT) as an antigen-agnostic sensor of systemic humoral activation. The assay measures visual agglutination of uncoated 2-μm latex microspheres by serum antibodies and reports a semi-quantitative titer (highest dilution with visible agglutination). Sera from cancer patients, pregnant women, and healthy volunteers were tested. Uncoated beads revealed increased systemic activity in select groups: in breast cancer (n=11), 73% maintained low titers (≤1:8) while 27% showed therapy-associated rises up to 1:64; HER2-positive cases exhibited transient or sustained elevations during targeted therapy, and CDK4/6 plus endocrine therapy showed delayed increases. Pregnant women displayed high titers (1:32–1:64), and healthy volunteers were negative. These data indicate that LAT captures systemic activation and can distinguish therapy-associated increases, supporting its use as a universal serological marker that complements antigen-specific assays in clinical and research settings.
Keywords
About the Authors
E. ShaninБолгария
Elena Shanin, PhD (Dr. rer. nat. in Biochemistry), Co-founder and CEO, 74, Zhechka Karamfilova St., Burgas;
Rector, 1, Prof. Yakimov Blvd., Burgas
F. Broecker
Болгария
Felix Broecker, PhD (Dr. rer. nat. in Biochemistry), MBA, Co-founder and CTO,
74, Zhechka Karamfilova St., Burgas
M. V. Sizova
Россия
Mariya V. Sizova, Project Manager in Analytical Research and Development Laboratory,
227, Chapaevskaya St., Samara, 443001
N. A. Gorburnov
Россия
Nikolay A. Gorbunov, Assistant at the Department of Morphology and Pathology, Head of the Laboratory for Development and Analytical Research,
227, Chapaevskaya St., Samara, 443001
A. A. Supil'nikov
Россия
Aleksey A. Supilnikov, Cand. Sci. (Med.), Associate Professor, First Vicerector for Scientific Activity,
227, Chapaevskaya St., Samara, 443001
A. N. Lysova
Россия
Anna N. Lysova, Cand. Sci. (Med.), Associate Professor, Vice-Rector for International Cooperation and Education,
227, Chapaevskaya St., Samara, 443001
N. A. Lysov
Россия
Nikolay A. Lysov, Dr. Sci. (Med.), Honorary Worker of Higher Professional Education of the Russian Federation, Professor of the Department of Surgical Diseases,
1, Prof. Yakimov Blvd., Burgas;
227, Chapaevskaya St., Samara, 443001
References
1. SINGER JM, PLOTZ CM. The latex fixation test for rheumatoid arthritis using patients' own gamma globulin. Arthritis Rheum. 1958;1(2):142- 146. https://doi.org/10.1002/art.1780010206
2. SINGER JM. The latex fixation test in rheumatic diseases: a review. Am J Med. 1961;31:766-779. https://doi.org/10.1016/0002- 9343(61)90161-9
3. Smith LP, Hunter KW Jr, Hemming VG, Fischer GW. Improved detection of bacterial antigens by latex agglutination after rapid extraction from body fluids. J Clin Microbiol. 1984;20(5):981-984. https://doi.org/10.1128/jcm.20.5.981-984.1984
4. Thorns CJ, McLaren IM, Sojka MG. The use of latex particle agglutination to specifically detect Salmonella enteritidis. Int J Food Microbiol. 1994;21(1-2):47-53. https://doi.org/10.1016/0168-1605(94)90199-6
5. Bernard AM, Foidart JM, Mahieu P, Viau C, Lauwerys RR. Detection of anti-laminin antibodies in sera by latex agglutination. Clin Chem. 1986;32(8):1468-1472.
6. Hevey MA, George IA, Rauseo AM, Larson L, Powderly W, Spec A. Performance of the Lateral Flow Assay and the Latex Agglutination Serum Cryptococcal Antigen Test in Cryptococcal Disease in Patients with and without HIV. J Clin Microbiol. 2020;58(11):e01563-20. Published 2020 Oct 21. https://doi.org/10.1128/JCM.01563-20
7. Madrid FF, Maroun MC, Olivero OA, et al. Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis. BMC Cancer. 2015;15:407. Published 2015 May 15. https://doi.org/10.1186/s12885-015-1385-8
8. Anderson KS, LaBaer J. The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res. 2005;4(4):1123-1133. https://doi.org/10.1021/pr0500814
9. Montero-Calle A, Garranzo-Asensio M, Moreno-Casbas MT, Campuzano S, Barderas R. Autoantibodies in cancer: a systematic review of their clinical role in the most prevalent cancers. Front Immunol. 2024;15:1455602. Published 2024 Aug 21. https://doi.org/10.3389/fimmu.2024.1455602
10. Chapman CJ, Murray A, McElveen JE, et al. Autoantibodies in lung cancer: possibilities for early detection and subsequent cure. Thorax. 2008;63(3):228-233. https://doi.org/10.1136/thx.2007.083592
11. Tan EM, Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966;96(3):464-471.
12. Williams KC, Gault A, Anderson AE, et al. Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations. Front Immunol. 2023;14:1122430. Published 2023 Jan 26. https://doi.org/10.3389/fimmu.2023.1122430
13. Choi J, Lee SY. Clinical Characteristics and Treatment of Immune-Related Adverse Events of Immune Checkpoint Inhibitors. Immune Netw. 2020;20(1):e9. Published 2020 Feb 17. https://doi.org/10.4110/in.2020.20.e9
14. Hudis CA. Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39-51. https://doi.org/10.1056/NEJMra043186
15. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109- 119. https://doi.org/10.1056/NEJMoa1113216
16. Min HK, Kim IH, Kim JY, et al. Trastuzumab-associated autoimmune thyroid disease in a patient with metastatic breast cancer. Korean J Intern Med. 2016;31(3):608-611. https://doi.org/10.3904/kjim.2014.031
17. Sánchez-Bayona R, Garcia Del Barrio MA, Alegre E, Fernandez-Hidalgo OA, Eslava MS. Trastuzumab and thyroid dysfunction: An association to be aware of. J Cancer Res Ther. 2022;18(4):1183-1185. https://doi.org/10.4103/jcrt.JCRT_66_19
18. Deng J, Wang ES, Jenkins RW, et al. CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov. 2018;8(2):216-233. https://doi.org/10.1158/2159-8290.CD-17-0915
19. Goel S, DeCristo MJ, McAllister SS, Zhao JJ. CDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest. Trends Cell Biol. 2018;28(11):911-925. https://doi.org/10.1016/j.tcb.2018.07.002
20. Liu Y, Deng Y, Yang C, Naranmandura H. Double-Faced Immunological Effects of CDK4/6 Inhibitors on Cancer Treatment: Challenges and Perspectives. Bioengineering (Basel). 2024;11(11):1084. Published 2024 Oct 29. https://doi.org/10.3390/bioengineering11111084
21. Shams'ili S, Grefkens J, de Leeuw B, et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain. 2003;126(Pt 6):1409-1418. https://doi.org/10.1093/brain/awg133
22. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. https://doi.org/10.1089/thy.2011.0087
23. Yang S, Huang Z, Zhang Y, et al. Association of Maternal Thyroglobulin Antibody with Preterm Birth in Euthyroid Women. J Clin Endocrinol Metab. Published online February 25, 2025. https://doi.org/10.1210/clinem/dgaf118
24. Murvai VR, Galiș R, Panaitescu A, et al. Antiphospholipid syndrome in pregnancy: a comprehensive literature review. BMC Pregnancy Childbirth. 2025;25(1):337. Published 2025 Mar 24. https://doi.org/10.1186/s12884-025-07471-w
25. Gerede A, Oikonomou E, Stavros S, et al. Systemic Lupus Erythematosus in Pregnancy. Med Sci (Basel). 2025;13(3):174. Published 2025 Sep 4. https://doi.org/10.3390/medsci13030174
26. Heydari K, Rahnavard M, Ghahramani S, et al. Global prevalence and incidence of inflammatory bowel disease: a systematic review and meta-analysis of population-based studies. Gastroenterol Hepatol Bed Bench. 2025;18(2):132-146. https://doi.org/10.22037/ghfbb.v18i2.3105
27. Fu L, Ge M, Zhu F, et al. Rheumatoid arthritis continues to increase in low-middle SDI and low SDI quintiles based on GBD 1990-2021. BMC Rheumatol. 2025;9(1):114. Published 2025 Oct 3. https://doi.org/10.1186/s41927-025-00570-3
28. Olsen NJ, Choi MY, Fritzler MJ. Emerging technologies in autoantibody testing for rheumatic diseases. Arthritis Res Ther. 2017;19(1):172. Published 2017 Jul 24. https://doi.org/10.1186/s13075-017-1380-3
29. Cinquanta L, Fontana DE, Bizzaro N. Chemiluminescent immunoassay technology: what does it change in autoantibody detection?. Auto Immun Highlights. 2017;8(1):9. https://doi.org/10.1007/s13317-017-0097-2
30. Chan EK, Damoiseaux J, Carballo OG, et al. Report of the First International Consensus on Standardized Nomenclature of Antinuclear Antibody HEp-2 Cell Patterns 2014-2015. Front Immunol. 2015;6:412. Published 2015 Aug 20. https://doi.org/10.3389/fimmu.2015.00412
31. Satoh M, Tanaka S, Chan EK. The uses and misuses of multiplex autoantibody assays in systemic autoimmune rheumatic diseases. Front Immunol. 2015;6:181. Published 2015 Apr 21. https://doi.org/10.3389/fimmu.2015.00181
32. Norde W. Adsorption of proteins from solution at the solid-liquid interface. Adv Colloid Interface Sci. 1986;25(4):267-340. https://doi.org/10.1016/0001-8686(86)80012-4
33. Hasani S, Derakhshani A, Hasani B, Navaei T. Protein adsorption on polymeric surfaces. In: Handbook of Polymers in Medicine. Woodhead Publishing; 2023:57-85. https://doi.org/10.1016/B978-0-12-823797-7.00003-4
34. Koussiouris J, Chandran V. Autoantibodies in Psoriatic Disease. J Appl Lab Med. 2022;7(1):281-293. https://doi.org/10.1093/jalm/jfab120
35. Ten Bergen LL, Petrovic A, Aarebrot AK, Appel S. Current knowledge on autoantigens and autoantibodies in psoriasis. Scand J Immunol. 2020;92(4):e12945. https://doi.org/10.1111/sji.12945
36. Holmes J, Fairclough LC, Todd I. Atopic dermatitis and autoimmunity: the occurrence of autoantibodies and their association with disease severity. Arch Dermatol Res. 2019;311(3):141-162. https://doi.org/10.1007/s00403-019-01890-4
37. Hudis CA. Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39-51. https://doi.org/10.1056/NEJMra043186
38. Galluzzi L, Buqué A, Kepp O, Zitvogel L, Kroemer G. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97-111. https://doi.org/10.1038/nri.2016.107
39. Stanton SE, Adams S, Disis ML. Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. JAMA Oncol. 2016;2(10):1354-1360. https://doi.org/10.1001/jamaoncol.2016.1061
40. Piccinni MP, Lombardelli L, Logiodice F, Kullolli O, Parronchi P, Romagnani S. How pregnancy can affect autoimmune diseases progression? Clin Mol Allergy. 2016;14:11. Published 2016 Sep 15. https://doi.org/10.1186/s12948-016-0048-x
41. Caretto A, Pedone E, Laurenzi A, et al. Type 1 diabetes diagnosed during pregnancy-an unusual but important challenge: a case series and review of literature. Front Med (Lausanne). 2025;12:1656833. Published 2025 Sep 12. https://doi.org/10.3389/fmed.2025.1656833
42. Balucan FS, Morshed SA, Davies TF. Thyroid autoantibodies in pregnancy: their role, regulation and clinical relevance. J Thyroid Res. 2013;2013:182472. https://doi.org/10.1155/2013/182472
43. Gummadi A, Rawat A. Autoantibodies in Pregnancy. In: Sharma S, ed. Women’s Health in Autoimmune Diseases. Springer; 2020:45-55. https://doi.org/10.1007/978-981-15-0114-2_4
44. Murvai VR, Galiș R, Panaitescu A, et al. Antiphospholipid syndrome in pregnancy: a comprehensive literature review. BMC Pregnancy Childbirth. 2025;25(1):337. Published 2025 Mar 24. https://doi.org/10.1186/s12884-025-07471-w
45. Inagaki Y, Takeshima K, Nishi M, et al. The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study. Endocr J. 2020;67(8):859-868. https://doi.org/10.1507/endocrj.EJ19-0604
46. Giannakaki AG, Giannakaki MN, Bothou A, et al. Current Approaches to the Management of Rheumatic Diseases in Pregnancy: Risk Stratification, Therapeutic Advances, and Maternal-Fetal Outcomes. J Pers Med. 2025;15(9):406. Published 2025 Sep 1. https://doi.org/10.3390/jpm15090406
47. Xiang J, Bao R, Zhang J, Cai Z. Association between antivimentin/cardiolipin antibodies and pregnancy loss in pregnant women with at least one spontaneous miscarriage. BMC Immunol. 2025;26(1):56. Published 2025 Jul 29. https://doi.org/10.1186/s12865-025-00737-0
48. Werner LL, Turnwald GH, Willard MD. Immunologic and Plasma Protein Disorders. Small Animal Clinical Diagnosis by Laboratory Methods. 2004;290-305. https://doi.org/10.1016/B0-72-168903-5/50017-3
Review
For citations:
Shanin E., Broecker F., Sizova M.V., Gorburnov N.A., Supil'nikov A.A., Lysova A.N., Lysov N.A. Latex Agglutination Enables Functional Assessment of Immune Activity and Differentiation of Therapy-Induced Humoral Responses. Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH). 2025;15(5):14-28. (In Russ.) https://doi.org/10.20340/vmi-rvz.2025.5.CLIN.1
JATS XML


















