Exposure to airborne nickel and phenol and features of the immune response mediated by E and G immunoglobulins

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N.V. Zaitseva, О.V. Dolgikh, D.G. Dianova


Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, 82 Monastyrskaya Str., Perm, 614045, Russian Federation


Ambient air pollution with potentially allergenic technogenic haptens facilitates occurrence of atopic reactions and creates favorable conditions for future development of allergic pathologies in exposed population.

The aim of this study was to estimate formation of an IgE-mediated and IgG-mediated specific immune response to low-molecular chemical compounds introduced into the body by inhalation (nickel and phenol used as examples).

The test groups were made of children (n = 99) and adults (n = 57) who lived under exposure to airborne nickel and phenol in levels not exceeding maximum permissible ones (up to 0.7 MPL). The reference groups included children (n = 95) and adults (n = 53) who lived on a conventionally clean territory.

In the test groups, average daily exposure doses of airborne nickel and phenol varied between 0.7•10-6 and 9.3•10-6 mg/(kg•day) for children and between 3.5•10-6 and 5.0•10-5 mg/(kg•day) for adults (the doses were created by emissions from a non-ferrous metallurgy plant); this was 1.5–3.0 times higher than the same indicators in the reference groups. Levels of IgG specific to nickel were more than two times higher in the exposed groups; the exposed children had elevated levels of IgG specific to phenol in their blood, practically three times higher than in the reference group (р < 0.05). By using logistic regression models, we established a significant probabilistic cause-effect relation between elevated nickel levels in children’s blood and elevated levels of IgE-specific to nickel (R2 = 0.87; F = 468.58; р < 0.05). The assessment of the odds ratio made it possible to verify the relationship between nickel levels in blood and the increase in the level of IgE specific to nickel in children (OR = 8.96; 95% CI = 2.00–40.15) and in adults from the test group (OR = 3.12; 95 % CI = 1.10–9.40).

The study results indicate that exposure to low levels of airborne nickel and phenol induces hypersensitivity to technogenic haptens in the exposed children and adults. Its distinctive features are an IgE-mediated reaction to nickel and IgG-mediated reaction to phenol. Hyperproduction of immunoglobulin E specific to nickel as well as IgG-antibodies specific to phenol in the exposed children and adults reflects levels of exposure to airborne nickel and phenol and is a peculiarity of a hyperactive immune response developing in the analyzed children on the test territory.

nickel, phenol, airborne exposure, specific IgG, specific IgE, reagins, sensitivity to haptens, atopic reaction
Zaitseva N.V., Dolgikh О.V., Dianova D.G. Exposure to airborne nickel and phenol and features of the immune response mediated by E and G immunoglobulins. Health Risk Analysis, 2023, no. 2, pp. 160–167. DOI: 10.21668/health.risk/2023.2.16.eng
  1. Štefanac T., Grgas D., Dragičević T.L. Xenobiotics-division and methods of detection: A Review. J. Xenobiot, 2021, vol. 11, no. 4, pp. 130–141. DOI: 10.3390/jox11040009
  2. Oršolić N. Allergic inflammation: Effect of propolis and its flavonoids. Molecules, 2022, vol. 27, no. 19, pp. 6694. DOI: 10.3390/molecules27196694
  3. Dolgikh O.V., Dianova D.G. Features of hapten specific sensitization and immune status in different student age groups. Rossiiskii immunologicheskii zhurnal, 2020, vol. 23, no. 2, pp. 209–216. DOI: 10.46235/1028-7221-266-FOH (in Russian).
  4. Dolgikh O.V., Dianova D.G. Peculiarities detected in formation of specific hapten sensitization to phenol in children. Health Risk Analysis, 2022, no. 1, pp. 123–129. DOI: 10.21668/health.risk/2022.1.14.eng
  5. Wantke F., Focke M., Hemmer W., Bracun R., Wolf-Abdolvahab S., Götz M., Jarisch R., Götz M. [et al.]. Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students. Allergy, 2000, vol. 55, no. 1, pp. 84–87. DOI: 10.1034/j.1398-9995.2000.00307.x
  6. Vindenes H.K., Svanes C., Lygre S.H.L., Real F.G., Ringel-Kulka T., Bertelsen R.J. Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study. Environ. Health, 2021, vol. 20, no. 1, pp. 81. DOI: 10.1186/s12940-021-00767-2
  7. Alwadi D., Felty Q., Roy D., Yoo C., Deoraj A. Environmental phenol and paraben exposure risks and their potential influence on the gene expression involved in the prognosis of prostate cancer. Int. J. Mol. Sci., 2022, vol. 23, no. 7, pp. 3679. DOI: 10.3390/ijms23073679
  8. Abellan A., Mensink-Bout R., Chatzi L., Duarte-Salles Т., Fernández М.F., Garcia-Aymerich J., Granum B., Jaddoe V. [et al.]. Prenatal exposure to phenols and lung function, wheeze, and asthma in school-age children from 8 European birth cohorts. Eur. Respir. J., 2019, vol. 54, suppl. 63, pp. OA4969. DOI: 10.1183/13993003.congress-2019.OA4969
  9. Tageldin M., Raafat H., Elassal G., Salah Eldin W. Influence of indoor respiratory irritants on the course of bronchial asthma. Egypt. J. Chest Dis. Tuberc., 2014, vol. 63, no. 2, pp. 291–298. DOI: 10.1016/j.ejcdt.2014.01.005
  10. Ao J., Wang Y., Tang W., Aimuzi R., Luo K., Tian Y., Zhang Q., Zhang J. Patterns of environmental exposure to phe-nols in couples who plan to become pregnant. Sci. Total Environ., 2022, vol. 821, pp. 153520. DOI: 10.1016/j.scitotenv.2022.153520
  11. Zamora A.N., Jansen E.C., Tamayo-Ortiz M., Goodrich J.M., Sánchez B.N., Watkins D.J., Tamayo-Orozco J.A., Té-llez-Rojo M.M. [et al.]. Exposure to phenols, phthalates, and parabens and development of metabolic syndrome among Mexican women in midlife. Front. Public Health, 2021, vol. 9, pp. 620769. DOI: 10.3389/fpubh.2021.620769
  12. Wang C., Zhang R., Wei X., Lv M., Jiang Z. Metalloimmunology: the metal ion-controlled immunity. Adv. Immunol., 2020, vol. 145, pp. 187–241. DOI: 10.1016/bs.ai.2019.11.007
  13. Riedel F., Aparicio-Soto M., Curato C., Thierse H.-J., Siewert K., Luch A. Immunological mechanisms of metal allergies and the nickel-specific TCR-pMHC interface. Int. J. Environ. Res. Public Health, 2021, vol. 18, no. 20, pp. 10867. DOI: 10.3390/ijerph182010867
  14. Kolberg L., Forster F., Gerlich J., Weinmayr G., Genuneit J., Windstetter D., Vogelberg C., von Mutius E. [et al.]. Nickel allergy is associated with wheezing and asthma in a cohort of young German adults: results from the SOLAR study. ERJ Open Res., 2020, vol. 6, no. 1, pp. 00178–2019. DOI: 10.1183/23120541.00178-2019
  15. Genchi G., Carocci A., Lauria G., Sinicropi M.S., Catalano A. Nickel: human health and environmental toxicology. Int. J. Environ. Res. Public Health, 2020, vol. 17, no. 3, pp. 679. DOI: 10.3390/ijerph17030679
  16. Li C.-H., Tsai M.-L., Chiou H.-Y.C., Lin Y.-C., Liao W.-T., Hung C.-H. Role of macrophages in air pollution exposure related asthma. Int. J. Mol. Sci., 2022, vol. 23, no. 20, pp. 12337. DOI: 10.3390/ijms232012337
  17. Yang J., Ma Z. Research progress on the effects of nickel on hormone secretion in the endocrine axis and on target organs. Ecotoxicol. Environ. Saf., 2021, vol. 213, pp. 112034. DOI: 10.1016/j.ecoenv.2021.112034
  18. Altaf M.A., Goday P.S., Telega G. Allergic enterocolitis and protein-losing enteropathy as the presentations of manganese leak from an ingested disk battery: a case report. J. Med. Case Rep., 2008, vol. 2, pp. 286. DOI: 10.1186/1752-1947-2-286
  19. Velásquez D., Zamberk P., Suárez R., Lázaro P. Allergic contact dermatitis to manganese in a prosthodontist with orthodontics. Allergol. Immunopathol. (Madr.), 2010, vol. 38, no. 1, pp. 47–48. DOI: 10.1016/j.aller.2009.05.005
  20. Shigematsu H., Kumagai K., Suzuki M., Eguchi T., Matsubara R., Nakasone Y., Nasu K., Yoshizawa T. [et al.]. Cross-Reactivity of Palladium in a Murine Model of Metal-induced Allergic Contact Dermatitis. Int. J. Mol. Sci., 2020, vol. 21, no. 11, pp. 4061. DOI: 10.3390/ijms21114061
  21. Chib S., Singh S. Manganese and related neurotoxic pathways: A potential therapeutic target in neurodegenerative diseases. Neurotoxicol. Teratol., 2022, vol. 94, pp. 107124. DOI: 10.1016/j.ntt.2022.107124
  22. Wu Q., Mu Q., Xia Z., Min J., Wang F. Manganese homeostasis at the host-pathogen interface and in the host immune system. Semin. Cell Dev. Biol., 2021, vol. 115, pp. 45–53. DOI: 10.1016/j.semcdb.2020.12.006
  23. Kimber I., Basketter D.A. Allergic sensitization to nickel and implanted metal devices: a perspective. Dermatitis, 2022, vol. 33, no. 6, pp. 396–404. DOI: 10.1097/DER.0000000000000819
  24. Engeroff P., Caviezel F., Mueller D., Thoms F., Bachmann M.F., Vogel M. CD23 provides a noninflammatory pathway for IgE-allergen complexes. J. Allergy Clin. Immunol., 2020, vol. 145, no. 1, pp. 301–311.e4. DOI: 10.1016/j.jaci.2019.07.045
  25. Caiazzo E., Cerqua I., Turiello R., Riemma M.A., De Palma G., Ialenti A., Roviezzo F., Morello S., Cicala C. Lack of ecto-5'-nucleotidase protects sensitized mice against allergen challenge. Biomolecules, 2022, vol. 12, no. 5, pp. 697. DOI: 10.3390/biom12050697
  26. Pellefigues C. IgE autoreactivity in atopic dermatitis: paving the road for autoimmune diseases? Antibodies (Basel), 2020, vol. 9, no. 3, pp. 47. DOI: 10.3390/antib9030047
  27. Guryanova S.V., Finkina E.I., Melnikova D.N., Bogdanov I.V., Bohle B., Ovchinnikova T.V. How do pollen allergens sensitize? Front. Mol. Biosci., 2022, vol. 9, pp. 900533. DOI: 10.3389/fmolb.2022.900533
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