Preservation of Postvaccinal Immunity to Measles, Rubella, Parotitis, Hepatitis B and Diphtheria in Patients With Juvenile Idiopathic Arthritis Who Undergone Planned Immunization Under the Age of Two: Preliminary Results of Cross-Sectional Study

Background. Patients with juvenile idiopathic arthritis (JIA) can have low levels of antibodies to vaccine antigens due to immunologic features of the main disease, disruptions in vaccination schedule and immunosuppressive drugs administration

Objective. The aim of the study was to examine the status of postvaccinal immunity and determine the factors associated with preservation of protective level of antibodies in patients with JIA.

Methods. This cross-sectional study included patients with JIA at the age from 2 to 17 years old vaccinated under the age of two (before JIA) against measles, rubella, parotitis, hepatitis B and diphtheria. Levels of IgG to vaccine antigens were measured by enzyme immunoassay. The minimum protective level of anti-measles IgG was esteemed as 0.18 IU/ml, antibodies to rubella — 10 IU/ml, for parotitis — COI > 1.0, for hepatitis B — 10 mIU/ml, antibodies to diphtheria — 0.09 IU/ml.

Results. The study included 90 patients with JIA (71% of girls) at the age (median) 11.3 (7.5; 14.9) years. The age of JIA manifestation was 6.0 (4.0; 8.0) years, disease duration — 4.0 (2.0; 7.3) years. Glucocorticosteroids administration in anamnesis or at study entry was recorded in 24/88 (27%) patients, methotrexate — 81/88 (92%), genetically engineered biologic drugs — 54/89 (61%). Protective level of antibodies to measles virus was revealed in 45 (50%) children with JIA, to rubella virus — in 88 (98%), to parotitis — in 68 (76%), to hepatitis B — in 49 (54%), to diphtherial anatoxin — in 45 (50%). The decrease of postvaccinal immunity level was associated with JIA duration and glucocorticosteroids administration (against diphtheria) duration, as well as drop-out immunization (against measles).

Conclusion. Major part of children with JIA have no protection against measles, parotitis, hepatitis B or diphtheria. High risk of progression of such vaccine-preventable diseases in these children demands development of individual programs of immunization.

1. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007; 369(9563):767-778. doi: 10.1016/S0140-6736(07)60363-8.

2. Cassidy JT, Petty RE. Textbook of pediatric rheumatology. Elsevier Saunders; 2005. 792 p.

3. Beukelman T, Xie F, Chen L, et al; SABER Collaboration. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthrit Rheum. 2012;64(8):2773-2780. doi: 10.1002/art.34458.

4. Salvana EM, Salata RA. Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev. 2009;22(2):274-290. doi: 10.1128/CMR.00040-08.

5. Giancane G, Swart J, Bovis F, et al. Risk of infections in juvenile idiopathic arthritis patients treated with biologic agentsand/or methotrexate: results from pharmachild registry. Abstract number: 3116. Available from: https://acrabstracts.org/abstract/risk-of-infections-in-juvenile-idiopathic-arthritis-patients-treated-with-biologic-agentsandor-methotrexate-results-from-pharmachild-registry/.

6. Abinun M, Lane JP, Wood M, et al. Infection-related death among persons with refractory juvenile idiopathic arthritis. Emerg Infect Dis. 2016;22(10):1720-1727. doi: 10.3201/eid2210.151245.

7. Castillo RD, De la Pena W, Marzan KA. Diagnosis and management of infectious complications of childhood rheumatic diseases. Curr Rheumatol Rep. 2013;15(4):322. doi: 10.1007/s11926-013-0322-6.

8. Heijstek MW, Ott de Bruin LM, Bijl M, et al.; EULAR. EULAR recommendations for vaccination in paediatric patients with rheumatic diseases. Ann Rheum Dis. 2011;70(10):1704-1712. doi: 10.1136/ard.2011.150193.

9. Heijstek MW, van Gageldonk PG, Berbers GA, et al. Differences in persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between children with rheumatic disease and healthy controls: a retrospective cross-sectional study. Ann Rheum Dis. 2012;71(6):948-954. doi: 10.1136/annrheumdis-2011-200637.

10. Petty RE, Southwood TR, Manners P et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390-392.

11. MU 3.1.2943-11 Organizatsiya i provedeniye serologicheskogo monitoringa sostoya-niya kollektivnogo immuniteta k infektsiyam, upravlyayemym sredstvami spetsificheskoy profilaktiki (difteriya, stolbnyak, koklyush, kor’, krasnukha, epidemicheskiy parotit, poliomiyelit, gepatit V). (In Russ). Доступно по: http://docs.cntd.ru/document/1200088401. Ссылка активна на 12.04.2019.

12. Koshcheeva IV, Kharit SM, Kalinina NM. Specific features of diphtheria vaccinal process in children with rheumatic diseases. Journal of microbiology, epidemiology, and immunobiology. 2001;(6): 44-49. (In Russ).

13. Kharit SM. Vaktsinoprofilaktika detey s immunopatologicheskimi zabolevaniyami. Farmateka. 2003;(2):33-37. (In Russ).

14. Heijstek MW, Kamphuis S, Armbrust W, et al. Effects of the live attenuated measles-mumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial. JAMA. 2013;309(23):2449-2456. doi: 10.1001/jama.2013.6768.

15. Kliniko-laboratornaya diagnostika korevoy infektsii. Informatsionnoye pis'mo №16. Moscow; 2002. 15 р. (In Russ).

16. Zargar'yants AI, YAkovleva IV, Selezneva TS, et al. Dlitel'nost' i napryazhennost' postvaktsinal'nogo gumoral'nogo immuniteta k virusam kori, parotita i krasnukhi. Epidemiologiya i vaktsinoprofilaktika. 2005;(5):15-19. (In Russ).

17. Shulgina NI, Stasenko VL. Assessment of duration and intensity of post-vaccination humoral immunity to hepatitis B patients decreed groups. Epidemiologiya i vaktsinoprofilaktika. 2011;(1):68-73. (In Russ).

18. Yakimova TN. Epidemiologicheskiy nadzor za difteriyey v Rossii v period regis-tratsii edinichnykh sluchayev zabolevaniya. [dissertation abstract] Moscow; 2015. 22 р. (In Russ). Доступно по: https://search.rsl.ru/ru/record/01006646046. Ссылка активна на 14.06.2019.

19. Kasapcopur O, Cullu F, Kamburoglu-Goksel A, et al. Hepatitis B vaccination in children with juvenile idiopathic arthritis. Ann Rheum Dis. 2004;63(9):1128-1130. doi: 10.1136/ard.2003.013201.

20. Borte S, Liebert UG, Borte M, et al. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept. Rheumatology (Oxford). 2009;48(2):144-148. doi: 10.1093/rheumatology/ken436.

21. Stoof SP Heijstek MW, Sijssens KM, et al. Kinetics of the long-term antibody response after meningococcal C vaccination in patients with juvenile idiopathic arthritis: a retrospective cohort study. Ann Rheum Dis. 2014;73(4):728-734. doi: 10.1136/annrheumdis-2012-202561.

22. Farmaki E, Kanakoudi-Tsakalidou F, Spoulou V, et al. The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Vaccine. 2010;28(31):5109-5113. doi: 10.1016/j.vaccine.2010.03.080.

23. Groot N, Heijstek MW, Wulffraat NM. Vaccinations in paediatric rheumatology: an update on current developments. Curr Rheumatol Rep. 2015;17(7):46. doi: 10.1007/s11926-015-0519-y.

24. Miyamoto M, Ono E, Barbosa C, et al. Vaccine antibodies and T- and B-cell interaction in juvenile systemic lupus erythematosus. Lupus. 2011;20(7):736-744. doi: 10.1177/0961203310397409.

25. Ogimi C, Tanaka R, Saitoh A, Oh-Ishi T. Immunogenicity of influenza vaccine in children with pediatric rheumatic diseases receiving immunosuppressive agents. Pediatr Infect Dis J. 2011;30(3): 208-211. doi: 10.1097/INF.0b013e3181f7ce44.