Safety of antibodies to measles, mumps, rubella and diphtheria in patients with juvenile idiopathic arthritis

Introduction. The issue of protection against vaccinepreventable diseases has acquired new urgency in connection with the decrease in the vaccination rate established by WHO against the background of the COVID-19 pandemic. This creates the conditions for outbreaks and puts patients with immunopathological diseases at particular risk, who are most often not vaccinated from the moment of diagnosis Purpose of the study – to assess the safety of specific antibodies to measles, mumps, rubella and diphtheria in children with JIA, depending on the duration of vaccination, the duration of the disease and the therapy received.

Materials and methods. The vaccination rate of 171 children with juvenile idiopathic arthritis (JIA) aged (11,31±0,31 years) with the duration of the disease at the time of examination was 4,69±0,29 years, who had previously received 1-2 vaccinations against measles, mumps, rubella and 3-6 vaccinations against diphtheria. Antibodies to these infections were determined by ELISA.

Results. 42.1% of children had no protective titers of antibodies to measles, 19,9% – to mumps, 9,4% – to rubella and 16,4% – to diphtheria. Among 93 vaccinated and revaccinated patients, there were no protective titers of antibodies to measles – 40,9% (38 children), mumps – 13,9% (13 people), rubella – 5,4% (5 children), and among 78 vaccinated once, respectively: measles – 43.6% (34 children), mumps – 25.6% (20 children), rubella – 14,1% (11). The level of protection against diphtheria was comparable for those who received 3-5 vaccinations. Depending on the therapy, 3 groups were identified: group 1-71 children received metatrexate and glucocorticosteroids, 2-82 children received modifying anti-rheumatic drugs (DMARD) and 18 children without this therapy (Group 3). Children of the 2nd group were on average older (12,48±0,42 years) than in the 1st and 3rd groups (10,04±0,48 and 10,96±0,96 years, respectively), they had significantly more frequent systemic variant and polyarthritis (64,6% compared to 36,6% and 16,7%, px2<0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. >˂0,001). The number of vaccine doses received by children in all groups before the onset of the disease did not significantly differ. The average level of antibodies to measles in children of group 2 (0,32±0,07 IU/ml) was 2,8 times less than in group 3 and significantly less than in group 1 (0,78±0,16, Pt=0.009), the average value of antibodies to rubella was also significantly less in group 2 (84,48±7,34 IU/ml) than in group 1 (109,73±8,09, Pt=0,022) and in group 3 (120,01±15,42, Pt=0,042). The analysis showed that the safety of antibodies to antigens of live vaccines, especially against measles, is negatively affected by the duration of the disease and the nature of therapy. Children who received combined therapy with anti-TNF, anti-IL-6 and anti-CD-80 drugs had a longer duration of the disease (7,5±0,97 years)=0,00082 compared to those who received only anti-IL-6 (2,9±0,7 years) and antiTNF therapy (6,1±0,5 years) and with a comparable number of vaccine doses received, significantly lower average values of antibodies and a larger number of unprotected ones.

Conclusions. The duration of the disease, the lack of timely age-related revaccinations, as well as the presence of combination therapy aimed at suppressing various mechanisms of the immune response in children with JIA are factors that lead to an increase in the number of unprotected from controlled infections. Immunity to measles suffers the most – 40.9% of revaccinated people are unprotected. 

1. McNally V. V., Henry H. The Effect of the COVID-19 Pandemic on Childhood Immunizations: Ways to Strengthen Routine Vaccination Pediatric Annals. 2020;49(12):e516-e522 https://doi.org/10.3928/19382359-20201115-01

2. Abinun M., J. P. Lane, M. Wood,1 M. Friswell, T. J. Flood, H. E. Foster Infection-Related Death among Persons with Refractory Juvenile Idiopathic//Arthritis Emerging Infectious Diseases www.cdc.gov/eid .Vol. 22, No. 10, October 2016

3. Atzeni F. et al. Infections and biological therapy in patients with rheumatic diseases //The Israel Medical Association journal: IMAJ. – 2016. – T. 18. – №. 3-4. – S. 164-167.

4. 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. Arthritis Rheumatol 2016; 68 (Suppl 10): 4168–9

5. Bijl M., Agmon-Levin N., Dayer J.-M., Israeli E., Gatto M., Shoenfeld Y. //Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefitrisk assessment// Autoimmunity Reviews 2012, 11 r.572–576 doi:10.1016/j.autrev.2011.10.015

6. Wang B., Shao X., Wang D., Xu D., Jin-an Zhang // Vaccinations and Risk of Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Systematic Review and Meta-analysis Autoimmunity Reviews 2017 Jul;16(7):756-765, doi:10.1016/j.autrev.2017.05.012

7. Toussirot É., Bereau M., //Vaccination and Induction of Autoimmune Diseases. // Inflammation & Allergy – Drug Targets, 2015, Volume 14, Issue2 , DOI : 10.2174/1871528114666160105113046

8. Furer V, Rondaan C., Heijstek M W, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases/Ann Rheum Dis 2020;79:39–52. doi:10.1136/annrheumdis-2019-215882

9. Minden K., Speth F., Huppertz H-I, Borte .// Immunization in children and adolescents with rheumatic and musculoskeletal diseases Z Rheumatol . 2014 Dec;73(10):878-89 doi: 10.1007/s00393-014-1396-x

10. Groot N., Heijstek M. W., Wulffraat N. M. //Vaccinations in Paediatric Rheumatology: an Update on Current Developments Curr Rheumatol Rep. 2015; 17(7): Published online 2015 May 30. doi: 10.1007/s11926-015-0519-y

11. Koshcheeva YU.V. Kliniko-immunologicheskaya harakteristika difterijnogo vakcinal’nogo processa i specificheskoe antiteloobrazovanie u detej s revmaticheskimi zabolevaniyami: Avtoref. Diss.kand.med.nauk, SPb, 1998,21 s.

12. Harit S.M. Kliniko-immunologicheskaya harakteristika vakcinal’nogo processa u detej s immunopatologicheskimi zabolevaniyami i porazheniem nervnoj sistemy. Avtoref. Diss dokt.med.naukSPb, 2002,42s.

13. Kostinov M.P. Vakcinoprofilaktika pnevmokokkovoj infekcii i grippa pri autoimmunnyh zabolevaniyah. /Kostinov M.P., Tarasova A.A.//Rukovodstvo dlya vrachej. – M.: MDV; 2009. –252 s.

14. Namazova-Baranova L.S. i dr., Analiz vakcinal’nogo statusa u pacientov s yuvenil’nym idiopaticheskim artritom / Namazova-Baranova L.S., Valieva S.I., Fedoseenko M.V., Novikova D.A., Tkachenko N.E.,. Gajvoronskaya A.G, Broeva M.I., Kalyuzhnaya T.A., SHahtahtinskaya F.CH., Alekseeva E.I., Isaeva K.B. // Pediatricheskaya farmakologiya/2016/ tom 13/ № 4, str 334-339.

15. Heijstek M., GM van Gageldonk P., AM Berbers G., Wulffraat N/M.// 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 Jun;71(6):948-54. doi: 10.1136/annrheumdis-2011-200637.

16. Rollet-Cohen V., Mirete J. , Dingulu G. et al //Suboptimal vaccination coverage of recommended vaccines among French children with recurrent autoinflammatory fever syndromes: a study from the Juvenile Inflammatory Rheumatism cohort //Clin. Rheumatol. 2021$ Jan 13. doi: 10.1007/s10067-020-05553-y. Online ahead of print.

17. Soloshenko M.A.i dr. Profilaktika pnevmokokkovoj infekcii u detej s yuvenil’nym idiopaticheskim artritom. /Soloshenko M.A.Alekseeva E.I., Bzarova T.M., Isaeva K.B., Denisova R.V., Lomakina O.L., Kashchenko E.M., Karasyova A.V. //Voprosy sovremennoj pediatrii /2017/ TOM 16/ № 1, str. 24-28 DOI: 10.15690/vsp.v16i1.1691

18. Akikusa J. D., Crawford N. W. Vaccination in paediatric rheumatology //Current rheumatology reports. – 2014. – T. 16. – №. 8. – S. 432.

19. Heijstek MW, Kamphuis S, Armbrust W, Swart J, Gorter S, de Vries LD, et al. Effects of the live attenuated measlesmumps-rubella booster vaccination on disease activity in patients with juvenile idiopathic arthritis: a randomized trial. JAMA. 2013;309:2449–56

20. Szenborn L. Vaccinations in autoimmune inflammatory rheumatic diseases //Reumatologia. – 2016. – T. 54. – №. 6. – S. 275.

21. N/ M. Alfayadh, P/ J. Gowdie, J.D. Akikusa, M.Lee Easton, J.P. Buttery //Vaccinations Do Not Increase Arthritis Flares in Juvenile Idiopathic Arthritis: A Study of the Relationship between Routine Childhood Vaccinations on the Australian Immunisation //International Journal of Rheumatology / 2020 /Volume 2020 |Article ID 1078914 | https://doi.org/10.1155/2020/1078914

22. Heijstek MW, van Gageldonk PG, Berbers GA, Wulffraat NM.Differences in persistence of measles, mumps, rubella, diphtheria and tetanus antibodies between children with rheumatic disease andhealthy controls: a retrospective crosssectional study. Ann RheumDis. 2012;71(6):948–54.

23. Borte S. et al. Efficacy of measles, mumps and rubella revaccination in children with juvenile idiopathic arthritis treated with methotrexate and etanercept //Rheumatology. – 2009. – T. 48. – №. 2. – S. 144-148.

24. S/ Sousa, A. C. Duarte , I. Cordeiro , J. Ferreira, M.J. Gonçalves, T. Meirinhos , T. Martins Rocha , V. C Romão , M.José Santos /Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature / Acta Reumatol Port . JanMar 2017;42(1):8-16.

25. Uziel Y, Bergonzo VM, Onozo B, et al. Live attenuated vaccines in pediatric rheumatic diseases are safe: multicenter, retrospective data collection. Presented at: Annual European Congress of Rheumatology; June 12-15, 2019; Madrid, Spain. Abstract OP0205.

26. Kapetanovic MC, Saxne T, Jonsson G, et al. Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis. Arthritis Res Ther. 2013;15(5):R171. doi:10.1186/ar4358