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.
Background:Immunosuppressive drugs, decreased vaccine coverage, aberrant immunity might be factors of low anti-vaccine antibodies in JIA patients.Objectives:The study aimed to evaluate risk factors of non-protective levels of antibodies against measles, mumps, rubella, hepatitis B and diphtheria in JIA patients.Methods:A prospective study included 170 children diagnosed with JIA aged 2 to 17 years, who received routine vaccinations against measles, rubella, mumps, diphtheria and hepatitis B. In all patients, the levels of post-vaccination antibodies (IgG) for measles, rubella, mumps, hepatitis B and diphtheria measured with ELISA.Results:Protective level of antibodies were 50% against hepatitis B, 52% diphtheria, 58% measles, 80% mumps, 98%rubella. The best coverage for MMR had patients with enthesytis-related arthritis85%, compare to oligoarthritis70%, polyarthritis69%, systemic arthritis63%. Diphtheria coverage was 50%, 51%, 46%, 63%, respectively. Incomplete MMR vaccination had 39%patients, treated with biologics, 22%with methotrexate and 14%with NSAID(p=0.025), and 61%, 46%, 36% for diphtheria (p=0.021). Incomplete vaccination was a risk factor of non-protective level of antibodies against measles (HR=2.03[95%CI: 1.02; 4.0], p=0.042), parotitis (HR=6.25[95%CI: 2.13; 17.9], p=0.0008) and diphtheria (HR=2.39[95%CI:1.18; 4.85], p=0.016) vaccines. The lowest probability of having a protective level of antibodies was observed in systemic arthritis compared to oligoarthritis (p=0.008) and polyarthritis (p=0.005). JIA patients, with non-protective levels of antibodies against measles, had more extended methotrexate treatment (2.8 [1.3; 6.4] vs 2.2 [0.9; 3.9] years, p<0.05) and increased applying of the biologics (76% vs 52%, p<0.05). Patients treated with biologics had the lowest probability of having protective levels of antibodies against measles, mumps, hepatitis B, and diphtheria than MTX and NSAID. Patients with non-protective antibodies had lower vaccine coverage against mumps (56% vs 67%, p<0.05) and diphtheria (38% vs 61%, p<0.01), longer duration of methotrexate 3.3 [1.4; 6.7] vs 1.8 [1.0; 2.9] years, p<0.01) and biologic treatment 3.1 [1.1; 5.4] vs 0.9 [0.0; 1.9] years, p<0.05) compare to patients with protective levels. The main risk factors to have non-protective levels of antibodies against specific vaccines are in Table 1 below.Table 1.ParametersMeaslesParotitisRubellaDiphtheriaHepatitis BHR (95%CI)рHR (95%CI)рHR (95%CI)рHR (95%CI)рHR (95%CI)РsoJIA, yes1.84 (0.84; 4.03)0.1281.43 (0.53; 3.95)0.4920.99 (0.05; 18.6)0.9952.04 (0.91;4.59)0.082.52 (1.27; 5.0)0.008GCS, yes1.54 (0.91; 2.61)0.1040.31 (0.45;1.84)0.7990.736 (0.11; 4.88)0.7361.89 (1.1; 3.24)0.021.34 (0.77; 2.32)0.295МТХ, yes0.86 (0.39; 1.88)0.7031.55 (0.49; 4.88)0.4531.53 (0.08; 28.64)0.7762.02 (0.71; 5.76)0.1870.6 (0.31; 1.15)0.122Biologics, yes2.02 (1.22; 3.32)0.0061.76 (0.98; 3.15)0.0572.26 (0.5; 9.87)0.2931.67 (0.99; 2.8)0.0531.2 (0.75; 1.92)0.453>1 biologics, consequent, yes1.57 (1.13; 2.2)0.0071.4 (0.93; 2.09)0.1041.82 (0.71; 4.7)0.2131.4 (0.98; 2.0)0.0621.11 (0.78; 1.58)0.572Incomplete vaccination, yes2.02 (1.02; 4.0)0.0426.25 (2.13; 17.9)0.00008na*na*2.39 (1.18; 4.85)0.016na*na*Conclusion:Children with JIA may have lower anti-vaccine antibodies levels and required routine check, especially in children with incomplete vaccination, biologics, systemic arthritis and long-term methotrexate treatment. Funding statement:Footnotes: CI confidence interval, GCS glucocorticosteroids, HR hazard ratio, MTX methotrexate, na not applicable, soJIA systemic onset of juvenile idiopathic arthritis.* Data were not calculated due to a small number of patients with a non-protective level of antibodies against rubella and no patients with incomplete vaccination against hepatitisThis work was supported by the Russian Foundation for Basic Research (grant № 18-515-57001).Disclosure of Interests:None declared
Background:the role of interferon pathways in the pathogenesis of systemic lupus erythematosus (SLE) has been proven over the past years. Existing data suggest that interferon score (IFN I score) may serve as a useful marker of disease activity and patient clinical characteristics.Objectives:to compare characteristics of pediatric SLE patients with high and normal IFN I score.Methods:40 SLE patients (33 girls, 7 boys) under 18 years old were included in the cross-sectional study. In all cases the diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. The data on clinical manifestations, disease activity by SLEDAI and ECLAM, laboratory findings in the onset of the disease and at the moment of interferon signature assessment were evaluated. Interferon signature was assessed by real-time PCR quantitation of 5 IFN I-regulated transcripts; median expression of ≥2 was considered as a threshold. The patients were divided into 2 groups depending on the level of interferon score: high (group1, n=31) and normal (group2, n=9).Results:The mean age of the disease onset was 12 (9.5; 14.0) years. The most common symptoms were skin lesions (85%), arthritis (67.5%), fever (55%), mucosa (45%), CNS (37.5%) and kidney (30%) involvement. Anemia, leukopenia and thrombocytopenia were observed in 62.5%, 27.5% and 50% of cases, while 87.5% and 70% of patients had ANA positivity and dsDNA antibodies at the onset. The comparison between the groups with increased and normal IFN I-signature is presented in Table 1.Table 1.ParametersGroup 1(High IFN-s)Group 2(Normal IFN-s)p-valueGirls, n (%)25 (80.7)8 (88.9)0.567The onset age, years12.0(10.0; 14.0)11.0 (9.0; 13.0)0.353Time to IFN-signature study, months from onset18.3 (7.0; 26.5)0.97 (0.87;1.73)0.987Skin involvement, n (%)12 (38.7)4 (44.4)0.837CNS involvement, n(%)8 (25.8)1 (11.1)0.353Arthritis, n(%)11 (35.5)2 (22.2)0.455Anemia, n(%)9 (29.0)2 (22.200.687Leucopenia, n(%)9 (29.0)1 (11.1)0.274ANA-positivity, n (%)27 (87.1)5 (55.6)0.037anti dsDNA antibodies, n(%)12 (38.7)2 (22.2)0.361Rheumatoid factor, n (%)11 (35.5)0 (0.0)0.036Hypocomplementemia, n (%)18/28 (64.3)2/6 (33.3)0.162Ferritin level, mkg/l112.0 (39.0; 271.0)21.0 (5.3; 23.7)0.0008Hematuria, n (%)10 (32.3)0 (0.0)0.049Proteinuria, n (%)11 (35.5)0 (0.0)0.036SELENA-SLEDAI, points9 (2;15)1 (0; 4)0.073ECLAM, points3.0 (1.0; 6.0)1.0 (0.0; 1.5)0.048Treatment with Rituximab or Cyclophosphamide, n (%)22 (71.0)3 (33.3)0.040GCS dose 0,2 mg/kg achievement for 6 months, n (%)9/21 (42.9)5/6 (83.3)0.080Conclusion:high IFN I-signature correlated with kidney involvement, ANA and RF-positivity, ferritinemia, proteinuria and hematuria. Patients with high IFN I-signature received more aggressive treatment and needed longer glucocorticosteroid (GCS) treatment. More meticulous dynamic evaluation of IFN-signature is needed to clarify its role as a predictive and prognostic marker.Acknowledgements:This work was supported by the RSF grant № 20-45-01005.Disclosure of Interests:None declared.
Background:Patients with juvenile idiopathic arthritis (JIA) may have lower protective levels of anti-vaccine antibodies due to high inflammatory activity, interrupted or incomplete vaccination schedule, and due to using of immune-modulating drugs, e.g. systemic corticosteroids (CS), methotrexate (MTX) and biologics.Objectives:The aim of our study was to find the predictors of low levels of anti-vaccine antibodies in patients with JIA.Methods:In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, hepatitis B, diphtheria and rubella. In all patients the Ig G anti-vaccine antibodies levels were detected with ELISA. In each patient we evaluate the type of the disease (oligoarthritis - 73, polyarthritis - 61, systemic-16 and enthesitis-related arthritis - 20), onset age, presence of uveitis, duration of JIA, treatment with corticosteroids (CS), methotrexate (MTX) and biologics. Data presented with median and 25%-75%.Results:The main demographic characteristics: age of inclusion in the study 11.4 (7.6-14.8) years, disease onset – 6.0 (3.7-9.0) years, disease duration – 3.8 (1.9-6.5) years. Treatment with CS was in 43 (25.3%), MTX in 154 (90,6%) and biologics 82 (48.2%) patients, among them 53 had TNFa-inhibitors. More than 1 biologic consequently received 16/82 (19.5%) patients. Protective levels of anti-measles antibodies was in 98 (57,6%) of all JIA population, anti-parotitis – 136 (80.0%), anti-hepatitis B – 85 (50.0%), anti-diphtheria – 88 (51,7%), anti-rubella – 167 (98.8%). Data of vaccination status and anti-vaccine antibodies levels in the table. In univariate and multivariate regression analysis the main risk factors for anti-measles antibodies levels were MTX using (p=0.045), more than 1 biologics (p=0.0004); for anti-hepatitis B – MTX (p=0.03), for anti-diphtheria antibodies: onset age (p=0.0002), JIA duration (p=0.00007), number vaccine doses (p=0.02), more than 1 biologics (p=0.01); combined treatment with biologics and other drugs (MTX or CS).ParameterNo treatment (n=14)MTT, only(n=74)Biologics±MTT±CS (n=82)P# anti-measels vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-measels IgG, Me/ml0.28 (0.1; 0.6)0.4 (0.1-0.7)0.17 (0.0; 0.29)0.0002Protective anti-measels IgG level, n (%)8 (57)50 (68)40 (49)0.06# anti-parotitis vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-parotitis IgG, Me/ml2.0 (1.2; 4.3)2.8 (1.3; 5.6)2.5 (1.0; 5.1)0.47Protective anti-parotitis IgG level, n (%)12 (86)62 (84)62 (76)0.38# anti-diphtheria vaccine doses5.0 (4.0; 5.0)4.0 (4.0; 5.0)5.0 (4.0; 5.0)0.39Anti-diphtheria IgG, Me/ml0.17 (0.0; 1.2)0.18 (0.0; 0.4)0.1 (0.0; 0.2)0.18Protective anti-diphtheria IgG level, n (%)9 (64)42 (57)37 (45)0.22# anti-hepatitis B vaccine doses3.0 (3.0; 3.0)3.0 (3.0; 3.0)3.0 (3.0; 3.0)0.91Anti-hepatitis B IgG, Me/ml0.56 (0.0; 7.5)11.4 (0.3; 44.8)10.0 (0.0; 44.1)0.08Protective anti-hepatitis B IgG level, n (%)3 (21)40 (54)42 (51)0.08# anti-rubella vaccine doses2.0 (2.0; 2.0)2.0 (1.0; 2.0)2.0 (1.0; 2.0)0.19Anti-rubella IgG, Me/ml121.8(70.0; 200.0)95.6(53.3; 198.2)56.4(37.0; 100.1)0.008Protective anti-rubella IgG level, n (%)14 (100)73 (100)80 (98)0.34Conclusion:MTX, biologics and JIA durations are factors influenced on anti-vaccine antibody level. It is necessary to regularly check the levels of anti-vaccine antibodies, especially anti-measels and anti-diphtheria for creation of the individual vaccination plan for JIA patients, treated with MTX and biologics.Disclosure of Interests:None declared
Background. Patients with juvenile idiopathic arthritis (JIA) may have incomplete vaccination againts different vaccines leads to lower protective levels of anti-vaccine antibodies.The aim of the study – to evaluate the rate and the main factors of incomplete vaccination against measels, parotitis, rubella (MMR), and diphtheria in JIA patients.Methods. In the present study were included data 170 JIA (55 boys and 115 girls) aged from 2 to 17 years, who received scheduled vaccination before the age of 2 years and before JIA onset against measles, parotitis, diphtheria and rubella. Incomplete vaccination means the reduced number of vaccine to age. In all patients the IgG anti-vaccine antibodies levels were detected with ELISA. Data presented with odds ratio ()OR) with 95 confidence interval (CI).Results. Incomplete vaccination against MMR was in 50 (32.5%) of children less than 6 years. Incomplete vaccination against diphtheria was in 6/16 (37.5%) of children less than 6 year, in 53/110 (48.2%) of children aged 6–14 years and in 26/44 (59.1%) of the JIA patients more than 14 years. The main predictors in logistic regression for incomplete vaccination for MMR were: onset age <4 years (OR=12.2 [95% CI: 5.0–28.9]; p=0.0000001), JIA duration >3.1 years (OR=4.4 [95% CI: 2.0–9.9]; p=0.0002), methotrexate duration >3 years (OR=5.7 [95% CI 2.7–12.0]; p=0.0000012); biologic treatment (OR=2.5 [95% CI: 1.3–4.9]; p=0.008) and treatment >1 biologic (OR=3.3 [95% CI: 1.1–10.4]; p=0.002); for diphtheria were: JIA duration >3.1 years (OR=3.4 [95% CI: 1.8–6.5]; p=0.0002), methotrexate duration >2.8 years (OR=4.1 [95% CI: 2.1–8.1]; p=0.00004), biologic treatment (OR=2.4 [95% CI: 1.3–4.4]; p=0.006). In the multiple regression only JIA onset age (p=0.00001) and duration of methotrexate (p=0.003) were predictors of incomplete vaccination against MMR. Methotrexate duration (p=0.005) and biologics treatment (p=0.05) were predictors of incomplete vaccination against diphtheria.Conclusion. The main predictor of incomplete vaccination was younger onset age of JIA. Children received more intensive immunosupression usually have scheduled vaccination rarely which leads to increased number of patients without protective antibody levels. These facts indicate the attitude of physicians parents to vaccination in immunocompromised children. Further investigations required for assessment of safety of vaccinations in children with rheumatic diseases may be a factor for changing this prejudice.
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