Measles-specific antibodies loss after a single dose of MMR vaccine in children with oligo-articular JIA on methotrexate treatment: a single-center case-controlled study.

Novel treatments have revolutionized the care and outcome of patients with juvenile idiopathic arthritis (JIA). Patients with rheumatic diseases are susceptible to infections, including vaccine preventable ones, due to waning immunity, failing immune system and immunosuppressive treatment received. However, data regarding long-term immunological memory and response to specific vaccines are limited. Assessment of the impact of methotrexate (MTX) treatment on measles-specific-IgG titers, in children with oligo-JIA previously vaccinated with Measles Mumps Rubella (MMR) vaccine (1 dose); by evaluating the persistence of antibodies produced after measles vaccination while on immunomodulating treatment at 0, 12 and 24 months. Single-center controlled study including 54 oligo-JIA patients and 26 healthy controls. Seroprotection rates and measles-specific-IgG titers were measured by ELISA and were expressed as GMCs (Geometric Mean Concentrations).The two groups had similar demographic characteristics, vaccination history and immunization status. Seroprotection rates were adequate for both groups. Nonetheless, measles GMCs were significantly lower in the oligo-JIA compared to the control group at one (p = 0.039) and two years' follow-up (p = 0.021). Children with oligo-JIA on MTX treatment appeared to have lower measles-specific-IgG titers. Further studies are required to assess the long-term immunity conveyed by immunizations given at an early stage in children with rheumatic diseases on synthetic Disease Modifying Antirheumatic Drugs (sDMARDs) and to assess the need for booster doses to subjects at risk.

Immunogenicity 6 months post COVID-19 mRNA vaccination among adolescents with juvenile idiopathic arthritis on treatment with TNF inhibitors.

OBJECTIVES: Mass vaccination is the most effective strategy for controlling the COVID-19 pandemic. This study aimed to evaluate the 6-month immunogenicity after BNT162b2-COVID-19 vaccination in adolescents with JIA on TNFi treatment. METHODS: This single-centre study included adolescents with JIA treated with TNFi for at least 18 months. Patients received two doses of COVID-19 vaccine (Pfizer-BioNTech) from 15 April to 15 May 2021. Quantitative measurement of IgG antibodies to SARS-CoV-2-spike-protein-1 was performed at 1, 3 and 6 months post-vaccination. RESULTS: Overall, 21 adolescents with JIA in clinical remission at the time of vaccinations were enrolled. None of them discontinued TNFi/MTX treatment at the time of vaccine administration or during the follow-up period. All patients developed a sustained humoral response against SARS-CoV-2 at 1 and 3 months after vaccination (P < 0.05). The antibody levels decreased significantly at 6 months post-vaccination (P < 0.01). The type of JIA did not reveal any differences in the humoral response at 3 (P = 0.894) or 6 months post-vaccination (P = 0.72). No difference was detected upon comparison of the immunogenicity between the different treatment arms (adalimumab vs etanercept) at 3 (P = 0.387) and 6 months (P = 0.526), or TNFi monotherapy vs combined therapy (TNFi plus methotrexate) at 3 (P = 0.623) and 6 months (P = 0.885). CONCLUSIONS: Although mRNA vaccines develop satisfactory immunogenicity at 1 month and 3 months post-vaccination in adolescents with JIA on TNFi, SARS-CoV-2 antibody titres decrease significantly overtime, remaining at lower levels at 6 months. Further collaborative studies are required to determine long-term immunogenicity, real duration of immune protection and the need for a booster vaccine dose.

A National Survey Across Primary Care Pediatricians Regarding Immunization Views and Practices in Children With Rheumatic Diseases.

METHODS: Cross-sectional survey conducted with an anonymous questionnaire of 34 items distributed to pediatricians via an online platform. Four hundred questionnaires were sent, and 256 were returned and analyzed using STATA 13. Data collection included demographics, questions on knowledge, perceptions, and opinions, as well as advice given to families. RESULTS: The majority of doctors felt that vaccination in children with RDs is essential. Responders were using a variety of guidelines to reach a clinical decision. Fifty percent were hesitant to adhere to the national vaccination scheme without expert input. Reasons were as follows: not convinced from current literature that the vaccine is safe (32%), afraid to cause disease flare (43%), and unable to deal with parental concerns/refusal (54%). Twelve percent of responders felt that the RD may have been triggered by a vaccine. The majority (82%) of doctors were pro annual influenza vaccination. Seventy percent of doctors were keener to administer booster doses rather than primary ones. CONCLUSIONS: Variation in opinion and clinical practice exists. Overall, although general pediatricians are informed regarding efficacy and adverse effects of immunizations in patients with RDs, there are steps to be made from principle to practice. Vaccinating these children is of vital importance, and primary care pediatricians should be updated regarding existing guidelines referring to this field.

Diagnosis and Management of a Young Girl With Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) Linked to a Novel Mutation.

A nine-year-old girl with a two-month history of fever and generalized malaise, along with intermittent abdominal pain, immigrant myalgia, throat pain, anorexia, and long-standing failure to thrive, was admitted to our department for further investigation and treatment. Detailed medical history revealed recurrent inflammation attacks from a very young age and a heavily burdened family history. Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) was highly suspected. Genetic screening was performed and several members of the family were found to be carriers of C73Y mutation in exon 3, which is a novel tumor necrosis factor superfamily receptor 1A (TNFRSF1A) mutation. The girl was treated with an interleukin-1ß inhibitor, canakinumab, which induced immediate and complete remission of disease that interestingly lasted for a long period even after medication discontinuation.

Molecular and clinical spectrum of four pedigrees of TRAPS in Greece: results from a national referral center.

OBJECTIVE: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominantly inherited autoinflammatory disease caused by mutations of the TNFRSF1A gene. To address the association between TNFRSF1A mutations and clinical phenotype, we analyzed four pedigrees of TRAPS patients. METHODS: Four Greek patients with TRAPS-like clinical features were screened for TNFRSF1A mutations by sequencing exons 2, 3 and 4. Following positive testing, twenty-two members of their families were also genetically and clinically screened. RESULTS: Twenty-six members of four unrelated Greek families were investigated. The C73Y (c.305G>A) mutation of the TNFRSF1A gene was identified in five patients, with two of the five carrying a concomitant R92Q variation. We also identified seven C73W (c.306C>G), two T50M (c.236C>T) and seven R92Q (c.362G>A) carriers. Symptoms varied and the C73Y, C73W and T50M mutations were associated with the most severe clinical manifestations. The R92Q phenotype ranged from asymptomatic to mild disease. Molecular modelling linked pathogenicity with aberrant TNFRSF1A disulphide bond formation. CONCLUSION: In this first pedigree analysis of TRAPS in Greece, we identified the rare C73Y TNFRSF1A mutation. A wide clinical spectrum was observed with the C73Y, C73W and T50M mutations that affect TNFRSF1A disulphide bonds and are associated with worse symptoms.

Immunogenicity and side-effects of the inactivated hepatitis A vaccine in periodic fever, aphthous stomatitis, pharyngitis, and adenitis patients.

The aim of this study was to compare the immunogenicity and side-effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV-immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side-effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well-tolerated and effective in children with PFAPA.

Immunogenicity and safety of the inactivated hepatitis A vaccine in children with juvenile idiopathic arthritis on methotrexate treatment: a matched case-control study.

OBJECTIVES: To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. METHODS: Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. RESULTS: 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated. CONCLUSIONS: Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.

Detection of acquired hemoglobinopathy in children with hematological malignancies at disease onset: results form a national referral centre.

Abnormal hemoglobin synthesis is usually inherited but may also arise as a secondary manifestation of a hematological neoplasia. The objective of this study is to identify the presence of acquired hemoglobinopathy in children diagnosed with hematological malignancies and compare these against healthy controls. Prospective matched case-control study held from 2010 to 2012. For each patient with hematological malignancy two healthy controls matched on gender, age and race were recruited. Patients with other co-morbidities were excluded. All samples underwent supravital staining and high-performance liquid chromatography (HPLC) electrophoresis. Following identification of abnormal results, molecular genetic testing for all α- and ß-thalassemia mutations prevalent in the Greek population was performed. Other causes of anemia were ruled out based on specific testing. A total of 44 (32 males) patients with a mean age of 7.1 years were enrolled in the study. Hematological disorders included acute lymphocytic leukemia (24), acute myeloid leukemia (8), non-Hodgkin lymphoma (8), Hodgkin disease (3), and Langerhans cell histiocytosis (1). Following exclusion of congenital hemoglobinopathies, atypical HPLC electrophoretic findings persisted in 18.1 % of the patient group, compared to 0 % in the control group (p < 0.001). The patient group showed marked microcytic anemia (p < 0.01) and detection of small inclusions (p = 0.034) on supravital staining. Comparison of the HPLC findings between the groups demonstrated significantly lower percentages of HbA (p = 0.02), normal HbA2 and higher percentage of fast moving Hb bands (p = 0.04) in the patient group. Interestingly, the majority of these patients belonged to the high-risk group. Acquired hemoglobinopathy is recognized in adult patients. This is a novel study describing evidence of abnormal erythropoiesis in children with hematological malignancies and in particular those classified as high-risk cancer patients according to international criteria.