Novel mutation in the NRLP3 manifesting as an intermediate phenotype of cryopyrinopathies.

Cryopyrin-associated periodic syndromes (CAPS) are a group of autoinflammatory diseases associated with NLRP3 gain of function mutations. CAPS associated mutations are found predominantly in exon 3. The objective of this study is to describe a new variant on NRLP3 gene and its phenotype. Case report description of a new NRLP3 pathogenic variant and literature case-based search through INFEVERS database. A 21-year old male who presented multiple tonic-clonic seizures on his 3rd day of life. At age 2, he had recurrent central facial palsy, high fever (40 °C), painful and persistent oral ulcers, abdominal pain, nausea and vomiting, and delayed neuropsychomotor development, with polyarthritis in wrists and knees. Over the years, several symptoms were observed: livedo reticularis, Raynaud's phenomenon, positive pathergy test, heat allodynia, extremely painful genital ulcers, and sporadic conjunctivitis. Laboratory studies revealed persistently elevated inflammatory markers and serum amyloid protein A (30 µg/l). The genetic panel for autoinflammatory diseases revealed heterozygous mutation in the NLRP3, (c.2068G > C, p.E690Q) with 0% of frequency in the general population. The patient denies rash and did not have frontal bossing or patellar overgrowth. We found a positive familial history on mother and brother, who carried the same mutation. The patient was started on canakinumab which controlled his symptoms. Currently, 241 missense variants in the NLRP3 have been described. We presented a new mutation in exon 3 of the NRLP3 gene in a patient that fulfills clinical criteria for CAPS who had complete clinical response to Canakinumab, supporting the idea that this mutation is pathogenic.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with juvenile dermatomyositis: a real-world multicentre study.

BACKGROUND: Concerns about the safety and efficacy of vaccines in patients with autoimmune diseases (AID) have led to contradictions and low vaccination coverage in this population, who are at a higher risk of infections, including by human papillomavirus (HPV). Although HPV vaccines have been recommended for immunocompromised patients, there is still a lack of data to support its use for AID patients, such as juvenile dermatomyositis (JDM) patients. The aim of this study was to assess the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in a cohort of JDM patients. METHODS: JDM patients aged from 9 to 20 years and healthy controls (HC) were enrolled to receive a 3-dose schedule of qHPV vaccine from March/2014 to March/2016. Study visits were performed before the first dose, 1 month after the second and third doses, and 6 months after the third dose. Participants completed a diary of possible adverse events for 14 days following each dose of vaccination (AEFV). Disease activity and current therapy were analyzed at each visit for JDM patients. In addition, serum samples from all participants were collected to test antibody concentrations against HPV16 and 18 at each visit. Participant recruitment was conducted in ten Brazilian centres. From 47 eligible JDM patients and 41 HC, 42 and 35, respectively, completed the 3-dose schedule of the vaccine, given that five JDM patients and two HC had received doses prior to their inclusion in the study. RESULTS: The AEFVs presented by the participants were mild and in general did not differ between JDM and HC groups. No severe AEFVs were related to the vaccination. Disease activity was stable, or even improved during the follow-up. One month after the third dose of the vaccine the JDM group presented seropositivity of 100% for HPV16 and 97% for HPV18, similarly to the HC group, who presented 100% for both serotypes (p = 1.000). Six months after the third dose the seropositivity for the patient group was 94% for both HPV types. CONCLUSIONS: The HPV vaccination in this cohort of JDM patients was safe and immunogenic. Since the seropositivity against HPV16 and 18 was very high after the 3-dose schedule, this regimen should be recommended for JDM patients. TRIAL REGISTRATION: Brazilian Clinical Trials Registry, number: RBR-9ypbtf . Registered 20 March 2018 - Retrospectively registered.

Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with childhood systemic lupus erythematosus: a real-world interventional multi-centre study.

OBJECTIVE: This study aimed to assess the safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccination in childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS: Volunteer cSLE patients aged 9-20 years and healthy controls (HC) were enrolled to receive a two- or three-dose qHPV vaccination schedule from March 2014 to March 2016. Study visits were performed before the first dose, one month after the second and third doses and one year after the first dose. In each study visit, disease activity and adverse events following vaccination were analyzed, and a serum sample was collected for testing antibody concentrations. Participant recruitment was conducted in 15 Brazilian paediatric rheumatology units. Of the 256 cSLE patients included, 210 completed the two- or three-dose schedules; 15 had previously received one dose, and 18 had received two doses of the vaccine. The analysis was based on intention-to-treat so that participants who did not complete the entire study protocol were also included. RESULTS: No severe adverse events were related to the vaccination. Disease activity was generally low and remained stable or even improved. The HC presented 100% seropositivity to HPV16 and HPV18, whereas the two- and three-dose cSLE groups presented 93% and 83% versus 97% and 91%, respectively. One year after the first dose, seropositivity of the three-dose cSLE group was 91% to HPV16 and 84% to HPV18. CONCLUSIONS: HPV vaccination in cSLE patients is safe and immunogenic. Since the seropositivity to HPV16 and HPV18 was higher for the three-dose schedule group, this regimen should be recommended for cSLE patients.