Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

AbstractDifferences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.

Download Full-text

Immunogenicity and safety of routine vaccines in children and adolescents with rheumatic diseases on immunosuppressive treatment — a systematic review

European Journal of Pediatrics ◽

10.1007/s00431-021-04283-w ◽

2021 ◽

Author(s):

Michèle Keller ◽

Laure F. Pittet ◽

Petra Zimmermann

Keyword(s):

Systematic Review ◽

Disease Activity ◽

Children And Adolescents ◽

Rheumatic Diseases ◽

Geometric Mean ◽

Immunosuppressive Treatment ◽

Safety Concerns ◽

Vaccine Responses ◽

Autoimmune Rheumatic Diseases ◽

Increased Risk

AbstractThe immunogenicity of vaccines in children with juvenile autoimmune rheumatic diseases (JARDs) can be reduced, there are additional safety concerns around vaccination, and there is a potential for worsening in disease activity. In this systematic review, we summarise studies that investigated the immunogenicity and safety of routine vaccines in children and adolescents with JARD on immunosuppressive treatment. We identified 37 studies investigating 2571 children and adolescents with JARD on immunosuppressive treatment and 4895 control children. Of the 56 geometric mean antibody titres measured, 19 (34%) were lower, six (11%) higher, and 31 (55%) similar; of the 39 seroprotection rates measured, 10 (26%) were lower, two (5%) higher, and 27 (69%) similar; and of the 27 seroconversion rates measured, nine (33%) were lower, two (8%) higher, and 16 (59%) similar in children with JARD on immunosuppressive treatment compared with control children. However, many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls. Subgroup analysis for different types of immunosuppressive treatments was not feasible, as most studies did not report results by treatment. Severe adverse events were reported in 38 children (33 with juvenile idiopathic arthritis, four with systemic lupus erythematosus, and one in a healthy child); most of them were likely not related to the vaccination (e.g. elective hospitalisation or surgery). A worsening in disease activity was reported in 44 (2%) children with JARD; again, many of them were likely not related to the vaccination. There were no safety concerns with live attenuated vaccines; however, only few studies reported results for this.Conclusion: Vaccination in children with JARD on immunosuppressive treatment is safe and should be promoted, especially since these children are at increased risk for infection. The importance for the completion of vaccination schedules should be stressed. Strategies to compensate for the lower vaccine responses, which are found in approximately one-third of these children, include measuring antibody levels to determine the optimal timing for the administration of additional booster doses. What is Known: • Children with juvenile autoimmune rheumatic diseases (JARDs) are at higher risk for infections, due to their underlying disease and their immunosuppressive treatment. • In children with JARD, the immunogenicity of vaccines might be reduced, and concerns about safety or the potential for worsening in disease activity after vaccination exist. What is New: • Our systematic review shows that vaccines in children with JARDs on immunosuppressive treatment are safe and immunogenic. • There are several limitations of the currently published studies, including random timing of measuring vaccine responses and age differences between children with JARD and control groups. Many of the studies were underpowered, and not designed to show non-inferiority between children with JARD and controls.

Download Full-text

POOR ADHERENCE TO DRUG TREATMENT IN CHILDREN AND ADOLESCENTS WITH AUTOIMMUNE RHEUMATIC DISEASES

Revista Paulista de Pediatria ◽

10.1590/1984-0462/;2019;37;2;00019 ◽

2019 ◽

Vol 37 (2) ◽

pp. 138-139

Author(s):

Clovis Artur Silva

Keyword(s):

Drug Treatment ◽

Children And Adolescents ◽

Rheumatic Diseases ◽

Poor Adherence ◽

Autoimmune Rheumatic Diseases

Download Full-text

EVALUATION OF ANTI-DFS70 ANTIBODIES PRE-ABSORPTION PROTOCOL FOR ANA-IIF HEP-2 TESTING IN THE DIAGNOSTIC APPROACH OF SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASES

10.26226/morressier.56e174dbd462b8028d88ad4c ◽

2016 ◽

Author(s):

Alexandra Tsirogianni

Keyword(s):

Rheumatic Diseases ◽

Diagnostic Approach ◽

Autoimmune Rheumatic Diseases

Download Full-text

TNF-α -308 G>A and IL10 -1082A>G polymorphisms as potential risk factors for lymphoproliferative disorders in autoimmune rheumatic diseases

Egyptian Journal of Medical Human Genetics ◽

10.1186/s43042-019-0043-0 ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Manal Y. Tayel ◽

Aida Nazir ◽

Ibtessam M. Abdelhamid ◽

Myriam A. S. Helmy ◽

Nadia E. Zaki ◽

...

Keyword(s):

Risk Factors ◽

Rheumatic Diseases ◽

Lymphoproliferative Disorders ◽

Group Iii ◽

Autoimmune Rheumatic Diseases ◽

Group I ◽

Tnf Α ◽

Ifn Γ ◽

Tgf Β1 ◽

Distribution Frequency

Abstract Background Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α -308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs -1082 A>G, -819T>C, and -592A>C; IL-6 -174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCR-sequence-specific primer (PCR-SSP). Results ARD+LPD patients had significantly higher frequency of TNF-α -308A allele and AA+AG genotype (high TNF-α producers) and IL-10 -1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion The significantly increased frequency of the high-TNF-α- and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

Download Full-text

Waning antibody responses in COVID-19: what can we learn from the analysis of other coronaviruses?

Infection ◽

10.1007/s15010-021-01664-z ◽

2021 ◽

Author(s):

Ali Hamady ◽

JinJu Lee ◽

Zuzanna A. Loboda

Keyword(s):

Cross Reactivity ◽

Antibody Responses ◽

The Novel ◽

Incidence And Mortality ◽

Antibody Titres ◽

Human Coronaviruses ◽

Public Health Strategies ◽

Antibody Dynamics

Abstract Objectives The coronavirus disease 2019 (COVID-19), caused by the novel betacoronavirus severe acute respiratory syndrome 2 (SARS-CoV-2), was declared a pandemic in March 2020. Due to the continuing surge in incidence and mortality globally, determining whether protective, long-term immunity develops after initial infection or vaccination has become critical. Methods/Results In this narrative review, we evaluate the latest understanding of antibody-mediated immunity to SARS-CoV-2 and to other coronaviruses (SARS-CoV, Middle East respiratory syndrome coronavirus and the four endemic human coronaviruses) in order to predict the consequences of antibody waning on long-term immunity against SARS-CoV-2. We summarise their antibody dynamics, including the potential effects of cross-reactivity and antibody waning on vaccination and other public health strategies. At present, based on our comparison with other coronaviruses we estimate that natural antibody-mediated protection for SARS-CoV-2 is likely to last for 1–2 years and therefore, if vaccine-induced antibodies follow a similar course, booster doses may be required. However, other factors such as memory B- and T-cells and new viral strains will also affect the duration of both natural and vaccine-mediated immunity. Conclusion Overall, antibody titres required for protection are yet to be established and inaccuracies of serological methods may be affecting this. We expect that with standardisation of serological testing and studies with longer follow-up, the implications of antibody waning will become clearer.

Download Full-text

P052 Leflunomide and severe COVID-19 outcome: a cautionary observation from the COVID-19 Scottish Registry of Autoimmune Rheumatic Diseases (SCAR-19)

Rheumatology ◽

10.1093/rheumatology/keab247.049 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Maira Karabayas ◽

James Brock ◽

Gillian Fordyce ◽

Neil Basu

Keyword(s):

Rheumatic Diseases ◽

Clinical Characteristics ◽

National Registry ◽

Favourable Outcome ◽

Non Invasive ◽

Autoimmune Rheumatic Diseases ◽

Non Invasive Ventilation ◽

Pcr Diagnosis ◽

Related Symptom ◽

Disease Modifying

Abstract Background/Aims Leflunomide, a conventional disease modifying drug (csDMARD), is used in a variety of autoimmune rheumatic diseases (ARD) due to its immunomodulating, immunosuppressive and antiproliferative properties. This agent does however confer a greater infection risk and, due to its long half-life, drug washout procedures are often advised in the context of serious infections. Interestingly, Leflunomide is currently being tested as a potential therapy for COVID-19 in the general population. It is unknown whether leflunomide therapy is associated with a poor or favourable outcome among ARD patients infected with COVID-19. Methods A Scottish-wide registry was rapidly developed in March 2020. Clinical characteristics and outcomes of infected cases were collated across all Scottish health boards. Eligible patients included any adult leflunomide treated ARD patients with a confirmed (clinically or PCR) diagnosis of COVID-19. Results Of the 69 cases included in the registry, n = 4 were treated with leflunomide (75% female; mean age 61, SD 4.2). N = 2 were treated with combination baricitinib or hydroxychloroquine respectively, whilst n = 1 received recent corticosteroid therapy (intramuscular Kenalog). Comorbidities observed in this sub-cohort include diabetes mellitus n = 3, hypertension n = 2, cardiovascular disease n = 1, lung disease n = 1 and latent TB n = 1. At presentation, all patients (n = 4) experienced the established COVID-19 related symptom triad of dyspnoea, cough and fever and promptly developed acute respiratory syndrome. Diarrhoea was also recorded in n = 2 and constitutional upset n = 3. All patients suffered a serious COVID-19 disease outcome (defined as a requirement of invasive or non-invasive ventilation (n = 4) and/ or death (n = 2). P052 Table 1:Patient demographics, clinical characteristics and outcomesPatient 1Patient 2Patient 3Patient 4Age58635766SexFemaleFemaleMaleFemaleRheumatic diagnosisRheumatoid arthritisPsoriatic arthritisPsoriatic arthritisRheumatoid ArthritisComorbiditiesDiabetesHypertension Diabetes COPDNilIschaemic heart disease Hypertension Diabetes Latent TBClinical presentationDyspnoea Cough Fever Confusion Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetDyspnoea Cough Fever Constitutional upsetDyspnoea Cough Fever Diarrhoea Constitutional upsetAdditional csDMARD*NilNilNilHydroxychloroquinebDMARD**/ tsDMARD***BaricitinibNilNilNilSteroid therapyNilNilNilIM KenalogInvasive or non-invasive ventilationYesYesYesYesDeathNoNoYesYes* conventional disease modifying drug,**biologic disease modifying drug,***targeted synthetic disease modifying drug. Conclusion Preliminary data from this Scotland-wide registry has identified only a small number of leflunomide treated ARD patients infected with COVID-19. However, it is concerning that all cases experienced a serious outcome. Given the relatively infrequent prescription of this drug, combining similar national registry data is necessary to ensure this observation is not spurious. If confirmed, leflunomide washout procedures should be encouraged among such patients when they first present with COVID-19. Disclosure M. Karabayas: None. J. Brock: None. G. Fordyce: None. N. Basu: None.

Download Full-text