scholarly journals Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases

RMD Open ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. e001898
Author(s):  
Cristiana Sieiro Santos ◽  
Sara Calleja Antolin ◽  
Clara Moriano Morales ◽  
Juan Garcia Herrero ◽  
Elvira Diez Alvarez ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Rheumatic Diseases ◽  
Cellular Responses ◽  
Phase Iii ◽  
Inflammatory Rheumatic Diseases ◽  
Vaccine Responses ◽  
Immune Mediated ◽  
Antibody Titres ◽  
Immunosuppressed Patients

BackgroundPatients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines.AimsTo fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine’s immunogenicity.MethodsHumoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls.ResultsPatients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines.ConclusionsPatients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.

BARICITINIB: NEW PHARMACOTHERAPY OPTIONS FOR RHEUMATOID ARTHRITIS AND OTHER IMMUNE-MEDIATED INFLAMMATORY RHEUMATIC DISEASES

2020 ◽  
Vol 58 (3) ◽  
pp. 304-316
Author(s):  
E. L. Nasonov ◽  
A. M. Lila
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatic Diseases ◽  
Janus Kinase ◽  
Inflammatory Rheumatic Diseases ◽  
Jak Inhibitors ◽  
Oral Medications ◽  
Immune Mediated ◽  
Wide Range ◽  
Promising Area ◽  
Medical Advances

Deciphering the mechanisms of the pathogenesis of immune-mediated inflammatory rheumatic diseases (IMIRDs) in conjunction with designing a wide range of biological agents is one of the major medical advances in the 21st century. A new promising area of pharmacotherapy for IMIRDs is associated with the design of the so-called targeted oral medications that primarily include Janus kinase (JAK) inhibitors. The review presents new data on the efficacy and safety of the new JAK inhibitor baricitinib in treating rheumatoid arthritis and other IMIRDs.

scholarly journals Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

2021 ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Children develop strong and sustained cross-reactive immune responses against Spike protein following SARS-CoV-2 infection, with enhanced recognition of variants of concern

2021 ◽  
Author(s):  
Alexander C. Dowell ◽  
Megan S. Butler ◽  
Elizabeth Jinks ◽  
Gokhan Tut ◽  
Tara Lancaster ◽  
...  
Keyword(s):  
Immune Responses ◽  
Natural Infection ◽  
Humoral Response ◽  
Cellular Responses ◽  
Paediatric Population ◽  
Spike Protein ◽  
High Antibody ◽  
Antibody Titres ◽  
Clinical Protection ◽  
Th1 Cytokine

AbstractSARS-CoV-2 infection is generally mild or asymptomatic in children but the biological basis for this is unclear. We studied the profile of antibody and cellular immunity in children aged 3-11 years in comparison with adults. Antibody profiles in children were strong, with high titres against Spike protein and receptor binding domain (RBD). SARS-CoV-2 seroconversion in children strongly boosted antibody responses against seasonal beta-coronaviruses, partly through cross-recognition of the S2 domain, indicating a broad humoral response that was not seen in adults. T cell responses against Spike were also >2-fold higher in children compared to adults and displayed a strong Th1 cytokine profile. SARS-CoV-2 Spike-reactive cellular responses were present in more than half the seronegative children, indicating pre-existing cross-reactive responses or prior sensitization against SARS-CoV-2. Importantly, all children retained high antibody titres and cellular responses for more than 6 months after infection whilst relative antibody waning was seen in adults. Significantly Children at this timepoint also had high antibody titres to B1.1.7, B1.351 and P1 variants. Children thus distinctly generate robust, cross-reactive and sustained immune responses after SARS-CoV-2 infection, with focussed specificity against Spike protein. These observations demonstrate several novel features of SARS-CoV-2-specific immune responses in children and may provide insights into relative clinical protection in this group. Such information on the profile of natural infection will help to guide the introduction of vaccination regimens into the paediatric population.

scholarly journals Coronavirus disease 2019 (COVID-19) and immune-mediated inflammatory rheumatic diseases: at the crossroads of thromboinflammation and autoimmunity

2020 ◽  
Vol 58 (4) ◽  
pp. 353-367
Author(s):  
E. L. Nasonov ◽  
T. V. Beketova ◽  
T. M. Reshetnyak ◽  
A. M. Lila ◽  
L. P. Ananieva ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Complement System ◽  
Vascular Endothelial Cells ◽  
Basic Mechanism ◽  
Pathological Process ◽  
Human Organism ◽  
Inflammatory Rheumatic Diseases ◽  
Irreversible Damage ◽  
Immune Mediated ◽  
The Complement System

Inflammation and coagulation are key basic mechanism of protection against all potentially pathogenic mechanical and biological factors targeting human organism from inner and outer environment. On the other hand, uncontrolled inflammation results in hypercoagulation, inhibition of anticoagulation and alteration of mechanisms responsible for resolution of inflammation, while production of “procoagulant” mediators (thrombin, tissue factor and others), activation of platelets and of vascular endothelial cells maintains inflammation. All factors taken together serve as the basis for a pathological process called thromboinflammation or immunothrombosis. Currently thromboinflammation is considered in the broad sense as a universal pathogenetic mechanism of numerous widespread acute and chronic conditions, including immune-mediated (autoimmune) inflammatory rheumatic diseases, oftentimes complicated by severe irreversible damage to vital organs. Thromboinflammation gained specific attention during СОVID-19 (coronavirus disease 2019) pandemic, caused by SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). COVID-19 is considered currently as systemic thromboinflammation syndrome, manifesting via generalized thrombosis of arterial and venous macro- and microvasculature, termed as COVID-19-coagulopathy. The paper discusses common pathogenetic coagulopathy mechanisms in COVID-19 and immune-mediated (autoimmune) inflammatory rheumatic diseases (IMRDs), associated with overproduction of antiphospholipid antibodies, activation of the complement system, and dis-regulated synthesis of proinflammatory cytokines, etc. Delineating the autoimmune subtype of thromboinflammation, identification of genetic (i.e., genes encoding the complement system and others) and molecular-biologic biomarkers associated with higher occurrence of COVID-19-coagulopathy are the most relevant undertakings for the current practice. Gaining insights into mechanisms of thromboinflammation and converting them into potential pharmacotherapies of IMDs would facilitate and accelerate the drafting of effective therapeutic strategies for COVID-19. 

Reproductive function in women with immune-mediated inflammatory rheumatic diseases

2019 ◽  
Vol 10_2019 ◽  
pp. 51-59
Author(s):  
Vlasova G.A. Vlasova ◽  
Perminova S.G. Perminova ◽  
Kosheleva N.M. Kosheleva ◽  
Nazarenko T.A. Nazarenko ◽  
◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Reproductive Function ◽  
Inflammatory Rheumatic Diseases ◽  
Immune Mediated

scholarly journals Activated PIK3CD drives innate B cell expansion yet limits B cell–intrinsic immune responses

2018 ◽  
Vol 215 (10) ◽  
pp. 2485-2496 ◽  
Author(s):  
Michelle N. Wray-Dutra ◽  
Fahd Al Qureshah ◽  
Genita Metzler ◽  
Mohamed Oukka ◽  
Richard G. James ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Plasma Cells ◽  
Recurrent Infection ◽  
Vaccine Responses ◽  
And Function ◽  
Natural Igm ◽  
The Impact

Activated PI3K-delta syndrome (APDS) is an immunodeficiency caused by gain-of-function mutations in PIK3CD. This disease exhibits complex immune phenotypes including increased IgM, recurrent infection, and impaired vaccine responses. To better understand the impact of B cells in this disease, we generated an inducible model of the common APDS mutation (hPIK3CD-E1021K; referred to as aPIK3CD) and intercrossed these mice with B cell–specific Cre models. Mb1-aPIK3CD mice exhibited bone marrow B lymphopenia and, conversely, expansion of the peripheral innate B1a and MZ B cell compartments. aPIK3CD B cells manifest increased pS6 and increased survival at several stages, without alterations in cycling, and baseline increases in plasma cells, natural IgM, and IgG3. Finally, Mb1-aPIK3CD mice exhibited blunted T cell–independent immune responses, and both AID- and CD21-aPIK3CD mice displayed reduced class-switched antibodies following T cell–dependent immunization. Thus, aPIK3CD alters B cell development and function and is counter-productive during immune responses, providing insight into B cell–intrinsic contributions to the APDS phenotype.

scholarly journals Autoimmune inflammatory syndrome induced by adjuvants (silicone breast implants and lip fillers)

2021 ◽  
Vol 72 (1) ◽  
pp. 1-5
Author(s):  
Božidar Pocevski ◽  
Slavica Pavlov-Dolijanović
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Breast Implants ◽  
Inflammatory Rheumatic Diseases ◽  
Silicone Breast Implants ◽  
Immune Mediated ◽  
Systemic Symptoms ◽  
Patients Experience ◽  
Inflammatory Syndrome

Introduction: Silicone breast implants (SBI) have been used since 1962 in the reconstruction of post-mastectomy cases, in augmentation of the breast, or for cosmetic purposes, while fillers with biopolymer (FB) have been used since the 1990s. Today, they are considered adjuvants of the immune system. Most complications of SBI and FB are local in nature, but some patients experience systemic symptoms, which are defined as adjuvant-induced autoimmune inflammatory syndrome (ASIA). Aim: The aim of this study is to demonstrate the possible association of silicone breast implants and FB with the development of immune-mediated inflammatory rheumatic diseases (IMIRD). Material and methods: The research represents retrospective study which involved 15 female patients with immune-mediated inflammatory rheumatic diseases, 6 of whom were patients with implanted silicone breast implants for cosmetic reasons, and 9 patients with placement of fillers with biopolymer on the lips. Results: The average time from silicone implantation to the onset of the first symptoms was 6.10 ± 5.3 (range 6 months to 24 years). The following immune-mediated inflammatory rheumatic diseases were recorded: 3 patients with systemic sclerosis (SSc), 3 patients with undifferentiated arthritis, 3 patients with seropositive rheumatoid arthritis, 1 patient with systemic lupus erythematosus, 2 patients with undifferentiated SCTD, 2 patients with mixed connective tissue disease, and one patient with unexplained systemic disease. Seven patients had the Raynaud phenomenon. Spontaneous abortions were reported in 2 patients. Conclusion: Earlier reports that silicone breast implants and biopolymer fillers are safe, today are changing with the description of ASIA syndrome.

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