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1.
Curr Opin Immunol ; 72: 230-238, 2021 10.
Article in English | MEDLINE | ID: covidwho-1603901

ABSTRACT

The study of monogenic autoimmune diseases has provided key insights into molecular mechanisms involved in development of autoimmunity and immune tolerance. It has also become clear that such inborn errors of immunity (IEIs) frequently present clinically not only with autoimmune diseases, but also frequently have increased susceptibility to infection. The genes associated with monogenic autoimmunity influence diverse functional pathways, and the resulting immune dysregulation also impacts the complex and coordinated immune response to pathogens, for example type I interferon and cytokine signaling, the complement pathway and proper differentiation of the immune response. The SARS-CoV-2 pandemic has highlighted how monogenic autoimmunity can increase risk for serious infection with the discovery of severe disease in patients with pre-existing antibodies to Type I IFNs. This review discusses recent insight into the relationship between monogenic autoimmunity and infectious diseases.


Subject(s)
Autoimmune Diseases/immunology , COVID-19/immunology , Communicable Diseases/immunology , SARS-CoV-2/physiology , Animals , Autoimmune Diseases/genetics , COVID-19/genetics , Communicable Diseases/genetics , Disease Susceptibility , Humans , Interferon Type I/metabolism
2.
Cells ; 10(12)2021 12 20.
Article in English | MEDLINE | ID: covidwho-1580997

ABSTRACT

There is growing evidence that coronavirus disease 2019 (COVID-19) can lead to a dysregulation of the immune system with the development of autoimmune phenomena. The consequence of this immune dysregulation ranges from the production of autoantibodies to the onset of rheumatic autoimmune disease. In this context, we conducted a systematic review to analyze the current data regarding the new-onset systemic and rheumatic autoimmune diseases in COVID-19 patients. A literature search in PubMed and Scopus databases from December 2019 to September 2021 identified 99 patients that fulfilled the specific diagnostic/classification criteria and/or nomenclature for each rheumatic autoimmune disease. The main diseases reported were vasculitis and arthritis. Idiopathic inflammatory myopathies, systemic lupus erythematosus, and sarcoidosis were also reported in a limited number of patients, as well as isolated cases of systemic sclerosis and adult-onset Still's disease. These findings highlight the potential spectrum of systemic and rheumatic autoimmune diseases that could be precipitated by SARS-CoV-2 infection. Complementary studies are needed to discern the link between the SARS-CoV-2 and new onset-rheumatic diseases so that this knowledge can be used in early diagnosis and the most suitable management.


Subject(s)
Autoimmune Diseases , COVID-19 Testing , COVID-19 , SARS-CoV-2/immunology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19/immunology , Humans
3.
Reumatol Clin (Engl Ed) ; 17(9): 491-493, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1510266

ABSTRACT

SARS-COV-2 infection has spread worldwide since it originated in December 2019, in Wuhan, China. The pandemic has largely demonstrated the resilience of the world's health systems and is the greatest health emergency since World War II. There is no single therapeutic approach to the treatment of COVID-19 and the associated immune disorder. The lack of randomised clinical trials (RCTs) has led different countries to tackle the disease based on case series, or from results of observational studies with off-label drugs. We as rheumatologists in general, and specifically rheumatology fellows, have been on the front line of the pandemic, modifying our activities and altering our training itinerary. We have attended patients, we have learned about the management of the disease and from our previous experience with drugs for arthritis and giant cell arteritis, we have used these drugs to treat COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Biological Factors/therapeutic use , COVID-19/drug therapy , Immunosuppressive Agents/therapeutic use , Physician's Role , Rheumatologists , Autoimmune Diseases/complications , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19/epidemiology , COVID-19/immunology , Drug Therapy, Combination , Education, Medical, Graduate , Fellowships and Scholarships , Global Health , Humans , Immunocompromised Host , Opportunistic Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/immunology , Patient Care Team/organization & administration , Practice Patterns, Physicians' , Rheumatic Diseases/complications , Rheumatic Diseases/drug therapy , Rheumatic Diseases/immunology , Rheumatologists/education , Rheumatologists/organization & administration , Rheumatology/education , Rheumatology/methods , Rheumatology/organization & administration , Spain/epidemiology
4.
Scand J Immunol ; 94(5): e13101, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1501497

ABSTRACT

The coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenged globally with its morbidity and mortality. A small percentage of affected patients (20%) progress into the second stage of the disease clinically presenting with severe or fatal involvement of lung, heart and vascular system, all contributing to multiple-organ failure. The so-called 'cytokines storm' is considered the pathogenic basis of severe disease and it is a target for treatment with corticosteroids, immunotherapies and intravenous immunoglobulin (IVIg). We provide an overview of the role of IVIg in the therapy of adult patients with COVID-19 disease. After discussing the possible underlying mechanisms of IVIg immunomodulation in COVID-19 disease, we review the studies in which IVIg was employed. Considering the latest evidence that show a link between new coronavirus and autoimmunity, we also discuss the use of IVIg in COVID-19 and anti-SARS-CoV-2 vaccination related autoimmune diseases and the post-COVID-19 syndrome. The benefit of high-dose IVIg is evident in almost all studies with a rapid response, a reduction in mortality and improved pulmonary function in critically ill COVID-19 patients. It seems that an early administration of IVIg is crucial for a successful outcome. Studies' limitations are represented by the small number of patients, the lack of control groups in some and the heterogeneity of included patients. IVIg treatment can reduce the stay in ICU and the demand for mechanical ventilation, thus contributing to attenuate the burden of the disease.


Subject(s)
Antiviral Agents/therapeutic use , Autoimmune Diseases/prevention & control , COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/drug therapy , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/physiology , Adult , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , COVID-19/etiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Chemotherapy, Adjuvant , Critical Illness , Humans , Italy , Length of Stay , Respiration, Artificial , Treatment Outcome
5.
Immunology ; 164(4): 722-736, 2021 12.
Article in English | MEDLINE | ID: covidwho-1494730

ABSTRACT

Bruton's tyrosine kinase (BTK) is a TEC kinase with a multifaceted role in B-cell biology and function, highlighted by its position as a critical component of the B-cell receptor signalling pathway. Due to its role as a therapeutic target in several haematological malignancies including chronic lymphocytic leukaemia, BTK has been gaining tremendous momentum in recent years. Within the immune system, BTK plays a part in numerous pathways and cells beyond B cells (i.e. T cells, macrophages). Not surprisingly, BTK has been elucidated to be a driving factor not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. To extort this role, BTK inhibitors such as ibrutinib have been developed to target BTK in other diseases. However, due to rising levels of resistance, the urgency to develop new inhibitors with alternative modes of targeting BTK is high. To meet this demand, an expanding list of BTK inhibitors is currently being trialled. In this review, we synopsize recent discoveries regarding BTK and its role within different immune cells and pathways. Additionally, we discuss the broad significance and relevance of BTK for various diseases ranging from haematology and rheumatology to the COVID-19 pandemic. Overall, BTK signalling and its targetable nature have emerged as immensely important for a wide range of clinical applications. The development of novel, more specific and less toxic BTK inhibitors could be revolutionary for a significant number of diseases with yet unmet treatment needs.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/metabolism , B-Lymphocytes/enzymology , Immune System/enzymology , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Animals , Autoimmune Diseases/drug therapy , Autoimmune Diseases/enzymology , Autoimmune Diseases/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/immunology , Humans , Immune System/drug effects , Immune System/immunology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/enzymology , Lymphoproliferative Disorders/immunology , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Receptors, Antigen, B-Cell/metabolism , Receptors, Chemokine/metabolism , Signal Transduction , Toll-Like Receptors/metabolism
6.
Signal Transduct Target Ther ; 6(1): 367, 2021 10 20.
Article in English | MEDLINE | ID: covidwho-1475287

ABSTRACT

Cytokine release syndrome (CRS) embodies a mixture of clinical manifestations, including elevated circulating cytokine levels, acute systemic inflammatory symptoms and secondary organ dysfunction, which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza, SARS-CoV and COVID-19, immunotherapy of tumor, after chimeric antigen receptor T (CAR-T) therapy, and in monogenic disorders and autoimmune diseases. Particularly, severe CRS is a very significant and life-threatening complication, which is clinically characterized by persistent high fever, hyperinflammation, and severe organ dysfunction. However, CRS is a double-edged sword, which may be both helpful in controlling tumors/viruses/infections and harmful to the host. Although a high incidence and high levels of cytokines are features of CRS, the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain unclear. In the present review, we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of CRS. Considering that CRS is the major adverse event in human diseases and intervention therapy, our review delineates the characteristics, kinetics, signaling pathways, and potential mechanisms of CRS, which shows its clinical relevance for achieving both favorable efficacy and low toxicity.


Subject(s)
Cytokine Release Syndrome , Signal Transduction/immunology , Acute Disease , Autoimmune Diseases/complications , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/therapy , Graft vs Host Disease/complications , Graft vs Host Disease/immunology , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , Humans , Immunotherapy, Adoptive/adverse effects , Influenza, Human/complications , Influenza, Human/immunology , Neoplasms/complications , Neoplasms/immunology , Neoplasms/therapy , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/complications , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/therapy
7.
Int J Mol Sci ; 22(20)2021 Oct 18.
Article in English | MEDLINE | ID: covidwho-1470895

ABSTRACT

Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.


Subject(s)
Adaptive Immunity , Autoimmune Diseases/pathology , Cytokine Release Syndrome/pathology , Immunity, Innate , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Cytokines/metabolism , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , SARS-CoV-2/isolation & purification
8.
Immunology ; 164(4): 722-736, 2021 12.
Article in English | MEDLINE | ID: covidwho-1429802

ABSTRACT

Bruton's tyrosine kinase (BTK) is a TEC kinase with a multifaceted role in B-cell biology and function, highlighted by its position as a critical component of the B-cell receptor signalling pathway. Due to its role as a therapeutic target in several haematological malignancies including chronic lymphocytic leukaemia, BTK has been gaining tremendous momentum in recent years. Within the immune system, BTK plays a part in numerous pathways and cells beyond B cells (i.e. T cells, macrophages). Not surprisingly, BTK has been elucidated to be a driving factor not only in lymphoproliferative disorders but also in autoimmune diseases and response to infection. To extort this role, BTK inhibitors such as ibrutinib have been developed to target BTK in other diseases. However, due to rising levels of resistance, the urgency to develop new inhibitors with alternative modes of targeting BTK is high. To meet this demand, an expanding list of BTK inhibitors is currently being trialled. In this review, we synopsize recent discoveries regarding BTK and its role within different immune cells and pathways. Additionally, we discuss the broad significance and relevance of BTK for various diseases ranging from haematology and rheumatology to the COVID-19 pandemic. Overall, BTK signalling and its targetable nature have emerged as immensely important for a wide range of clinical applications. The development of novel, more specific and less toxic BTK inhibitors could be revolutionary for a significant number of diseases with yet unmet treatment needs.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/metabolism , B-Lymphocytes/enzymology , Immune System/enzymology , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Animals , Autoimmune Diseases/drug therapy , Autoimmune Diseases/enzymology , Autoimmune Diseases/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/immunology , Humans , Immune System/drug effects , Immune System/immunology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/enzymology , Lymphoproliferative Disorders/immunology , Molecular Targeted Therapy , Protein Kinase Inhibitors/therapeutic use , Receptors, Antigen, B-Cell/metabolism , Receptors, Chemokine/metabolism , Signal Transduction , Toll-Like Receptors/metabolism
9.
Front Immunol ; 12: 722979, 2021.
Article in English | MEDLINE | ID: covidwho-1399139

ABSTRACT

The immunopathology of type I diabetes (T1D) presents a complicated case in part because of the multifactorial origin of this disease. Typically, T1D is thought to occur as a result of autoimmunity toward islets of Langerhans, resulting in the destruction of insulin-producing cells (ß cells) and thus lifelong reliance on exogenous insulin. However, that explanation obscures much of the underlying mechanism, and the actual precipitating events along with the associated actors (latent viral infection, diverse immune cell types and their roles) are not completely understood. Notably, there is a malfunctioning in the regulation of cytotoxic CD8+ T cells that target endocrine cells through antigen-mediated attack. Further examination has revealed the likelihood of an imbalance in distinct subpopulations of tolerogenic and cytotoxic natural killer (NK) cells that may be the catalyst of adaptive immune system malfunction. The contributions of components outside the immune system, including environmental factors such as chronic viral infection also need more consideration, and much of the recent literature investigating the origins of this disease have focused on these factors. In this review, the details of the immunopathology of T1D regarding NK cell disfunction is discussed, along with how those mechanisms stand within the context of general autoimmune disorders. Finally, the rarer cases of latent autoimmune, COVID-19 (viral), and immune checkpoint inhibitor (ICI) induced diabetes are discussed as their exceptional pathology offers insight into the evolution of the disease as a whole.


Subject(s)
Autoimmune Diseases/immunology , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Autoantibodies/immunology , Autoimmune Diseases/pathology , COVID-19/complications , Diabetes Mellitus, Type 1/etiology , Humans , Insulin/metabolism , Insulin-Secreting Cells/immunology , Virus Diseases/complications
10.
Ann Rheum Dis ; 80(10): 1345-1350, 2021 10.
Article in English | MEDLINE | ID: covidwho-1394067

ABSTRACT

OBJECTIVES: Evidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation. METHODS: Patients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls. RESULTS: All healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p<0.001). Patients without detectable CD19+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, p<0.001). However, even patients with a low number of B cells (<1%) mounted detectable SARS-CoV-2-specific antibody responses. SARS-CoV-2-specific T cells were detected in 58% of the patients, independent of a humoral immune response. CONCLUSIONS: The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Rituximab/therapeutic use , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , B-Lymphocytes/immunology , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunogenicity, Vaccine/drug effects , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology
11.
Int J Mol Sci ; 22(2)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1389386

ABSTRACT

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient's immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.


Subject(s)
Autoimmune Diseases/immunology , Extracellular Traps/immunology , Neutrophils/immunology , Aortic Aneurysm, Abdominal/pathology , Autoimmune Diseases/pathology , Autoimmunity/immunology , COVID-19/immunology , COVID-19/pathology , Humans , Neutrophil Activation/immunology , Plaque, Atherosclerotic/pathology , Thrombosis/pathology
13.
Front Immunol ; 11: 631743, 2020.
Article in English | MEDLINE | ID: covidwho-1389175

ABSTRACT

The concept of trained immunity has recently emerged as a mechanism contributing to several immune mediated inflammatory conditions. Trained immunity is defined by the immunological memory developed in innate immune cells after a primary non-specific stimulus that, in turn, promotes a heightened inflammatory response upon a secondary challenge. The most characteristic changes associated to this process involve the rewiring of cell metabolism and epigenetic reprogramming. Under physiological conditions, the role of trained immune cells ensures a prompt response. This action is limited by effective resolution of inflammation and tissue repair in order to restore homeostasis. However, unrestrained activation of innate immune cells contributes to the development of chronic inflammation and tissue destruction through the secretion of inflammatory cytokines, proteases and growth factors. Therefore, interventions aimed at reversing the changes induced by trained immunity provide potential therapeutic approaches to treat inflammatory and autoimmune diseases like rheumatoid arthritis (RA). We review cellular approaches that target metabolism and the epigenetic reprogramming of dendritic cells, macrophages, natural killer cells, and other trained cells in the context of autoimmune inflammatory diseases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmunity/drug effects , Biological Products/therapeutic use , Immune System/drug effects , Inflammation/drug therapy , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , COVID-19/drug therapy , COVID-19/immunology , Energy Metabolism/drug effects , Epigenesis, Genetic/drug effects , Humans , Immune System/immunology , Immune System/metabolism , Immunity, Innate/drug effects , Immunologic Memory/drug effects , Inflammation/genetics , Inflammation/immunology , Inflammation/metabolism , Signal Transduction
14.
Front Immunol ; 12: 705772, 2021.
Article in English | MEDLINE | ID: covidwho-1376700

ABSTRACT

Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.


Subject(s)
Autoimmunity , COVID-19 Vaccines/immunology , COVID-19/immunology , Proteome/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Autoimmune Diseases/etiology , Autoimmune Diseases/immunology , COVID-19/complications , COVID-19 Vaccines/adverse effects , Computer Simulation , Epitopes, B-Lymphocyte/immunology , HLA Antigens/immunology , Humans , Peptide Fragments/immunology , Peptide Library
15.
J Med Virol ; 94(1): 54-62, 2022 01.
Article in English | MEDLINE | ID: covidwho-1370368

ABSTRACT

Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.


Subject(s)
Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , Autoimmunity/immunology , COVID-19/pathology , SARS-CoV-2/immunology , Autoantibodies/blood , Autoantibodies/immunology , Autoimmune Diseases/virology , COVID-19/immunology , Humans
16.
Immunol Res ; 69(6): 576-583, 2021 12.
Article in English | MEDLINE | ID: covidwho-1366407

ABSTRACT

The development of vaccines to prevent SARS-CoV-2 infection has mainly relied on the induction of neutralizing antibodies (nAbs) to the Spike protein of SARS-CoV-2, but there is growing evidence that T cell immune response can contribute to protection as well. In this study, an anti-receptor binding domain (RBD) antibody assay and an INFγ-release assay (IGRA) were used to detect humoral and cellular responses to the Pfizer-BioNTech BNT162b2 vaccine in three separate cohorts of COVID-19-naïve patients: 108 healthcare workers (HCWs), 15 elderly people, and 5 autoimmune patients treated with immunosuppressive agents. After the second dose of vaccine, the mean values of anti-RBD antibodies (Abs) and INFγ were 123.33 U/mL (range 27.55-464) and 1513 mIU/mL (range 145-2500) in HCWs and 210.7 U/mL (range 3-500) and 1167 mIU/mL (range 83-2500) in elderly people. No correlations between age and immune status were observed. On the contrary, a weak but significant positive correlation was found between INFγ and anti-RBD Abs values (rho = 0.354, p = 0.003). As to the autoimmune cohort, anti-RBD Abs were not detected in the two patients with absent peripheral CD19+B cells, despite high INFγ levels being observed in all 5 patients after vaccination. Even though the clinical relevance of T cell response has not yet been established as a correlate of vaccine-induced protection, IGRA testing has showed optimal sensitivity and specificity to define vaccine responders, even in patients lacking a cognate antibody response to the vaccine.


Subject(s)
COVID-19 Vaccines/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunocompromised Host/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Autoimmune Diseases/immunology , B-Lymphocytes/immunology , COVID-19/immunology , COVID-19/prevention & control , Female , Health Personnel/statistics & numerical data , Humans , Immunogenicity, Vaccine/immunology , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Interferon-gamma/blood , Lymphocyte Count , Male , Middle Aged , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Vaccination , Young Adult
17.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1367847

ABSTRACT

While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body's adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.


Subject(s)
Autoimmune Diseases/immunology , Autoimmune Diseases/virology , COVID-19/immunology , Adaptive Immunity , Arthritis, Rheumatoid/immunology , Autoantibodies/immunology , Autoantigens/immunology , Autoimmunity , COVID-19/virology , Humans , Lupus Erythematosus, Systemic/immunology , SARS-CoV-2/immunology
18.
Front Immunol ; 12: 624703, 2021.
Article in English | MEDLINE | ID: covidwho-1354863

ABSTRACT

Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.


Subject(s)
Autoimmune Diseases/metabolism , Autoimmunity , Cardiomyopathies/metabolism , Inflammation Mediators/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Tenascin/metabolism , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Cardiomyopathies/immunology , Cardiomyopathies/pathology , Cellular Microenvironment , Humans , Myocarditis/immunology , Myocarditis/pathology , Myocardium/immunology , Myocardium/pathology , Self Tolerance , Signal Transduction
20.
Ann Rheum Dis ; 80(10): 1322-1329, 2021 10.
Article in English | MEDLINE | ID: covidwho-1346035

ABSTRACT

OBJECTIVE: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination. METHODS: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases. RESULTS: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy. CONCLUSION: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.


Subject(s)
Autoimmune Diseases/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Autoimmune Diseases/drug therapy , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunosuppressive Agents/immunology , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , SARS-CoV-2 , T-Lymphocytes/immunology
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