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Neurotherapeutics : the Journal of the... Oct 2021In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune... (Review)
Review
In the last 25 years, intravenous immunoglobulin (IVIg) has had a major impact in the successful treatment of previously untreatable or poorly controlled autoimmune neurological disorders. Derived from thousands of healthy donors, IVIg contains IgG1 isotypes of idiotypic antibodies that have the potential to bind pathogenic autoantibodies or cross-react with various antigenic peptides, including proteins conserved among the "common cold"-pre-pandemic coronaviruses; as a result, after IVIg infusions, some of the patients' sera may transiently become positive for various neuronal antibodies, even for anti-SARS-CoV-2, necessitating caution in separating antibodies derived from the infused IVIg or acquired humoral immunity. IVIg exerts multiple effects on the immunoregulatory network by variably affecting autoantibodies, complement activation, FcRn saturation, FcγRIIb receptors, cytokines, and inflammatory mediators. Based on randomized controlled trials, IVIg is approved for the treatment of GBS, CIDP, MMN and dermatomyositis; has been effective in, myasthenia gravis exacerbations, and stiff-person syndrome; and exhibits convincing efficacy in autoimmune epilepsy, neuromyelitis, and autoimmune encephalitis. Recent evidence suggests that polymorphisms in the genes encoding FcRn and FcγRIIB may influence the catabolism of infused IgG or its anti-inflammatory effects, impacting on individualized dosing or efficacy. For chronic maintenance therapy, IVIg and subcutaneous IgG are effective in controlled studies only in CIDP and MMN preventing relapses and axonal loss up to 48 weeks; in practice, however, IVIg is continuously used for years in all the aforementioned neurological conditions, like is a "forever necessary therapy" for maintaining stability, generating challenges on when and how to stop it. Because about 35-40% of patients on chronic therapy do not exhibit objective neurological signs of worsening after stopping IVIg but express subjective symptoms of fatigue, pains, spasms, or a feeling of generalized weakness, a conditioning effect combined with fear that discontinuing chronic therapy may destabilize a multi-year stability status is likely. The dilemmas of continuing chronic therapy, the importance of adjusting dosing and scheduling or periodically stopping IVIg to objectively assess necessity, and concerns in accurately interpreting IVIg-dependency are discussed. Finally, the merit of subcutaneous IgG, the ineffectiveness of IVIg in IgG4-neurological autoimmunities, and genetic factors affecting IVIg dosing and efficacy are addressed.
Topics: Autoantibodies; Autoimmune Diseases of the Nervous System; Autoimmunity; COVID-19; Dose-Response Relationship, Immunologic; Humans; Immunoglobulins, Intravenous; SARS-CoV-2; Treatment Outcome; Withholding Treatment
PubMed: 34766257
DOI: 10.1007/s13311-021-01108-4 -
The Journal of Investigative Dermatology Mar 2022Sex bias in immune function has been well-described, and women have been shown to counter immunologically stimulating phenomena such as infection, malignancy, and trauma... (Review)
Review
Sex bias in immune function has been well-described, and women have been shown to counter immunologically stimulating phenomena such as infection, malignancy, and trauma with more protective responses than men. Heightened immunity in women may also result in a predisposition for loss of self-tolerance and development of autoimmunity, reflected by the overwhelming female sex bias of patients with autoimmune diseases. In this review, we discuss the postulated evolutionary etiologies for sexual dimorphism in immunity. We also review the molecular mechanisms underlying divergent immune responses in men and women, including sex hormone effects, X chromosome dosage, and autosomal sex-biased genes. With increasing evidence that autoimmune disease susceptibility is influenced by numerous hormonal and genetic factors, a comprehensive understanding of these topics may facilitate the development of much-needed targeted therapeutics.
Topics: Autoimmune Diseases; Autoimmunity; Female; Humans; Male; Sex Characteristics; Sex Factors; Sexism
PubMed: 34362556
DOI: 10.1016/j.jid.2021.06.008 -
BMC Immunology Oct 2023Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic...
Digestive autoimmune conditions are a growing challenge to global health. Risk factors associated with autoimmune digestive diseases are complex, including genetic variation, immunological dysfunction, and various environmental factors. To improve our understanding of the mechanisms behind digestive autoimmune conditions, including factors causing gastrointestinal manifestations and pathogenesis, BMC Immunology has launched a new Collection "The digestive system and autoimmunity".
Topics: Humans; Autoimmunity; Autoimmune Diseases; Digestive System
PubMed: 37794375
DOI: 10.1186/s12865-023-00561-4 -
Journal of Autoimmunity May 2023Infections are known to trigger flares of autoimmune diseases in humans and serve as an inciting cause of autoimmunity in animals. Evidence suggests a causative role of... (Review)
Review
Infections are known to trigger flares of autoimmune diseases in humans and serve as an inciting cause of autoimmunity in animals. Evidence suggests a causative role of infections in triggering antigen-specific autoimmunity, previous thought mainly through antigen mimicry. However, an infection can induce bystander autoreactive T and B cell polyclonal activation, believed to result in non-pathogenic and pathogenic autoimmune responses. Lastly, epitope spreading in autoimmunity is a mechanism of epitope changes of autoreactive cells induced by infection, promoting the targeting of additional self-epitopes. This review highlights recent research findings, emphasizes infection-mediated autoimmune responses, and discusses the possible mechanisms involved.
Topics: Humans; Animals; Autoimmunity; Autoantibodies; Autoimmune Diseases; Epitopes; Communicable Diseases
PubMed: 36470769
DOI: 10.1016/j.jaut.2022.102962 -
Nature Reviews. Immunology Feb 2023Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune...
Self-reactive immune responses occur in autoimmune diseases and also in chronic inflammatory and metabolic diseases that are not generally considered as autoimmune diseases. How do the mechanisms of autoreactivity in the different settings overlap and how are they distinguished? Evidence indicates that while autoimmune diseases rely on both a supportive genetic background and a cooperative environment, chronic inflammatory and metabolic diseases strongly hinge on a conducive milieu for the activation of pathogenic autoreactive cells even in the absence of facilitating polygenic factors.
Topics: Humans; Autoimmunity; Autoantibodies
PubMed: 36418434
DOI: 10.1038/s41577-022-00812-2 -
Current Opinion in Structural Biology Aug 2022Bacteria are microscopic, single-celled organisms known for their ability to adapt to their environment. In response to stressful environmental conditions or in the... (Review)
Review
Bacteria are microscopic, single-celled organisms known for their ability to adapt to their environment. In response to stressful environmental conditions or in the presence of a contact surface, they commonly form multicellular aggregates called biofilms. Biofilms form on various abiotic or biotic surfaces through a dynamic stepwise process involving adhesion, growth, and extracellular matrix production. Biofilms develop on tissues as well as on implanted devices during infections, providing the bacteria with a mechanism for survival under harsh conditions including targeting by the immune system and antimicrobial therapy. Like pathogenic bacteria, members of the human microbiota can form biofilms. Biofilms formed by enteric bacteria contribute to several human diseases including autoimmune diseases and cancer. However, until recently the interactions of immune cells with biofilms had been mostly uncharacterized. Here, we will discuss how components of the enteric biofilm produced in vivo, specifically amyloid curli and extracellular DNA, could be interacting with the host's immune system causing an unpredicted immune response.
Topics: Amyloid; Amyloidogenic Proteins; Autoimmune Diseases; Autoimmunity; Bacteria; Biofilms; Humans
PubMed: 35863164
DOI: 10.1016/j.sbi.2022.102435 -
Frontiers in Immunology 2021
Topics: Animals; Autoimmunity; Bacteria; Humans; Viruses
PubMed: 34567014
DOI: 10.3389/fimmu.2021.752980 -
Autoimmunity Reviews May 2021The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover,... (Review)
Review
The glycosylation of the fragment crystallizable (Fc) region of immunoglobulins (Ig) is critical for the modulation of antibody effects on inflammation. Moreover, antibody glycosylation may induce pathologic modifications and ultimately contribute to the development of autoimmune diseases. Thanks to progress in the analysis of glycosylation, more data are available on IgG and its subclass structures in the context of autoimmune diseases. In this review, we focused on the impact of Ig glycosylation in autoimmunity, describing how it modulates the immune response and how glycome profiles can be used as biomarkers of disease activity. The analysis of antibody glycosylation demonstrated specific features in human autoimmune and chronic inflammatory conditions, including rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and autoimmune liver diseases, among others. Within the same disease, different patterns are associated with disease severity and treatment options. Future research may increase the information available on the distinct glycome profiles and expand their potential role as biomarkers and as targets for treatment, ultimately favoring an individualized approach.
Topics: Arthritis, Rheumatoid; Autoimmune Diseases; Autoimmunity; Glycosylation; Humans; Lupus Erythematosus, Systemic
PubMed: 33727152
DOI: 10.1016/j.autrev.2021.102804 -
International Journal of Molecular... Sep 2023Systemic sclerosis, commonly known as scleroderma, is an autoimmune disorder characterized by vascular abnormalities, autoimmunity, and multiorgan fibrosis. The exact... (Review)
Review
Systemic sclerosis, commonly known as scleroderma, is an autoimmune disorder characterized by vascular abnormalities, autoimmunity, and multiorgan fibrosis. The exact etiology is not known but believed to be triggered by environmental agents in a genetically susceptible host. Vascular symptoms such as the Raynaud phenomenon often precede other fibrotic manifestations such as skin thickening indicating that vascular dysfunction is the primary event. Endothelial damage and activation occur early, possibly triggered by various infectious agents and autoantibodies. Endothelial dysfunction, along with defects in endothelial progenitor cells, leads to defective angiogenesis and vasculogenesis. Endothelial to mesenchymal cell transformation is another seminal event during pathogenesis that progresses to tissue fibrosis. The goal of the review is to discuss the molecular aspect of the endothelial dysfunction that leads to the development of systemic sclerosis.
Topics: Humans; Vascular Diseases; Scleroderma, Systemic; Autoantibodies; Autoimmunity; Fibrosis
PubMed: 37762689
DOI: 10.3390/ijms241814385 -
Cells Mar 2022Lymphatic vessels provide a critical line of communication between peripheral tissues and their draining lymph nodes, which is necessary for robust immune responses... (Review)
Review
Lymphatic vessels provide a critical line of communication between peripheral tissues and their draining lymph nodes, which is necessary for robust immune responses against infectious agents. At the same time, lymphatics help shape the nature and kinetics of immune responses to ensure resolution, limit tissue damage, and prevent autoimmune responses. A variety of pathogens have developed strategies to exploit these functions, from multicellular organisms like nematodes to bacteria, viruses, and prions. While lymphatic vessels serve as transport routes for the dissemination of many pathogens, their hypoxic and immune-suppressive environments can provide survival niches for others. Lymphatics can be exploited as perineural niches, for inter-organ distribution among highly motile carrier cells, as effective replicative niches, and as alternative routes in response to therapy. Recent studies have broadened our understanding of lymphatic involvement in pathogenic spread to include a wider range of pathogens, as well as new mechanisms of exploitation, which we summarize here.
Topics: Autoimmunity; Immunity; Lymph Nodes; Lymphatic System; Lymphatic Vessels
PubMed: 35326430
DOI: 10.3390/cells11060979