Understanding the Concept of Pre-Clinical Autoimmunity: Prediction and Prevention of Systemic Lupus Erythematosus: Identifying Risk Factors and Developing Strategies Against Disease Development

Choi, May Y.; Costenbader, Karen H.

doi:10.3389/fimmu.2022.890522

Cited by 28 publications

(26 citation statements)

References 216 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The boundary between pre-clinical autoimmunity and autoimmune disease is vague and depends on the degree of patient symptomatology, availability of laboratory data and appropriate recognition by the provider. For some conditions, the term ‘incomplete’ disease is used, suggesting that, although clinical findings are present, they do not fully meet diagnostic or classification criteria for ‘complete’ disease 137 .…”

Section: Stages Of Autoimmunity Diseasementioning

confidence: 99%

Pathogenesis of autoimmune disease

Pisetsky

2023

Nat Rev Nephrol

178

View full text Add to dashboard Cite

Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur widely and affect individuals of all ages, especially women. Among these diseases, the most prominent immunological manifestation is the production of autoantibodies, which provide valuable biomarkers for diagnosis, classification and disease activity. Although T cells have a key role in pathogenesis, they are technically more difficult to assay. In general, autoimmune disease results from an interplay between a genetic predisposition and environmental factors. Genetic predisposition to autoimmunity is complex and can involve multiple genes that regulate the function of immune cell populations. Less frequently, autoimmunity can result from single-gene mutations that affect key regulatory pathways. Infection seems to be a common trigger for autoimmune disease, although the microbiota can also influence pathogenesis. As shown in seminal studies, patients may express autoantibodies many years before the appearance of clinical or laboratory signs of disease — a period called pre-clinical autoimmunity. Monitoring autoantibody expression in at-risk populations may therefore enable early detection and the initiation of therapy to prevent or attenuate tissue damage. Autoimmunity may not be static, however, and remission can be achieved by some patients treated with current agents.

show abstract

Section: Stages Of Autoimmunity Diseasementioning

confidence: 99%

Pathogenesis of autoimmune disease

Pisetsky

2023

Nat Rev Nephrol

178

View full text Add to dashboard Cite

show abstract

“…The development and progression of SLE involves a complex interaction of genetic risk, diet, environmental influences, and immune dysregulation ( 3 , 25 ). Individuals with genetic risk alleles for SLE who are exposed to environmental risk factors during their lifetime could be more susceptible to autoimmune diseases where synergistic interactions facilitate the onset of pathogenic autoimmune responses.…”

Section: Genetic Basis Of Aberrant T Cell Activation In Human and Mur...mentioning

confidence: 99%

Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus

et al. 2022

View full text Add to dashboard Cite

In the normal immune system, T cell activation is tightly regulated and controlled at several levels to ensure that activation occurs in the right context to prevent the development of pathologic conditions such as autoimmunity or other harmful immune responses. CD4+FoxP3+ regulatory T cells (Treg) are crucial for the regulation of T cell responses in the peripheral lymphatic organs and thus for the prevention and control of autoimmunity. In systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease with complex etiology, a disbalance between Treg and pathogenic effector/memory CD4+ T cells develops during disease progression indicating that gradual loss of control over T cell activation is an important event in the immune pathogenesis. This progressive failure to adequately regulate the activation of autoreactive T cells facilitates chronic activation and effector/memory differentiation of pathogenic T cells, which are considered to contribute significantly to the induction and perpetuation of autoimmune processes and tissue inflammation in SLE. However, in particular in humans, little is known about the factors which drive the escape from immune regulation and the chronicity of pathogenic T cell responses in an early stage of autoimmune disease when clinical symptoms are still unapparent. Here we briefly summarize important findings and discuss current views and models on the mechanisms related to the dysregulation of T cell responses which promotes chronicity and pathogenic memory differentiation with a focus on the early stage of disease in lupus-prone individuals.

show abstract

“…In SLE, rheumatoid arthritis and type 1 diabetes (T1DM) the presence of disease-specific autoantibodies prior to clinical disease manifestation is well-established (6)(7)(8)(9)(10). This is less well characterized for autoantibodies targeting BP180 or BP230, which characterize and cause bullous pemphigoid (14).…”

Section: From Health To Autoimmunitymentioning

confidence: 99%

Editorial: Autoimmune pre-disease

et al. 2023

View full text Add to dashboard Cite

According to the revised Witebsky postulates, diseases are of an autoimmune nature if, (i) the clinical phenotype can be reproduced through the transfer of autoantibodies and/or lymphocytes; (ii) the disease can be reproduced in experimental animal models; (iii) autoreactive T cells or autoantibodies are identified; and/or (iv) distinctive clinical observations, such as an HLA association, are found (1). These postulates mostly still hold true despite they were made 3 decades ago. However, in psoriasis, lichen sclerosus and lichen planus, which are considered chronic, non-communicable inflammatory diseases, autoreactive T cells and/or autoantibodies that potentially contribute to disease pathogenesis are also detected (2-5). Thus, rather than a clear distinction between autoimmune and chronic non-communicable inflammatory diseases, categorization of a given distinct disease may be better placed in the continuum between the two. Hence, within this research topic, we cover both "classic" autoimmune diseases, such as systemic lupus erythematosus (SLE), as well as non-communicable, inflammatory diseases with detectable autoimmunity, e.g., psoriasis.Autoimmune diseases develop over a long time, which at least spans over several years. This is maybe best demonstrated by the presence of disease-specific autoantibodies years prior to diagnosis of the corresponding autoimmune disease (6-10). The presence of disease-specific autoantibodies, does not, however, reliably predict if clinical manifestation of the corresponding autoimmune disease will occur in the future. Therefore, definite biomarkers that define the transition (i) from health to autoimmunity, (ii) from autoimmunity to autoimmune disease, and (iii) to chronicity or resolution of inflammation (Figure 1) would allow to implement measures to slow or prevent disease progression. This would have a significant impact on affected individuals, as well as the healthcare system because the incidence of autoimmune and non-communicable inflammatory diseases is rising and there are still many unmet medical needs in the care of patients with these diagnoses (12, 13).

show abstract

Understanding the Concept of Pre-Clinical Autoimmunity: Prediction and Prevention of Systemic Lupus Erythematosus: Identifying Risk Factors and Developing Strategies Against Disease Development

Cited by 28 publications

References 216 publications

Pathogenesis of autoimmune disease

Pathogenesis of autoimmune disease

Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus

Editorial: Autoimmune pre-disease

Contact Info

Product

Resources

About