Lymphopenia is strongly associated with autoimmune diseases. The molecular mechanisms that link both phenomena are still unclear, but certain key pathways have been described. Central tolerance is as important as peripheral. In the earlier, epithelial and dendritic cells play a crucial role in the selection of clones. In the latter, regulatory T cells (Tregs) rise as inductors of anergy in order to prevent the development of autoimmune pathology. In lymphopenic conditions, T cells develop the process of lymphopenia-induced proliferation (LIP). A complex interaction between the major histocompatibility complex (MHC) and the T cell receptor (TCR) makes this process possible. Furthermore, IL-7 can act synergistically or in an independent manner to promote LIP. A lack of Transforming Growth Factor-β (TGF-β) was recently described as the second hit needed to develop autoimmunity in a lymphopenic microenvironment, given its actions in Tregs and its interaction with CTLA-4. Regarding autoimmune clinical scenarios, lymphopenia is related to both, systemic and organ-specific diseases. Thus, the molecular study of such patients has been limited and needs to be widened to the pathways shown here to be involved in the development of lymphopenia and autoimmunity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.humimm.2016.06.016 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Systemic lupus erythematosus in a patient with 22q11.2 deletion syndrome: A case report and review of the literature.
Cent Eur J Immunol
November 2024
Department of Rheumatology and Immunology, Hangzhou Normal University Affiliated Hospital, Hangzhou, China.
22q11.2 deletion syndrome (MIM: 192430/188400, ORPHA: 567) is the most common chromosomal microdeletion disorder, caused by a hemizygous microdeletion of 2.5 million base pairs on chromosome 22.
View Article and Find Full Text PDFThe Severity of COVID-19 in Systemic Lupus Erythematosus Patient.
Infect Disord Drug Targets
December 2024
Department of Pharmaceutical Chemistry, Dadasaheb Balpande College of Pharmacy, Nagpur, 440037, Maharashtra, India.
As of early October 2020, the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, resulted in approximately 35 million cases and one million fatalities worldwide. Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the generation of pathogenic autoantibodies and a lack of tolerance to nuclear self-antigens. Hypocomple-mentemia, or an abnormal blood complement deficit, is a reliable predictor of infection in SLE patients.
View Article and Find Full Text PDFSevere Outcomes of Pneumocystis Pneumonia: A 10-year Retrospective Cohort Study.
Transpl Infect Dis
December 2024
Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, University of Toronto, Toronto, Canada.
Background: A considerable knowledge gap exists in predicting severe Pneumocystis pneumonia (PCP) outcomes following PCP diagnosis.
Methods: In this retrospective cohort, we studied immunocompromised patients with PCP admitted to 5 University Health Network centers in Canada (2011-2022). The study outcome included severe PCP, a composite of 21-day ICU admission or 28-day all-cause mortality.
Impact of Anti-CD4 Autoantibodies on Immune Reconstitution in People With Advanced Human Immunodeficiency Virus.
Clin Infect Dis
December 2024
Laboratory of Immunoregulation.
Background: Despite suppressive antiretroviral therapy (ART), 15%-30% of people with human immunodeficiency virus (HIV) experience a limited recovery of CD4 T cells. Although autoantibodies against the CD4 receptor have previously been identified in people with HIV (PWH), little is known about their longitudinal impact on CD4 T-cell reconstitution.
Methods: Anti-CD4 autoantibodies were evaluated by the fluid-phase luciferase immunoprecipitation systems immunoassay in ART-naive people with advanced HIV (CD4 count ≤100 cells/µL), PWH with CD4 count >200 cells/µL, long-term nonprogressors, people with idiopathic CD4 lymphopenia, people with autoimmune lymphoproliferative syndrome, and healthy volunteers without HIV.
Abatacept Induces Long-Term Reconstitution of the B-Cell Niche in a Patient With CTLA-4 Haploinsufficiency: A Case Report.
Neurol Neuroimmunol Neuroinflamm
March 2025
Department of Neurology, Medical Faculty and University Hospital Duesseldorf, Germany.
Objectives: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency is a rare genetic condition characterized by development of immune cytopenia, hypogammaglobulinemia, and/or lymphoproliferative disorder, as well as multiple autoimmunity. Treatment with abatacept was shown to alleviate autoimmune conditions, yet its long-lasting impact on bone marrow function remains undetermined.
Methods: We here present the case of a now 39-year-old woman with CTLA-4 haploinsufficiency with predominant CNS affection, yet multiorgan autoimmunity and lymphopenia.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!