ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human autoimmunity after lymphocyte depletion is caused by homeostatic T-cell proliferation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- The role of alemtuzumab in the development of secondary autoimmunity in multiple Sclerosis: a systematic review.Journal of neuroinflammation · 2024Pooled it
- Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis.Journal of neuroinflammation · 2020Trial
- Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab.Neurology(R) neuroimmunology & neuroinflammation · 2020Trial
- Immune thrombocytopenia in alemtuzumab-treated MS patients: Incidence, detection, and management.Multiple sclerosis (Houndmills, Basingstoke, England) · 2020Trial
- Trial
- Signatures of immune reprogramming in anti-CD52 therapy of MS: markers for risk stratification and treatment response.Neurological research and practice · 2019Trial
- Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab.JAMA neurology · 2017Trial
- ALAIN01--Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential.BMC neurology · 2016Trial
- Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.Neurology · 2014Trial
- Adenosine signaling promotes double-negative T-cell anticancer responses in conditions of CD8 T-cell lymphopenia.Blood immunology & cellular therapy · 2026Article
- Thyroid Storm Following Alemtuzumab-based Allogeneic Stem Cell Transplantation: A Case Report and Literature Review.Internal medicine (Tokyo, Japan) · 2026Review
- Dysregulation of homeostatic cytokine receptors drives prolonged T cell activation following acute SARS-CoV-2 infection in humans.Nature communications · 2025Article
- Case Reports of Teprotumumab as Treatment for Monoclonal Antibody-Induced Thyroid Orbitopathy.Reports (MDPI) · 2025Article
- Clinical management of alemtuzumab-induced autoimmune thyroid diseases: a narrative review.European thyroid journal · 2025Review
- Relevance of Recent Thymic Emigrants Following Allogeneic Hematopoietic Cell Transplantation for Pediatric Patients with Inborn Errors of Immunity.Transplantation and cellular therapy · 2025Article
- Evaluation of T-cell repertoire by flow cytometric analysis in primary immunodeficiencies with DNA repair defects.Scandinavian journal of immunology · 2025Article
- The role of regulatory T cells in central nervous system diseases in dogs: fighting with a double-edged sword toward translational discoveries.American journal of translational research · 2025Review
- Naturally arising memory-phenotype CD4Science advances · 2024Article
- A case of relapsing anti-GBM disease secondary to alemtuzumab therapy.CEN case reports · 2024Article
- Psoriasisform dermatitis following anti-CD20 therapies: Immunologic lessons and management dilemmas.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The association between lymphopenia and autoimmunity is recognized, but the underlying mechanisms are poorly understood and have not been studied systematically in humans. People with multiple sclerosis treated with the lymphocyte-depleting monoclonal antibody alemtuzumab offer a unique opportunity to study this phenomenon; one in three people develops clinical autoimmunity, and one in three people develops asymptomatic autoantibodies after treatment. Here, we show that T-cell recovery after alemtuzumab is driven by homeostatic proliferation, leading to the generation of chronically activated (CD28(-)CD57(+)), highly proliferative (Ki67(+)), oligoclonal, memory-like CD4 and CD8 T cells (CCR7(-)CD45RA(-) or CCR7(-)CD45RA(+)) capable of producing proinflammatory cytokines. Individuals who develop autoimmunity after treatment are no more lymphopenic than their nonautoimmune counterparts, but they show reduced thymopoiesis and generate a more restricted T-cell repertoire. Taken together, these findings demonstrate that homeostatic proliferation drives lymphopenia-associated autoimmunity in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.