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Rheumatology and Therapy

Is a Functional Cure Possible in Autoimmune Diseases? Evidence from Trigger Eradication, Transplantation, and Cellular Therapies

Authors
Jozélio Freire de Carvalho
Carlos Ewerton Maia Rodrigues
Published in
Rheumatology and Therapy

Abstract

Introduction

Traditionally considered incurable, autoimmune diseases (AIDs) may—in specific circumstances—achieve sustained remission or even a “functional cure,” defined as durable clinical and laboratory remission without immunosuppression. This review evaluates evidence across five therapeutic axes: infectious trigger eradication, immune reset via autologous hematopoietic stem cell transplantation (HSCT), cellular therapies (CAR-T, extracorporeal photopheresis), environmental/nutritional strategies, and paraneoplastic syndromes.

Methods

Systematic review according to PRISMA guidelines in PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane (up to September 2025). Eligible studies included trials, meta-analyses, cohorts, case series, and reports describing sustained or drug-free remission. Definitions applied were clinical remission, complete remission, sustained remission ≥ 12 months, drug-free remission, and functional cure (complete, off-therapy remission with stable biomarkers and no new organ damage).

Results

Strong evidence supports Helicobacter pylori eradication in immune thrombocytopenic purpura, with signals in dermatoses and urticaria. In systemic sclerosis, HSCT outperformed cyclophosphamide in randomized trials, improving survival and reducing prolonged immunosuppression; lupus series reported extended drug-free remissions. Anti-CD19 CAR-T therapies induced deep remission in B-cell-mediated AIDs, normalizing autoantibodies over 12–24 months. Photopheresis showed safety but heterogeneous efficacy. Environmental interventions (vitamin D, plant-based diet, microbiota modulation) suggested benefit, though with limited evidence for cure. In paraneoplastic syndromes, tumor control often coincided with autoimmune remission.

Conclusions

Functional cure in AIDs appears achievable in selected cases through trigger removal, immune reset, or profound immune depletion. Advancing this paradigm requires standardized definitions, predictive biomarkers, and long-term controlled trials to integrate these strategies into routine care.
Title
Is a Functional Cure Possible in Autoimmune Diseases? Evidence from Trigger Eradication, Transplantation, and Cellular Therapies
Authors
Jozélio Freire de Carvalho
Carlos Ewerton Maia Rodrigues
Publication date
23-12-2025
Publisher
Springer Healthcare
Published in
Rheumatology and Therapy
Print ISSN: 2198-6576
Electronic ISSN: 2198-6584
DOI
https://doi.org/10.1007/s40744-025-00816-z
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