The landscape of Chimeric Antigen Receptor (CAR) T-cell therapy is expanding into autoimmune diseases, bringing to light a novel clinical entity known as Local Immune Effector Cell-Associated Toxicity Syndrome (LICATS). Unlike the systemic inflammatory reaction of Cytokine Release Syndrome (CRS), which typically presents acutely within 48 hours and features elevated IL-6 levels, LICATS is a subacute, organ-specific pathology. It occurs days to weeks post-infusion and is temporally linked to B-cell depletion. Symptoms often mimic the patient’s original autoimmune disease but are generally mild and resolve spontaneously or with a short course of glucocorticoids. This distinction is vital, as LICATS should not be mistaken for a disease flare and does not necessitate the reintroduction of long-term immunosuppression. While its exact pathogenesis remains unclear, it is likely driven by local cytokine release, target cell killing, or a temporary disruption of tissue homeostasis as CAR T cells infiltrate affected organs to clear dead cells.

In contrast, Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) remains a significant systemic complication, affecting 20–60% of patients. Characterized by neuro-inflammatory markers and blood-brain barrier breakdown, ICANS manifests through a spectrum of symptoms—ranging from mild handwriting deterioration and speech hesitancy to severe aphasia, seizures, and fatal cerebral edema. Diagnosis is primarily clinical, supported by the Immune Effector Cell-Associated Encephalopathy (ICE) score. Management follows a severity-graded approach: grade 1 requires supportive care, while grades 2 through 4 necessitate escalating doses of corticosteroids, such as dexamethasone or methylprednisolone. Despite its potential severity, the prognosis is generally favorable, with most patients achieving full recovery.

Parallel to these clinical insights, the rheumatology community has standardized the nomenclature for Sjögren’s. Following the 2023 International Rome Consensus, the term “Sjögren disease” (SjD) is now preferred over “Sjögren syndrome.” The consensus recommends replacing the label “secondary” with “associated” when SjD occurs alongside another systemic autoimmune condition. While common clinical practice should focus on the unified term “Sjögren disease,” researchers are encouraged to maintain the distinction between primary and associated forms to ensure population homogeneity in scientific studies. These updates reflect a broader shift toward precision and clarity in both the treatment and classification of complex autoimmune pathologies.

Further reading:

1. Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease: an observational study. Hagen, Melanie et al.The Lancet Rheumatology, Volume 7, Issue 6, e424 – e433
2. Tallantyre EC, Evans NA, Parry-Jones J, et al. Neurological updates: neurological complications of CAR-T therapy. J Neurol. 2021;268:1544–54. https://doi.org/10.1007/s00415-020-10237-3.
3. Ramos-Casals, M., Baer, A.N., Brito-Zerón, M.d.P. et al.2023 International Rome consensus for the nomenclature of Sjögren disease. Nat Rev Rheumatol21, 426–437 (2025). https://doi.org/10.1038/s41584-025-01268-z