Targeting CD19 in Autoimmune Neuropathy: Case Report Insights

Two patients with disabling, treatment-resistant autoimmune neuropathies showed marked and sustained clinical improvement after receiving CD19-directed CAR T-cell therapy, according to a case report published in The Lancet Neurology in July 2025. These findings offer the first clinical evidence that chimeric antigen receptor T-cells may induce deep remission in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and related disorders where standard immunotherapies have failed.

Here’s a quick look at the case report.

Clinical Recovery After Exhausted Options

The first patient, a 72-year-old man with a motor variant of CIDP, had progressed toward symmetric tetraplegia despite multiple treatments, including corticosteroids, immunoglobulin, plasma exchange, rituximab, and bortezomib. The second, a 54-year-old man with anti-NF-155 positive paranodopathy, had become wheelchair-dependent due to disabling tremor, despite receiving all standard therapies.

Each patient underwent leukapheresis, lymphodepletion, and infusion of autologous CD19 CAR T-cells. Peak T-cell expansion occurred within the first two weeks.

Cytokine release syndrome developed in both patients but was manageable with standard interventions. One patient experienced a brief episode of mild neurotoxicity, which resolved without treatment.

Sustained Neurologic and Biomarker Gains

By six months after infusion, Patient One had regained sufficient strength to perform squats and upper body exercises. The patient’s walking distance increased, and the Overall Disability Sum Score improved. Serum neurofilament light chain (sNfL), a marker of axonal injury, normalized in parallel with symptom improvement and nerve conduction recovery.

Patient Two progressed from being wheelchair-bound to walking independently over 200 meters within four months. Tremor resolved, sNfL levels normalized, and functional scores improved.

Both patients cleared circulating autoantibodies—anti-GM1 in the first and anti-NF-155 in the second—within ten and four months, respectively. All prior immunotherapies were successfully discontinued.

Why Target CD19?

The results support the mechanistic rationale for targeting CD19, a surface marker present not only on naïve and memory B cells but also on plasmablasts, which are typically resistant to rituximab. By achieving deep and sustained B-cell depletion, including antibody-producing populations, CAR T-cell therapy may interrupt the autoimmune cascade that drives axonal injury in CIDP and related neuropathies.

Weighing Safety and Durability

When it comes to side effects, they were manageable in these case reports. Transient hypogammaglobulinemia was addressed with immunoglobulin replacement, and no relapses occurred during ten months of follow-up. While these findings are encouraging, the small sample size and absence of a control arm limit generalizability.

Toward a Single-Treatment Model

One of the most notable findings is the durability of effect after a single infusion. In contrast to maintenance therapies such as FcRn or complement inhibitors, CAR T-cells may offer long-term remission with a single intervention. If validated, this would mark a fundamental shift in the treatment strategy for autoimmune neuropathies.

Looking Ahead

Moving forward, the authors call for controlled clinical trials to determine optimal patient selection, long-term immune outcomes, and cost-effectiveness. These cases suggest that for select patients with advanced, treatment-refractory neuropathy, CD19-directed CAR T-cells may provide an effective path when no other options remain.

Reference:
Motte J, Klimas R, Sgodzai M, et al. CD19-targeted CAR T-cell therapy for treatment-refractory autoimmune neuropathies. Lancet Neurol. 2025;24(7):564-566. doi:10.1016/S1474-4422(25)00199-1