Isolated Peripheral Nervous System Presentation in Ma/Ma2-Associated Autoimmunity

Our plain-English summary of Isolated Peripheral Nervous System Presentation in Ma/Ma2-Associated Autoimmunity, by A. Vilaseca, M. Villagrán-García, A. Farina, et al (Neurology® Neuroimmunology & Neuroinflammation, 2026).

The study

• Authors: A. Vilaseca, M. Villagrán-García, A. Farina, J. Bruna, J.O. Dalmau, D. Dubey, J. Honnorat, F. Graus
• Journal: Neurology® Neuroimmunology & Neuroinflammation
• Published: 2026;13(5):e200623
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: Ma/Ma2-associated neurologic autoimmunity is characterized by CNS involvement. However, isolated peripheral nervous system (PNS) presentations have been rarely reported. We aimed to describe the frequency and syndromes of patients with Ma/Ma2 antibodies and isolated PNS involvement.

Methods: We performed a nested case series within multicenter cohorts of patients with Ma/Ma2-associated neurologic syndromes, confirmed by tissue-based assay and line-blot. Patients with isolated PNS presentations were included.

Results: Among 212 patients with Ma/Ma2 antibody-associated neurologic syndromes, 7 (3%) presented with isolated PNS involvement (median age, 68 years; 4/7 female). PNS syndromes included sensory neuronopathy (3 patients), myeloradiculopathy (1), radiculoplexopathy (1), motor neuronopathy (1), and multiple mononeuropathy. All patients were anti-Ma2-positive, whereas Ma antibodies (reactive against Ma1 and Ma2 proteins) were detected in 2 (33%)/6 tested patients. An associated cancer was identified in 6 (86%)/7 patients: pleural mesothelioma; oral squamous cell; testicular, lung, and breast cancer; and B-cell lymphoma. Five patients received immunotherapy, cancer treatment, or both. After a median follow-up of 23 months, symptoms improved or stabilized in 3 patients and progressed in 4.

Discussion: Isolated PNS involvement is a rare manifestation of Ma/Ma2 associated autoimmunity. Ma/Ma2 antibody testing should be considered in neuronopathies and unexplained non-length-dependent neuropathies.

In plain English

This short report described a nested case series. It drew on retrospective chart review of patients at Hospital Clinic in Barcelona, a French reference center in Lyon, and Mayo Clinic in Minnesota. All had nervous-system disease linked to Ma/Ma2 antibodies, which are immune proteins that react with nerve-cell proteins. Of 212 such patients, 7 (3%) had a presentation mainly in the peripheral nerves, the nerves outside the brain and spinal cord; one of them also had spinal cord involvement. Their median age was 68, and 4 of the 7 were women. Six of the 7 had a cancer: pleural mesothelioma, oral squamous cell carcinoma, testicular, lung and breast cancer, and B-cell lymphoma. The patient with pleural mesothelioma, a man aged 50 to 60, had a disorder of the nerve roots and nerve plexus. He received only symptom treatment and died from the cancer, with his nerve symptoms worse. The article does not mention asbestos or any patient's exposure history. Over a median 23 months, symptoms improved or stabilized in 3 patients and progressed in 4. The authors concluded that this presentation is rare.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nested case series within multicenter cohorts, based on retrospective chart review with descriptive statistics
• Who was studied: 7 of 212 patients with Ma/Ma2 antibody-associated neurologic syndromes. Each had an isolated peripheral nervous system presentation, with or without spinal cord involvement as long as the peripheral nervous system involvement predominated. Patients came from Hospital Clinic (Barcelona, Spain), the French Reference Center in Lyon, and Mayo Clinic (Minnesota). Median age was 68 (range 46 to 80), and 4 of 7 were female. Study dates are not stated.
• Exposure: The study does not examine asbestos or any fiber exposure. It concerns patients with Ma/Ma2 antibodies confirmed by tissue-based assay and line-blot. No exposure history is reported for the patient with pleural mesothelioma.
• Main results:
  • Among 212 patients with Ma/Ma2-associated neurologic syndromes, 7 (3%) had isolated peripheral nervous system involvement. One of these 7 also had spinal cord involvement.
  • The 7 patients had these syndromes: sensory neuronopathy (3), myeloradiculopathy (1), radiculoplexopathy (1), motor neuronopathy (1) and multiple mononeuropathy (1).
  • All 7 patients were positive for Ma2 antibodies. Ma antibodies were found in 2 of 6 tested patients (33%).
  • 6 of 7 patients (86%) had an associated cancer. The two patients with Ma antibodies had pleural mesothelioma and oral squamous cell carcinoma. The others had testicular, lung and breast cancer and B-cell lymphoma.
  • The patient with pleural mesothelioma had a radiculoplexus neuropathy and received symptomatic treatment. This patient died from cancer at 6 months of follow-up, with the neuropathy symptoms worse.
  • Among the 6 patients with confirmed cancer, the neurologic syndrome came before the cancer diagnosis or relapse in 5 (83%). The median delay to cancer diagnosis was 9 months (range 0 to 23 months).
  • At last follow-up (median 23 months, range 6 to 84), symptoms had improved or stabilized in 3 patients and progressed in 4. Two patients died from cancer progression.
• The authors' conclusion: The authors concluded that isolated peripheral nervous system involvement is a rare manifestation of Ma/Ma2-associated autoimmunity. They said Ma2 antibody testing should be considered in unexplained neuronopathies and non-length-dependent neuropathies.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Squamous Cell Carcinoma, Immunotherapy.

Related studies

• Lung function and nervous system involvement in asbestosis — O. Korhonen, J. Juntunen, et al. (1983)
• Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors — A. Vogrig, M. Fouret, et al. (2019)
• A Rare Clinical Presentation of Malignant Pleural Mesothelioma With Central Nervous System Metastases: A Case Report — M.A. Miernik-Skrzypczak, E. Misztela-Lisiecka, et al. (2025)
• Silicosis and autoimmunity — S. Lee, H. Hayashi, et al. (2017)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Malignant mesothelioma and central nervous system metastases. Report of two cases, pooled analysis, and systematic review — A.C. Miller, M. Miettinen, et al. (2014)

Browse return to medical research.