Immunopathogenesis of paraneoplastic neurological syndromes associated with anti-Hu antibodies

Abstract

Paraneoplastic neurological disorders (PNDs) are syndromes that develop in cancer patients when an efficient antitumor immune response, directed against antigens expressed by both malignant cells and healthy neurons, damages the nervous system. Herein, we analyze existing data on the mechanisms of loss of self tolerance and nervous tissue damage that underpin one of the most frequent PNDs, the anti-Hu syndrome. In addition, we discuss future directions and propose potential strategies aimed at blocking deleterious encephalitogenic immune responses while preserving the antineoplastic potential of treatment.

Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report

“…The positive outcome described herein may be attributed to the addition of plasmapheresis to the treatment regimen, which may have exerted a synergistic effect. Interestingly, however, it has been demonstrated that plasmapheresis reduces anti-Hu antibody levels in the serum, but not in the CSF (10). Unlike the majority of previous reports of imminent death from progressive PNS, the patient described herein has achieved steady recovery of the neurological status over the course of the past 45 months since the first presentation of neurological deficit, and has remained stable.…”

“…A number of experimental studies have suggested that cytotoxic T cells may be the main effectors of the immune response (32). This T-cell mediated response may result in neuronal cell death and axonal degeneration that are extremely difficult to treat (32,33). It remains unclear, however, why only some SCLC patients develop PNS, given that the HuD antigen is constantly expressed by these tumour cells (29).…”

“…Detectable levels of circulating anti-Hu antibodies may be found in ~20% of SCLC patients, although not all will develop PNS (5,9). It remains Synchronous Adie's syndrome and type 1 antineuronal nuclear antibody (anti-Hu)-related paraneoplastic neurological syndromes as predictors of complete response in limited-stage small-cell lung cancer: A case report unclear why only some SCLC patients develop PNS (10). It has been hypothesized that these ectopic neuronal antigens are recognized by the immune system as foreign, triggering the production of ANNA-1 with consequential paraneoplastic effects manifesting clinically with various degrees of severity and neurological symptoms (7,8).…”

Migration et pathogénicité des lymphocytes T CD8 dans les maladies du système nerveux central

“…Les syndromes neurologiques paranéoplasiques sont étroitement liés au développement d'une réponse immunitaire antitumorale dirigée contre des antigènes communs aux cellules cancéreuses et au système nerveux, appelés antigènes onconeuronaux. Cette réponse est responsable de dommages tissulaires du système nerveux central [12]. Parmi les syndromes neurologiques paranéoplasiques, le plus fréquent et le mieux documenté est le syndrome anti-Hu.…”

CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model

“…1 PNDs are the best-documented examples showing a direct link between naturally occurring immunity against malignancy and autoimmunity. 2 However, the immune actors involved in these 2 phenomena remain to be determined.…”