Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis

  title={Immunohistochemical analysis of anti-Hu-associated paraneoplastic encephalomyelitis},
  author={Fabi{\'a}n Bernal and Francesc Graus and {\`A}lex Pifarr{\'e} and Albert Saiz and Baya Benyahia and Teresa Ribalta},
  journal={Acta Neuropathologica},
Abstract. The precise immune mechanisms of neuronal death in anti-Hu-associated paraneoplastic encephalomyelitis (PEM) are unclear. We performed an immunohistochemical study on postmortem brain tissue from 11 patients with anti-Hu-associated PEM to further characterize the immune reaction and to ascertain possible mechanisms of neuronal death. To analyze inflammatory infiltrates, antibodies against lymphocyte subpopulations (CD3, CD20, CD4, CD8), macrophage and activated microglia (CD68), major… 
CD4+ and CD8+ T cells are both needed to induce paraneoplastic neurological disease in a mouse model
An animal model mimicking PND is developed and it is demonstrated that HA-expressing tumors, but not control tumors, induce in vivo activation, proliferation and differentiation of naïve HA-specific CD4+ and CD8+ T cells into effector cells.
Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis.
Findings strongly support a central role for T cell-mediated neuronal cytotoxicity in encephalitides with antibodies against intracellular antigens in voltage-gated potassium channel-complex encephalitis.
Paraneoplastic Neurological Syndromes associated with anti-Hu antibodies: are T lymphocytes involved or not?
The role of T cells was investigated by studying CSF and blood of Hu-PNS patients and the presence of HuD-specific CD8+ T cells in CSF could not be demonstrated, and more research is required to either confirm or reject a role for T lymphocytes in Hu- PNS.
Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma
Findings coupled with recently reported in vitro data showing that antibodies downregulate the levels of NMDA receptors suggest that the antibody immune-response is more relevant than cytotoxic T-cell mechanisms in the pathogenesis of anti-NMDAR-associated encephalitis.
Paraneoplastic encephalomyelopathies: pathology and mechanisms
The neuropathological findings and pathophysiology of paraneoplastic CNS disorders with reference to antigen-specific serology and neurological and oncological contexts are described.
No evidence for circulating HuD-specific CD8+ T cells in patients with paraneoplastic neurological syndromes and Hu antibodies
The results do not support a role for HuD-specific CD8+ T cells in Hu-PNS, and further studies should focus on the detection of circulating HuD and Class I HLA multimers in affected tissues.
Imbalances in circulating lymphocyte subsets in Hu antibody associated paraneoplastic neurological syndromes
Analysis of circulating lymphocyte subsets in untreated patients with SCLC, PNS and Hu antibodies provides further support for the involvement of T cells in the pathogenesis of Hu antibody associated PNS.
Cell-Mediated Immune Responses in Paraneoplastic Neurological Syndromes
The link between PNS emergence and antitumor responses may result from more active CTLs and less functional Treg lymphocytes, which often coincide with a less aggressive course of neoplastic disease.


T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis
Findings suggest that an antigen-driven oligoclonal cytotoxic T-cell response plays a role in the pathogenesis of anti-Hu associated PEM/SN.
Cell‐mediated autoimmunity in paraneoplastic neurological syndromes with anti‐Hu antibodies
Results indicate that HuD protein is an antigenic target for autoreactive CD4+ T cells, presumably of the Th1 subtype, which could therefore be directly involved in cell‐mediated injury of the nervous system as well as in antitumoral immunity.
Immunohistochemical analysis of the immune reaction in the nervous system in paraneoplastic encephalomyelitis
Frozen sections of frontal cortex, medulla, and dorsal root ganglia from a patient with small-cell lung cancer and paraneoplastic encephalomyelitis are examined and an antineuronal antibody (anti-Hu) is detected in the serum and CSF of the patient and deposits of IgG in the periphery of some neurons in dorsalRoot ganglia are found.
Analysis of the IgG subclass distribution and inflammatory infiltrates in patients with anti‐Hu‐associated paraneoplastic encephalomyelitis
It is concluded that anti-Hu-associated PEM/PSN is a complex immune disorder in which both cell-mediated and humoral (probably non-CMT and non-ADCC) cytotoxic mechanisms appear to be involved in its pathogenesis.
Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients.
The predictors of mortality and PEM evolution found in the study may be important in the design of future therapeutic protocols, and emphasize the importance of early diagnosis and treatment of the underlying tumour.
Anti-Hu-associated paraneoplastic sensory neuropathy and breast cancer
A patient with breast carcinoma presenting with a muscle metastasis and an Hu-Ab associated PSN is described, suggesting that the metastasis probably triggered the Hu-mediated immune response that led to the PSN.
The inflammatory reaction of paraneoplastic ganglionitis and encephalitis: an immunohistochemical study
Tissues from two patients with small cell carcinoma of the lung and paraneoplastic neurological syndromes were studied, suggesting a T-cell-mediated immune attack in paranoplastic ganglionitis and encephalitis, with a greater role for macrophages in ganglIONitis.
Major Histocompatibility Complex Molecule Expression in the Human Central Nervous System: Immunohistochemical Analysis of 40 Patients
  • R. Sobel, M. Ames
  • Biology, Medicine
    Journal of neuropathology and experimental neurology
  • 1988
In the human CNS, regulation of expression of MHC molecules is complex, can be affected by age, regional anatomy, and by local or remote CNS lesions, and may influence patterns and degrees of T cell immune responses.
Immunization with the paraneoplastic encephalomyelitis antigen HuD does not cause neurologic disease in mice
Ind immunized SJL/J mice, Lewis rats, and Hartley guinea pigs with purified recombinant HuD fusion protein with high-titer anti-HuD antibodies and apparent uptake of purified IgG by neurons in the brain proved to be artifactual.