T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis Journal Article
| Authors: | Voltz, R.; Dalmau, J.; Posner, J. B.; Rosenfeld, M. R. |
| Article Title: | T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis |
| Abstract: | Objective: To analyze the T-cell receptor (TCR) repertoire in the inflammatory infiltrates of the nervous system and tumor of patients with anti-Hu associated paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). Background: In PEM/SN, the pathogenic role of the infiltrating T cells is speculative. TCR analysis may establish whether these lymphocytes are attracted nonspecifically by a proinflammatory environment or are driven by a specific antigen or superantigen. Methods: We examined frozen tissues of seven patients with PEM/SN using immunohistochemical and PCR analysis. Of 62 tissue blocks from seven patients, 19 blocks from five patients had >100 CD3+ cells per section infiltrating the nervous system or tumor. These infiltrates allowed screening of the TCR Vβ family repertoire using a panel of 18 antibodies that recognize family-specific regions of most TCR Vβ families against which antibodies have been generated. To distinguish between antigen- driven clonal and superantigen-driven family expansion, we extracted RNA from frozen tissue and performed reverse transcriptase (RT)-PCR analysis followed by subcloning and sequencing of the antigen-specific CDR3 region of the TCR Vβ chain. Results: All five patients showed a limited Vβ repertoire. An overrepresentation (> 10% of total CD3+) of certain Vβ families was identified in three patients (as high as 45% of total CD3+), which consisted mainly of CD8+ cells. CDR3 sequences obtained from one patient revealed an in situ expansion of two clones in the amygdala (one at a frequency of 57%) and four clones in the tumor. Conclusion: These findings suggest that an antigen- driven oligoclonal cytotoxic T-cell response plays a role in the pathogenesis of anti-Hu associated PEM/SN. |
| Keywords: | immunohistochemistry; adult; clinical article; human tissue; aged; aged, 80 and over; middle aged; unclassified drug; brain neoplasms; cd3 antigen; cd8 antigen; antigens, cd3; reverse transcription polymerase chain reaction; lung neoplasms; nerve tissue proteins; rna-binding proteins; t lymphocyte receptor; reverse transcriptase polymerase chain reaction; t-lymphocytes, cytotoxic; dna, neoplasm; inflammatory infiltrate; paraneoplastic syndrome; hu paraneoplastic encephalomyelitis antigens; receptors, antigen, t-cell, alpha-beta; carcinoma, small cell; cerebellar nuclei; cancer antibody; amygdala; ganglia, spinal; encephalomyelitis; paraneoplastic syndromes; complementarity determining region; olivary nucleus; humans; human; male; female; priority journal; article; hu antibody |
| Journal Title: | Neurology |
| Volume: | 51 |
| Issue: | 4 |
| ISSN: | 0028-3878 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 1998-10-01 |
| Start Page: | 1146 |
| End Page: | 1150 |
| Language: | English |
| PUBMED: | 9781545 |
| PROVIDER: | scopus |
| DOI: | 10.1212/WNL.51.4.1146 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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