T-cell receptor analysis in anti-Hu associated paraneoplastic encephalomyelitis

    loading  Checking for direct PDF access through Ovid

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.

Related Topics

    loading  Loading Related Articles