Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts. The amplified transcripts were cloned and sequenced. Substantial proportions of identical α-chain TCR transcripts were identified in AAA lesions of 4 of 5 patients, demonstrating that clonally expanded T cells are present in these AAA lesions. These results were statistically significant by the bimodal distribution. Three of 5 of these patients were typed by DNA-based HLA-typing and all three expressed DRB1 alleles containing the DRβGln70 amino acid residue that has been demonstrated to be associated with AAA. All three patients exhibited clonally expanded T cells in AAA lesions. Four of the 5 patients with AAA who exhibited clonal expansions of α-chain TCR transcripts, also exhibited clonal expansions of β-chain TCR transcripts in AAA lesions, as we have demonstrated previously (J Immunol 192:4897, 2014). αβ TCR-expressing T cells infiltrating AAA lesions contain T-cell clones which have undergone proliferation and clonal expansion in vivo in response to as yet unidentified specific antigens that may be self or nonself. These results provide additional evidence supporting the hypothesis that AAA is a specific antigen-driven T-cell autoimmune disease.
AAA is a life-threatening vascular disease and one of the ten leading causes of death of 55–74 years old men and women. Although autoimmunity may be responsible for the initiation and/or progression of the disease, limited information is available about the pathogenesis of AAA. Mononuclear infiltrates comprised mostly of T and B cells and monocytes are present in AAA lesions. We have reported (J. Immunol. 192:4897, 2014) that clonally expanded beta-chain TCR transcripts are present in AAA lesions, providing evidence suggesting that AAA is a specific antigen-driven T-cell disease. In addition to the beta-chain TCR, there are several reasons to study the clonality and the repertoire of the alpha-chain TCR in AAA. Alpha-chain TCR transcripts from AAA lesions from these patients were amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR and the amplified transcripts were cloned and sequenced. Sequence analysis revealed substantial proportions of identical alpha-chain TCR transcripts in 4 of 5 AAA patients, demonstrating that clonally expanded T cells are present in these AAA lesions. These results are statistically significant. These T-cell clones very likely have undergone proliferation and clonal expansion in vivo in response to specific, although, as yet unidentified, antigen(s) (self or non-self) recognized by the T-cell clones. Three of 5 patients with AAA were typed by DNA-based HLA-typing and all expressed DRB1 alleles positive for the DRbGln70 amino acid residue, reported to be associated with AAA. Clonally expanded T cells in AAA lesions were found in all these 3 patients. These findings provide additional evidence suggesting that AAA is a specific antigen-driven T-cell disease.
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