Akihiro Hoshino, Japan
Tokyo Medical and Dental University Department of Pediatrics and Developmental BiologyPresenter of 1 Presentation
PLASMACYTOMA-LIKE POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER WITH MULTIPLE AUTOANTIBODIES IN A XIAP DEFICIENT PATIENT
Abstract
Background and Aims
Plasmacytoma-like post-transplant lymphoproliferative disorder is a rare form of post-transplant lymphoproliferative disorder (PTLD), which is of plasma-cell origin. Its etiology remains unclear because of its rare presentation.
Methods
A XIAP deficient patient developed recipient-derived EBV-negative plasmacytoma-like PTLD with multiple autoimmune diseases. Immunological and genetic analyses were performed including high-throughput sequencing of immunoglobulin heavy-and light-chain genes using total RNA from PTLD cells.
Results
The histopathologic analyses of PTLD cells were positive for IgG and lambda light-chain. Several serum autoantibodies were also restricted in the IgG and lambda light-chain, suggesting that these autoantibodies were produced by PTLD cells. Repertoire analysis revealed a clonal expansion of IGHV3-33/IGHD7-27/IGHJ5 in IGH and IGLV1-47/IGLJ3 in IGL. While the IGH and IGL sequences were predominant in one and two subclone, respectively, other multiple subclonal variants were also identified. Most constant regions consisted of IGHG4, but a small fraction consisted of IGHG1, IGHG3, IGHA2, IGHE and IGHM. The frequency of somatic hypermutation (SHM) was significantly reduced, with only 1.3 ± 0.9 and 1.7 ± 1.1 mutations in IGHV and IGLV, respectively.
Conclusions
The plasmacytoma-like PTLD cells were found to originate from a germinal center B cell exposed to on-going class switch recombination but lack SHM, and committed to be a plasma cell. Decreased SHM frequency is in contrast to the high frequency in non-PTLD myeloma cells, which may contribute to the production of autoantibodies. This study provides new insights into the etiology of EBV-negative PTLD and autoimmune diseases in immunodeficient patients.