Oligoclonal Expansion of Cd8+ T Cells during Idiopathic Multicentric Castleman Disease Flares Suggests an Antigen Driven Process
| Autor: | Dustin Shilling, David C. Fajgenbaum, Eline T. Luning Prak, Jason Stadanlick, Wenzhao Meng, Vera P. Krymskaya, Evgeniy Eruslanov, Abhishek Rao |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Blood. 132:2411-2411 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2018-99-118650 |
| Popis: | Castleman disease (CD) describes a group of heterogeneous diseases defined by shared characteristic lymph node histopathology and is classified based on the number of regions of enlarged lymph nodes. Multicentric CD (MCD) involves multiple regions of lymphadenopathy as well as systemic inflammation, cytopenias, and vital organ dysfunction due to a cytokine storm that often includes interleukin-6. In ~50% of patients, the pathogenic driver is Kaposi sarcoma-associated/human herpesvirus-8 (HHV-8) in the context of immunosuppression. In contrast, the etiologic driver in HHV8-negative MCD (idiopathic or iMCD) is unknown. To date, most research has focused on descriptive characterization of the enlarged lymph nodes, and the pathological cell types driving iMCD pathogenesis remain unidentified. Given that lymphoid cells circulate through the blood and lymph nodes, are able to produce high levels of cytokines upon activation, and are the primary cell types responsible for the enlarged lymph nodes in iMCD and other related diseases, we first performed a detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) obtained from iMCD patients in remission (n=16), iMCD patients during disease flare (n=6) and healthy donors (HD) (n=15). PBMCs were isolated by density gradient and either stained immediately or cryopreserved for future analyses. A HD sample was drawn at the same time as each experimental sample and processed and analyzed in parallel. Our initial hypothesis was that analysis of iMCD flare PBMCs would reveal an abnormal myeloid or lymphocyte subset. Thus, we stained and analyzed PBMCs for standard lineage markers: CD11b, CD15, CD19, CD3, CD56 and CD14. However, we observed no gross differences in population frequencies during either remission or flare compared to HD. Additionally, no differences in the proportions of natural killer T cells (CD3+CD56+), or CD4+ or CD8+ lymphocytes were observed. However, more refined examinations of the lymphocyte sub-sets based upon activation status revealed an increased proportion of activated memory (CD62LlowHLA-DR+) CD8+ cells during iMCD flare compared to HD and iMCD patients in remission and a decreased proportion of naïve (CD62L+CD45RA+) CD8+ cells compared to HD (p Disclosures Fajgenbaum: Janssen Pharmaceuticals, Inc.: Research Funding. |
| Databáze: | OpenAIRE |
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