Single-cell sequencing reveals dynamic immune features of paraneoplastic pemphigus in a patient with follicular lymphoma

Objective: This study aims to elucidate the cellular and molecular mechanisms of PNP, particularly when it occurs secondary to lymphoma, by analyzing the dynamic immune landscape throughout the course of treatment.

Method

We performed single-cell transcriptome sequencing and single-cell T cell receptor (TCR) analysis on peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs) obtained from a patient with follicular lymphoma (FL) accompanied by PNP. Samples were collected at three critical time points: before treatment, during treatment, and after successful treatment. Result: Before treatment, we observed a specific enrichment of ITGAL+ T cells, abnormal γδT cell subtypes, and BCL2+ B cells in PBMCs.

Notably, naïve T cells and an abnormal B cell subtype were also enriched in BMCs. The single-cell transcriptome results mapped the lymphoma-associated tumor microenvironment and revealed post-treatment immune reconstitution. This reconstitution involved activated DNA damage and T cell immune responses, which was further supported by the observation of a gradually expanded TCR clone as the treatment progressed.

Conclusion: Our study delineates the dynamic immune landscape in a patient with FL-associated PNP throughout treatment, demonstrating that successful treatment correlates with immune reconstitution involving specific T cell responses and TCR clone expansion. These findings provide novel insights into the cellular and molecular mechanisms of PNP, especially in cases secondary to lymphoma.