Castlemanʹs tumours and production of autoantibody in paraneoplastic pemphigus

Background Paraneoplastic pemphigus is an autoimmune mucocutaneous disease associated with Castlemanʹs tumours, which when surgically removed often result in great improvement of mucocutaneous lesions. An IgG autoantibody against epidermal proteins is often used as a diagnostic marker for disease. Our aim was to ascertain the role of Castlemanʹs tumours in production of the autoantibody and pathogenesis of paraneoplastic pemphigus. Methods We enrolled seven patients with paraneoplastic pemphigus associated with Castlemanʹs disease and assessed the effect of removal of tumours on mucocutaneous lesions in six individuals and on autoantibody titre with indirect immunofluorescence in four patients. We cultured tumour cells from one patient and assayed the secreted autoantibody. Finally, we characterised the gene sequence and expression of the variable region of the immunoglobulin heavy chain (IgVH) in tumour B cells from all patients by reverse transcription-PCR, DNA sequencing, and in-situ hybridisation. Findings Cutaneous lesions disappeared within 6–11 weeks after resection of tumours. Mucosal lesions also improved in this period, but lasted for 5–10 months overall. Autoantibody titre decreased and became undetectable within 5–9 weeks in three of four patients assessed. We identified secreted autoantibody, similar to that identified in patients’ serum, in cultured tumour cells. The tumour B-cells of the seven patients shared and expressed two rearrangement patterns of complementarity determining region 3 (CDR3) of IgVH. Interpretation Secreted autoantibody from Castlemanʹs tumours, which reacts against epidermal proteins, could be an essential factor in the pathogenesis of paraneoplastic pemphigus. We noted clonal rearrangement, resulting in similar variable regions of IgVH, in tumour B cells isolated from all seven patients. However, whether this pattern is associated with autoimmunity remains to be ascertained.