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MECHANISMS OF DISEASE
Summary
Background Paraneoplastic pemphigus is an autoimmune
mucocutaneous disease associated with Castleman’s
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
Castleman’s tumours in production of the autoantibody and
pathogenesis of paraneoplastic pemphigus.
Methods We enrolled seven patients with paraneoplastic
pemphigus associated with Castleman’s 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 Castleman’s
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