Elsevier

The Lancet

Volume 363, Issue 9408, 14 February 2004, Pages 525-531
The Lancet

Mechanisms of Disease
Castleman's tumours and production of autoantibody in paraneoplastic pemphigus

https://doi.org/10.1016/S0140-6736(04)15539-6Get rights and content

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.

Introduction

Paraneoplastic pemphigus is an autoimmune mucocutaneous disorder, characterised by an associated neoplasm and the presence of a unique IgG autoantibody that recognises epidermal proteins.1, 2, 3, 4, 5 Neoplasms associated with the disease are often of lymphocytic origin and include non-Hodgkin's lymphoma,6, 7 chronic lymphocytic leukaemia,1, 8 and Castleman's disease.9, 10, 11, 12, 13 One of the characteristic features of paraneoplastic pemphigus associated with Castleman's disease and other benign tumours is the remarkable improvement in symptoms noted after removal of the tumour.11, 12, 13, 14 In some individuals accompanied bronchiolitis obliterans occasionally may result in respiratory failure and death.9, 10

The role of the neoplasm in the pathogenesis of paraneoplastic pemphigus is controversial, with detailed data unavailable possibly because of the limited number of affected individuals. Clinically, an IgG autoantibody against epidermal proteins is often used as a diagnostic marker for the disease,15, 16 but might also be involved in autoimmune injuries.1, 5 Our aim was to ascertain the mechanism by which the autoantibody is generated and to investigate the possible role of Castleman's tumours in the process.

Section snippets

Participants

We included in our analyses seven patients with paraneoplastic pemphigus associated with localised hyaline vascular-type Castleman's tumours who were diagnosed and treated at the Department of Dermatology, Peking University First Hospital between May, 1999, and December, 2002.

The patients all had clinically similar lesions of pemphigus vulgaris, pemphigus erythematosus, and lichen planus (figure 1). Histological examination of the cutaneous lesions indicated epidermal acantholysis or

Results

The table shows the characteristics of the seven patients, most of whom responded badly or only partially to routine treatment, including corticosteroids and other immunosuppressive drugs. After resection of Castleman's tumours, however, cutaneous lesions improved gradually and disappeared within 6–11 weeks without recurrence in the six patients with paraneoplastic pemphigus (figure 2), and erosions of the mucosa and ulcers also improved. However, mucosal lesions recovered only slowly, and one

Discussion

Our findings suggest that Castleman's tumours are involved in the production of autoantibodies in patients with paraneoplastic pemphigus, and that this production is important in the pathogenesis of the disease. As previously reported,20, 21 our findings indicate a close relation between the presence of a Castleman's tumour and the mucocutaneous manifestations seen in patients with paraneoplastic pemphigus, which do not respond to routine immunosuppressive treatment but resolve rapidly after

GLOSSARY

complementarity determining region
The heavy and light chains of antibodies each contain three regions of hypervariability, termed complementarity determining regions (CDR), which interact with antigen.

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