Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease

Yannick Dieudonné; Marc-Antoine Silvestrini; Antoine Dossier; Véronique Meignin; Fanélie Jouenne; Thibault Mahévas; Jean-David Bouaziz; Margaret A Jackson; Pierre Mordant; Justine Poirot; Fanny Onodi; Julien Calvani; Muriel Hourseau; Diane Evrard; Mirlinda Berisha; François Perrin; Claire Danel; Raphael Borie; Lionel Galicier; Samia Mourah; Djaouida Bengoufa; Eric Oksenhendler; Sabine Grootenboer-Mignot; David Boutboul

doi:10.1111/bjh.18847

Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease

Br J Haematol. 2023 Jul;202(2):267-278. doi: 10.1111/bjh.18847. Epub 2023 May 23.

Authors

Yannick Dieudonné^{1

2}, Marc-Antoine Silvestrini³, Antoine Dossier⁴, Véronique Meignin⁵, Fanélie Jouenne⁶, Thibault Mahévas⁷, Jean-David Bouaziz⁷, Margaret A Jackson³, Pierre Mordant⁸, Justine Poirot³, Fanny Onodi³, Julien Calvani⁵, Muriel Hourseau⁹, Diane Evrard¹⁰, Mirlinda Berisha¹¹, François Perrin¹², Claire Danel⁹, Raphael Borie¹³, Lionel Galicier^{11

14}, Samia Mourah⁶, Djaouida Bengoufa¹⁵, Eric Oksenhendler^{11

14}, Sabine Grootenboer-Mignot¹⁶, David Boutboul^{3

11

14}

Affiliations

¹ Department of Clinical Immunology and Internal Medicine, National Reference Centre for Systemic Autoimmune Diseases (CNR RESO), Strasbourg University Hospital, Strasbourg, France.
² INSERM UMR-S1109, Université de Strasbourg, Strasbourg, France.
³ U976 HIPI, Hôpital Saint Louis, Université Paris Cité, Paris, France.
⁴ Department of Internal Medicine, Hôpital Bichat, Université Paris Cité, Paris, France.
⁵ Department of Pathology, Hôpital Saint Louis, Université Paris Cité, Paris, France.
⁶ Laboratoire de Génomique des Tumeurs et Pharmacologie, INSERM UMR-S976, Hôpital Saint Louis, Université Paris Cité, Paris, France.
⁷ Department of Dermatology, Hôpital Saint Louis, Université Paris Cité, Paris, France.
⁸ Department of Thoracic Surgery, Vascular Surgery, and Lung Transplantation, Hôpital Bichat, Université Paris Cité, Paris, France.
⁹ Department of Pathology, Hôpital Bichat, Université Paris Cité, Paris, France.
¹⁰ Department of Otorhinolaryngology, Hôpital Bichat, Université Paris Cité, Paris, France.
¹¹ National Reference Centre for Castleman Disease, Hôpital Saint Louis, Université Paris Cité, Paris, France.
¹² Department of Internal Medicine, Centre Hospitalier de Saint-Nazaire, Saint-Nazaire, France.
¹³ Inserm, PHERE, F-75018 Paris, et Hôpital Bichat, APHP, Service de Pneumologie A, FHU APOLLO, Université Paris Cité, Paris, France.
¹⁴ Clinical Immunology Department, Hôpital Saint Louis, Université Paris Cité, Paris, France.
¹⁵ Immunology laboratory, Hôpital Saint Louis, Université Paris Cité, Paris, France.
¹⁶ Department of Immunology, Auto-Immunity and Hypersensitivity, Hôpital Bichat, Université Paris Cité, Paris, France.

PMID: 37221131
DOI: 10.1111/bjh.18847

Abstract

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.

Keywords: paraneoplastic pemphigus; periplakin epitope mapping; unicentric Castleman disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies
Castleman Disease* / pathology
Humans
Myasthenia Gravis* / diagnosis
Paraneoplastic Syndromes* / diagnosis
Paraneoplastic Syndromes* / etiology
Pemphigus* / diagnosis
Pemphigus* / etiology

Substances

Autoantibodies