Proteomics evidence of specific IGKV1-8 association with cystic lung light chain deposition disease

Mylène Camus, Sandrine Hirschi, Grégoire Prevot, Marie-Pierre Chenard, Hervé Mal, Marc Stern, Martine Reynaud-Gaubert, Julia Gilhodes, Odile Burlet-Schiltz, Pierre Brousset and Magali Colombat

Key Points

  • Mass spectrometry-based proteomics is a powerful technique that can identify IGVL gene products from tissue specimens

  • High frequency of IGKV1-8 usage in cystic lung LCDD partially explains pulmonary tropism and argues for a distinct entity


We previously reported a new form of LCDD presenting as diffuse cystic lung disorder that differs from the usual systemic form, with respect to the age, the male/female ratio, the involved organs, and the hematologic characteristics. We also demonstrated that the light chains were produced by an intrapulmonary B-cell clone and, that this clone shared a stereotyped antigen receptor IGHV4-34/IGKV1. However, we analyzed only 3 patients. Herein, we conducted a retrospective study including lung tissue samples from 24 patients with pulmonary LCDD (pLCDD) matched with samples from 13 patients with pulmonary AL kappa amyloidosis used as controls. Mass spectrometry-based proteomics identified immunoglobulin kappa peptides as the main protein component of the tissue deposits in all patients. Interestingly, in pLCDD, IGKV1 was the most common kappa family detected (86.4%) and, IGKV1-8 was overrepresented compared with pulmonary AL kappa amyloidosis (75% vs 11.1%, p=0.0033). Furthermore, IGKV1-8 was predominantly associated with a diffuse cystic pattern (94%) in pLCDD. In conclusion, high frequency of IGKV1-8 usage in cystic pLCDD constitutes an additional feature arguing for a specific entity distinct from the systemic form that uses preferentially IGKV4-1.

  • Submitted January 22, 2019.
  • Revision received March 22, 2019.
  • Accepted March 19, 2019.