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

We previously reported a new form of light chain deposition disease (LCDD) presenting as diffuse cystic lung disorder that differs from the usual systemic form with respect to patient 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 only analyzed 3 patients. We conducted a retrospective study including lung tissue samples from 24 patients with pulmonary LCDD (LCDD) matched with samples from 13 patients with pulmonary κ light chain amyloidosis (AL amyloidosis) used as controls. Mass spectrometry-based proteomics identified immunoglobulin κ peptides as the main protein component of the tissue deposits in all patients. Interestingly, in LCDD, IGKV1 was the most common κ family detected (86.4%), and IGKV1-8 was overrepresented compared with AL amyloidosis (75% vs 11.1%, = .0033). Furthermore, IGKV1-8 was predominantly associated with a diffuse cystic pattern (94%) in LCDD. In conclusion, the high frequency of IGKV1-8 usage in cystic LCDD constitutes an additional feature arguing for a specific entity distinct from the systemic form that preferentially uses IGKV4-1.