Ultrastructural correlation with immunofluorescent stains in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)

Document Type

Conference Proceeding

Publication Date

3-2026

Publication Title

Laboratory Investigation

Abstract

Background: Approximately 1/3 of PGNMID lacks serologic or bone marrow evidence of monoclonal proteins. In addition to monoclonal immunofluorescent (IF) staining and restricted IgG subtyping, corresponding electron microscopy (EM) may aid in confirming the diagnosis. In contrast to the granular IF staining in immune complex diseases, positive IF stains in PGNMID demonstrate a linear smear pattern due to the deposition of loosely unbound monoclonal proteins. This study aimed to characterize the ultrastructural features of monoclonal protein deposits in PGNMID and correlate them with IF findings. Design: We retrospectively reviewed EM images from 21 renal biopsies of PGNMID in 19 patients collected over the past 10 years. One EM case lacked available EM data. Lupus nephritis cases (n = 53) served as controls. Characteristic features of monoclonal deposits in glomeruli were summarized. Results: The ages of patients with PGNMID ranged from 35 to 89 years old (Table 1), with 11 females, and 8 males. Additional clinical and morphologic data are presented in Table 1. In correlation with the linear smear pattern by IF staining in PGNMID, we identified two major patterns and two minor patterns of electron-dense deposits at the ultrastructural level. In 20/20 of PGNMID biopsies, the electron dense materials revealed fibrinlike (F) deposits along subendothelial spaces (smooth contours with homogeneous fine granular appearance rather than humpy and bumpy immune complex deposits (Figure panels #1 and #2, Table 1). Subendothelial edematous changes (E) were noted in 11/ 20 cases (Panels 1 and 3). Two minor changes included detached monoclonal proteins (D) floating in the glomerular capillary spaces in 7/20 (Panels 4 and 5) and a layered deposit pattern (L) resembling sand precipitation in 5/20 biopsies (Panel 6). Conclusions: Our data indicates that monoclonal protein deposits in PGMID typically present as unbound protein precipitation with a homogenous fibrin-like patten with smooth borders, predominantly located in the subendothelial spaces of glomeruli. These features correlate well with the linear smear pattern seen on IF staining. Additional EM features that support the diagnosis of PGMID include endothelial edematous changes, detached protein fragments in the glomerular lumen and a layered deposition pattern.

Volume

106

Issue

3 Suppl 1

First Page

105740

Comments

USCAP (United States and Canadian Academy of Pathology) 115th Annual Meeting, March 21-26, 2026, San Antonio, TX

Last Page

105740

DOI

10.1016/j.labinv.2025.105740

Link to Full Text

Share

COinS