Clinical significance of exostosin 1 in confirmed and suspected lupus membranous nephropathy

Lupus Sci Med. 2023 Dec 28;10(2):e001051. doi: 10.1136/lupus-2023-001051.

Abstract

Objective: This study aimed to investigate the clinical significance of exostosin 1 (EXT1) in confirmed and suspected lupus membranous nephropathy (LMN).

Methods: EXT1 was detected in 67 renal tissues of M-type phospholipase A2 receptor (PLA2R)-negative and ANA-positive membranous nephropathy by immunohistochemistry, and cases were divided into confirmed LMN and suspected LMN. The clinicopathological data were compared among the above groups, as well as EXT1-positive group and EXT1-negative group.

Results: Twenty-two cases (73.3%) of confirmed LMN and six cases (16.2%) of suspected LMN exhibited EXT1 expression on the glomerular basement membrane and/or mesangium area, showing a significant difference (p<0.001). Concurrently, lupus nephritis (LN) of pure class V demonstrated a lower frequency of EXT1 positivity compared with mixed class V LN in the confirmed LMN group (31.8% vs 68.2%, p=0.007). EXT1-positive patients in the confirmed and suspected LMN group showed significant differences in some clinicopathological data comparing with EXT1-negative patients (p<0.05). Follow-up data revealed that a greater proportion of patients in the EXT1-positive group achieved complete remission post-treatment (p<0.05). Cox regression analysis showed that EXT1 positivity was significantly correlated with complete remission across the entire study cohort (HR 5.647; 95% CI, 1.323 to 12.048; p=0.019). Kaplan-Meier analysis indicated that the EXT1-positive group had a higher rate of accumulated nephrotic remission compared with the EXT1-negative group in the whole study cohort (p=0.028).

Conclusions: The EXT1-positive group exhibited a higher active index and a more favourable renal outcome than the EXT1-negative group. It would be better to recognise suspected LMN with EXT1 positivity as a potential autoimmune disease and maintain close follow-up due to its similarities with confirmed LMN.

Keywords: Autoimmune Diseases; Lupus Erythematosus, Systemic; Lupus Nephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Relevance
  • Glomerulonephritis, Membranous* / diagnosis
  • Glomerulonephritis, Membranous* / drug therapy
  • Humans
  • Kidney / pathology
  • Lupus Erythematosus, Systemic*
  • Lupus Nephritis* / diagnosis
  • Lupus Nephritis* / pathology

Substances

  • exostosin-1