J Rheum Dis  
Interstitial Inflammation in the ISN/RPS 2018 Classification of Lupus Nephritis Predicts Renal Outcomes and is Associated With Bcl-2 Expression
Sang Jin Lee, M.D.1, Eon Jeong Nam, M.D., Ph.D.1, Man Hoon Han, M.D.2, Yong Jin Kim, M.D., Ph.D.2
1Division of Rheumatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, 2Department of Pathology, School of Medicine, Kyungpook National University, Daegu, Korea
Correspondence to: Yong Jin Kim, http://orcid.org/0000-0002-9867-0752
Department of Pathology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. E-mail: yyjjkim1@gmail.com
Received: March 8, 2022; Revised: May 30, 2022; Accepted: June 28, 2022; Published online: July 26, 2022.
© Korean College of Rheumatology.

This is a open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: To investigate the histopathological characteristics of patients with lupus nephritis in the 2018 revised International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification and assess the prognostic factors.
Methods: This study enrolled 92 patients with lupus nephritis, who had conventional treatment and renal biopsy. Each renal tissue was evaluated according to 2018 ISN/RPS classification, and quantified apoptotic regulator protein, the B-cell lymphoma-2 protein (Bcl-2), expressions in selected lymphocyte subsets were measured using novel computational approaches using multicolor confocal images. Histopathological characteristics and prognostic factors of end-stage renal disease (ESRD) and chronic kidney disease (CKD) were compared. Follow-up data were obtained, and survival analysis was conducted.
Results: During follow-up period (average: 74.3 months), 16 and 18 patients progressed ESRD and CKD, respectively. Multivariable analysis of age, sex, disease activity and pathological features in ISN/RPS demonstrated the extent of interstitial inflammation (grade 0~3) was significantly associated with both ESRD and CKD. When interstitial inflammation was divided into mild (grade 0, 1) and severe (grade 2, 3), Cox regression analysis showed that patients with severe interstitial inflammation were significantly increased risk of both ESRD and CKD (hazard ratio: 4.67 and 3.8, respectively). Bcl-2 expression in CD4+ and CD20 cells was significantly higher in the severe interstitial inflammation group compared to in mild interstitial inflammation patients (p=0.006 and 0.010, respectively).
Conclusion: The extent of interstitial inflammation can predict clinical renal outcomes. Significantly elevated Bcl-2 expression in both CD4+ and CD20 cells was found in severe interstitial inflammation compared with mild interstitial inflammation.
Keywords: Lupus nephritis, Inflammation, Prognosis


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