In another surprise that challenges the conventional approach to lupus nephritis, Dr. Fava and colleagues have discovered that granulocytes are abundant in the kidneys of patients with lupus nephritis, including in pure membranous disease (i.e., class V lupus nephritis in the ISN/RPS classification system). However, he cautioned attendees not to be fooled by the absence of these cells on the average renal biopsy. Unlike typical neutrophils, those cells seen in patients with lupus nephritis are mostly unilobate and may be missed by traditional histology because they appear to localize most to the tubulointerstitium and may also appear within areas of fibrosis.
In Sum
The lectures provided by all three speakers were captivating to an audience willing think beyond B cells. (Note: As an aside, Dr. Fava’s recent New England Journal of Medicine editorial titled, “To B or Not to B—the Role of B-Cell Depletion in Lupus Nephritis” is a must-read on this broader topic).6
For a disease as complex as lupus, it is important to consider the many parts of the immune system that may play a role.
Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.
References
- Zeidi M, Kim HJ, Werth VP. Increased myeloid dendritic cells and TNF-α expression predicts poor response to hydroxychloroquine in cutaneous lupus erythematosus. J Invest Dermatol. 2019 Feb;139(2):324–332.
- Skopelja-Gardner S, Tai J, Sun X, et al. Acute skin exposure to ultraviolet light triggers neutrophil-mediated kidney inflammation. Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):e2019097118.
- Caielli S, Cardenas J, de Jesus AA, et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell. 2021 Aug 19;184(17):4464–4479.e19.
- Parikh SV, Almaani S, Brodsky S, et al. Update on lupus nephritis: Core curriculum 2020. Am J Kidney Dis. 2020 Aug;76(2):265–281.
- Fava A, Buyon J, Magder L, et al. Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis. JCI Insight. 2024 Jan 23;9(2):e172569.
- Fava A. To B or not to B—the role of B-cell depletion in lupus nephritis. N Engl J Med. 2025 Apr 17;392(15):1545–1547.
