The Cullen Endowed Professor of Biomedical Engineering, Chandra Mohan, Hugh Roy, and Lillie Cranz, is reporting the first use of the powerful imaging mass cytometry (IMC) to examine the kidneys of patients with lupus (systemic lupus erythematosus), an autoimmune disease that can affect multiple organs and become fatal, and to diagnose lupus nephritis (LN) in those patients.
LN is a severe kidney inflammation that is a leading cause of mortality in lupus patients. Up to 60% of SLE patients develop renal symptoms, with 5-20% developing to end-stage kidney disease within ten years.
IMC can detect the presence of up to 37 different proteins in human tissue at the same time, which is a considerable advancement over the old technique, which could only detect 1-3 separate proteins inside a single tissue. IMC has been used to define the cellular composition of the human kidney, discriminate between cell types, and find novel disease indicators. It is frequently used in conjunction with machine learning methods.
“We postulated imaging mass cytometry may shed novel insights on the molecular makeup of proliferative lupus nephritis due to unique advantages that allow high-dimensional tissue profiling,” Mohan writes in Clinical Immunology. “This research looks at the expression profiles of 50 target proteins in lupus nephritis and healthy kidneys.”
The current gold standard for LN diagnosis is a painful kidney biopsy and examination of the tissues removed to evaluate disease prognosis and treatment response.
“However, there is low inter-pathologist concordance when determining classes and pathology indices, which can lead to misclassification of LN, improper disease treatment, and sub-optimal patient outcomes,” Mohan explained. “Renal biopsies also provide a limited amount of tissue, restricting the type and extent of analysis that can be performed on a sample.”
IMC has numerous significant benefits, including the ability to target tissue regions for subsequent investigation. Mohan discovered both decreased and elevated disease indicators that signal to renal illness during the IMC investigation and evaluation of 21 patients, as well as that a subgroup of glomeruli (the microscopic network of blood arteries that serve as cleaners of the kidney) may be enlarged in some LN patients.
“In kidney biopsies from patients with renal diseases, including LN, decreased expression of epithelial markers and increased expression of mesenchymal markers, also known as epithelial to mesenchymal plasticity (EMP),” stated Mohan. “It is very likely that the parietal epithelial cells encircling the glomeruli are another site of EMP in proliferative LN, but this needs to be confirmed using additional markers.” EMP might likely damage other cells in the LN kidneys, but this has to be further researched.”
Crosslee Titus, a postdoctoral scholar at UH, collaborated on the research alongside Mohan’s team. Teams led by Shu-Hsia Chen, Houston Methodist Research Institute; Minghui Zhao, Peking University First Hospital, Beijing, PR China; and Anthony Chang, The University of Chicago are also engaged in the research.