Convenient Evaluation of Magnitude of Glomerulonephritis in BXSB/Mp Lupus Mice

Objective: Kidney involvement is one of the most important clinical features of systemic lupus erythematosus (SLE). Therefore, histopathological analysis of renal sections is necessary to evaluate the magnitude of lupus-like diseases. However, histopathological grading requires advanced pathological skills, otherwise the subjective views of the investigator can enter into evaluation. Here we show that in the case of a BXSB lupus mouse strain, the area and the long axis of glomeruli can be used as an objective index that can aid in the evaluation of the severity of lupus glomerulonephritis. Methods: Previously, we investigated the effects of treatment that involved the induction of bone marrow chimerism to BXSB lupus mice. Based on the results of histopathological analysis and immunofluorescence staining, the progression grades of lupus glomerulonephritis of seven experimental groups were decided. Then, we reevaluated the histopathological grade and the other elements of glomeruli in each experimental group. For the second examination, more than 30 glomeruli newly assessed on each section, and more than five sections from each group were analyzed. The area, long axis and short axis of all captured glomeruli were measured. The relationships between the histopathological score evaluated by two different pathologists, or between the mean histopathological scores and mean area and mean long/short axes of the glomeruli were analyzed using multiple linear regression. Results: There was a direct correlation between two scores that were reported by two different pathologists. Glomeruli with severe inflammatory exudates were found to be easy to grade correctly, while it was more difficult to differentiate thickening of mesangial cells. In contrast, the mean area and the mean axis of glomeruli had a high correlation to histopthological grade even in the low-grade stages of the disease, when minimal thickening or proliferative mesangial changes have occurred. Conclusion: The size of glomeruli correlates with the histopathlogical grade, especially the long axis of glomeruli, which is the easiest direction to measure. We thus conclude that this parameter can serve an auxiliary index of the severity of lupus glomerulonephritis in the BXSB lupus mouse strain.