Evaluation of the expression of Beclin-1 and LC3 in lupus nephritis

Abstract

SLE is a complex and common autoimmune disease, presenting with lupus nephritis (LN) in 30-60% of patients. Macroautophagy, a mechanism for the degradation of intracellular contents, is deregulated in numerous metabolic, neurodegenerative, cancer and autoimmune diseases. Although autophagy has been shown to be involved in the pathogenesis of SLE, the extent to which it is present in target organs remains uncertain. Our aim was analyze and describe the presence of macroautophagy in the various renal compartments in different classes of LN in a cohort of human renal biopsies.

The design was retrospective, observational, cross-sectional and correlational in renal biopsies from adult lupus patients of both sexes. The sample number: 35. The methodology used was immunohistochemistry for Beclin-1 and LC3 and the number of immunopositive cells was analyzed at the level of renal tubules using H-Score (semi-quantitative evaluation). The variables analyzed were: distribution by biological sex, age, proteinuria, hematuria, creatininemia, LN class, Beclin-1 and LC3. Fisher's exact test was performed for qualitative variables and T-test for difference in means for quantitative variables, as well as binary logistic regression. Significance level of 0.95 and 0.90, as appropriate.

In both proliferative and nonproliferative LNs, both molecules were expressed in the tubular epithelial lining. LC3 was identified in podocytes of proliferative classes. Immunodetermination of Beclin-1 and LC3 demonstrated a statistically significant relationship between the proliferative classes of LN and Beclin-1 labeling (p=0.0314, 95% CI), while for LC3, although there was a statistically significant relationship, it was with a lower confidence interval (p=0.0936, 90% CI). No statistically significant associations were observed between clinical variables and the expression of the macroautophagy marker molecules analyzed (LC3 and Beclin-1).

In conclusion, macroautophagy is a cellular and molecular mechanism preferentially activated in proliferative LNs, both at the tubular and glomerular levels, so its role described as multifaceted could be, not only class-specific, but also cell type-specific, and thus become a therapeutic target in the future.