APOLIPOPROTIEN E IN C3 GLOMERULOPATHAY-A VALIDATION

Introduction:

 Apolipoprotein E (ApoE) is an amphipathic protein that plays an essential role in maintaining lipid homeostasis brought about by the regulation of lipoprotein trafficking as well as cholesterol absorption and excretion. A second major function of ApoE is renal extracellular matrix modulation since it regulates mesangial cell proliferation and matrix expansion Recently, Sethi et al demonstrated Apo E co-deposited in dense deposit disease. We had analysed Apolipoprotien E in biopsies with MPGN pattern due to different mechanism 

Methods:

All cases with membranoproliferative pattern(MPGN) pattern of glomerular injury over 5 years were analysed. Clinical details, immunofluorescence and electron microscopy were available. Biopsies were stained with Anti-ApolipoproteinE ( dilutions 1 : 10,000, positive control -canalicular aspect of hepatocytes showed 2+ intensity). 

Results:

There were 76 cases of immune complex mediated MPGN pattern(MPGN-IC), 13 of Dense deposit disease ( DDD), 12 of C3glomerulonephritis (C3GN),14 of class IV Lupus Nephritis(LN) and 8 IgA of nephropathy(IgAN). Normal kidneys (n-5)from autopsy were also stained. In normal glomeruli, apoliprotien E stained mesangium (1+ intensity). The luminal aspect of glomerular and peritubular capillaries stained with 2+ intensity. The basement membranes of glomeruli and tubules did not stain with apolipoprotien E. ApoE is normally expressed in the glomerular mesangium. The loss of staining or gain in intensity of staining of ApoE was noted. Gain of mesangial ApoE is seen in glomeruli of about 40% cases of DDD whereas only a quarter or less of other groups showed gain of ApoE. Loss of mesangial staining was seen most frequently in C3GN whereas a quarter of other groups also documented loss of Apo E staining Gain or loss of mesangial staining was statistically significant in DDD and C3GN as compared to the controls.  ApoE is normally absent in the glomerular basement membrane; any staining was noted as gain in staining. Glomerular basement membranes stained with ApoE in varying frequency in all the types of MPGN pattern but gain was frequent in DDD (58.33%) and least often in cases of C3GN ( 15.38%). Number of cases staining intensely is significantly more in DDD as compared to C3GN and normal biopsies Among the cases with sclerosed glomeruli all the cases of DDD (100%) showed positivity (3+ intensity) for ApoE whereas none of LN with sclerosed glomeruli were positive. A large proportion of C3GN ( 62.5%) also showed positivity (3+ intensity) for ApoE in the sclerosed glomeruli whereas lesser percentage was seen in IGAN and MPGN -IC (33.33 and 15.56% respectively). DDD and C3GN had significantly more ApoE stained sclerosed glomeruli as compared to other groups  

Conclusions:

ApoE expression was intense and constant in areas of mesangial expansion, basement membrane thickening, nodular lesions or glomeruloscleroses in DDD. Further intense staining with ApoE was recorded in sclerosed glomeruli especially in DDD and C3GN indicating accumulation of extracellular matrix which modified by presence of C3 is associated with increase in ApoE staining. This also correlated with increase of red refractile material seen in glomeruli of DDD and C3GN. Lesions with dominance of immunoglobulins(MPGN-IC, LN, IgAN) in deposits and not C3, expanded mesangial matrix/nodules did not stain with Apolipoprotien E

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.