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Lupus nephritis

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Lupus nephritis

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A 49-year-old woman comes to the office for management of her autoimmune disease. Her last urinalysis showed hematuria and casts. Laboratory testing showed elevated anti-DNA titers and low C3 and C4. A kidney biopsy is performed and shows subendothelial deposits on electron microscopy and wire loop appearance on light microscopy. Increase in which of the following is most likely involved in this patient's nephritis?

Transcript

The term ‘lupus’ refers to systemic lupus erythematosus, ‘nephritis’ refers to the ‘nephron,’ the Greek word for kidney, and ‘itis’ means inflammation, so lupus nephritis refers to inflammation of the kidney that results from having systemic lupus erythematosus.

Lupus is an autoimmune disease in which the immune system attacks various parts of the body, including the skin, joints, lungs, heart, central nervous system, and, of course, the kidneys.

In fact, about half of all individuals with lupus develop some form of lupus nephritis.

In lupus, what happens is that some cells have their DNA so badly damaged, that the cell undergoes programmed cell death, or apoptosis, and it dies. This produces all these little apoptotic bodies, and exposes the insides of the cell, including parts of the nucleus, like DNA, histones, and other proteins, to the rest of the body.

Now in lupus the immune system is more likely to think that cellular parts are foreign, or antigens, and since they’re from the nucleus, their referred to as nuclear antigens, and immune cells try to attack them.

Not only that though, individuals with lupus have less effective clearance, essentially they aren’t as good at getting rid of the apoptotic bodies and so they end up having more nuclear antigens floating around.

So as a result of all of this, B cells start producing antibodies against these pieces of nucleus, which are called antinuclear antibodies.

These antinuclear antibodies bind to nuclear antigens, forming antigen-antibody complexes, which drift away in the blood and deposit in various places including the kidneys.

These immune complexes can then initiate an inflammatory reaction, which is known as a type III hypersensitivity reaction.

Lupus nephritis is classified into various types depending on the exact site of these immune complexes and subsequent inflammatory reaction. The most common site of deposition is just underneath the capillary wall, also known as the endothelium, but deposits can also be within the Bowman’s space of the nephron, the basement membrane, or near the mesangial cells.

The extent of inflammation within the kidney can be focal, involving nephrons in just one area, or diffuse, involving almost all of the nephrons in both kidneys.

In the majority of cases lupus nephritis presents as a nephrotic syndrome, which means that the damage to the nephron allows plasma proteins to get into the urine, which causes proteinuria—typically greater than 3.5 grams per day.