complement in PSGN

[kinzy]

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Hi everyone! I'm new to SDN and looking for some clarification on a concept because I think I am missing something in my understanding...in any complement-fixing disease (ie, PSGN, SLE, etc) you use up complement ---> leads to low C3 levels. So my question is, how come we can see C3 by immunofluoresence in PSGN (in the mesangium/GBM) and some of the other nephritic syndromes? Wouldn't the C3 be be used up during the inflammatory process? If so, how come we can still visualize it on immunefluoresence?

 

[GadRads]

Liver is probably making more complement proteins i.e. more C3.

 

[periaqueductal]

Immunofluorescence is looking at the actual glomueruli, where you will see the C3 that has deposited. Because you're taking complement out of the blood and depositing it on the Glomerular basement membrane/mesangium you are decreasing circulating levels. So when you run blood tests it decreases levels of C3. But you will see it when you immunofluoresce the tissue.

 

[kinzy]

Immunofluorescence is looking at the actual glomueruli, where you will see the C3 that has deposited. Because you're taking complement out of the blood and depositing it on the Glomerular basement membrane/mesangium you are decreasing circulating levels. So when you run blood tests it decreases levels of C3. But you will see it when you immunofluoresce the tissue.

Thanks periaqueductal! As a follow up question...I think I'm a little confused because c3 in the synovial fluid is low in RA due to it being used up in the inflammatory process - so does this same concept of using up complement at the site of inflammation (when the c3 deposits in the kidney in PSGN) not apply? I understand the concept of low serum c3 but am just not understanding how in RA, synovial fluid can have low complement at the site of inflammation while in PSGN, we see complement (instead of seeing low complement) at the site of inflammation.

Any thoughts on this?

 

[GadRads]

In normal kidney, you shouldn't see any C3. If any, it should be neglibible and be of no significance. PSGN is an inflammatory process which will upregulate synthesis of factors necessary for such inflammation. While the liver makes complement to feed the inflammatory process, the neutrophils in the kidney deplete them as fast as they are receiving such, leading to low serum complement.

 

[periaqueductal]

Thanks periaqueductal! As a follow up question...I think I'm a little confused because c3 in the synovial fluid is low in RA due to it being used up in the inflammatory process - so does this same concept of using up complement at the site of inflammation (when the c3 deposits in the kidney in PSGN) not apply? I understand the concept of low serum c3 but am just not understanding how in RA, synovial fluid can have low complement at the site of inflammation while in PSGN, we see complement (instead of seeing low complement) at the site of inflammation.

Any thoughts on this?

I'm not sure I completely understand your reasoning/question, but here's my answer to what I think you're saying.
It is the same concept in PSGN and RA. Think about it in terms of hypersensitivity reactions:
Both PSGN and RA are type III hypersensitivity reactions (HPS)- (RA is also type IV but not for this example)
When you have type III HPS you get complexes of Ab-Ag which activate complement. This complement binds the complex and deposits in the tissue cause the tissue damage.
Let's imagine that normally you have 100 molecules of C3 circulating at all times (this includes in synovium). You get RA and your Ab-Ag complexes activate 70 of those to C3a which binds to the IgG molecules in the complex and bind to the tissue effectively removing it from circulation.
You are left with 30 molecules of C3a left to spread between your blood and synovial fluid. So when you draw to assess for levels it will be low. The exact same concept occurs in PSGN. Hope this helps.

 

[thehundredthone]

Thanks periaqueductal! As a follow up question...I think I'm a little confused because c3 in the synovial fluid is low in RA due to it being used up in the inflammatory process - so does this same concept of using up complement at the site of inflammation (when the c3 deposits in the kidney in PSGN) not apply? I understand the concept of low serum c3 but am just not understanding how in RA, synovial fluid can have low complement at the site of inflammation while in PSGN, we see complement (instead of seeing low complement) at the site of inflammation.

Any thoughts on this?

The site of inflammation in RA is the joint cartilage and bone, not the synovial fluid. That's where you'll find the C3 if you looked for it in the joint. Same as in the kidneys, where it's the GBM and mesangium that has C3 deposits, and not the tubular filtrate.