C3 and C4 complement levels in MCAD?

[Tomas]

Hi!
Docs are trying to decide if my issue is MCAD or some connective tissue disease (or something else...) and say that C3 and C4 should be low in the latter and probably normal in MCAD, but they don't seem sure.
My C3 and C4 are exactly between normal and low now, they used to be normal but on the lower side.
My other rheumo test are OK, so I don't know what to think. What are your complement levels if you're suffering from MCAD?

I described my weird case here http://forums.phoenixrising.me/inde...ly-symptom-spring-summer-exacerbations.42599/

 

[JaimeS]

Complement levels certainly vary a great deal among the people here. You'll get super-high, super-low and normal values when you ask around.

I entered mcad, c3 and c4 into pubmed and only got this. I'm afraid that means there may not be definite information available.

 

[Tomas]

Thanks for the answer! It looks like complement levels won't be a clue for my diagnosis.

 

[TrixieStix]

Hi!
Docs are trying to decide if my issue is MCAD or some connective tissue disease (or something else...) and say that C3 and C4 should be low in the latter and probably normal in MCAD, but they don't seem sure.
My C3 and C4 are exactly between normal and low now, they used to be normal but on the lower side.
My other rheumo test are OK, so I don't know what to think. What are your complement levels if you're suffering from MCAD?

I described my weird case here http://forums.phoenixrising.me/inde...ly-symptom-spring-summer-exacerbations.42599/

I just found out tonight that my C3 and C4 and very low. Trying to figure out what it could mean. I keep finding references to those being low in people with Lupus, but my ANA has always been normal.

NOTE: This info is only referring to Complement C3 and C4 and NOT to C3a and C4a which are different things.

 

[TrixieStix]

@JaimeS @Tomas

I found this when I searched about low C3 and C4 related to connective tissue disease...

"Serum levels of complement components can serve as markers of disease activity. In immune complex deposition disease, serum complement proteins are consumed and serum levels decrease. Immune complex disease results from the deposition of antigen-antibody complexes in involved organ tissues. In immune complex glomerulonephritis in SLE, decreased C3 and C4 indicate increased consumption and indicate disease activity. In contrast, increases of C3 and C4 indicate inflammatory disorders as these proteins are also acute phase reactants. Hypocomplementemia is generally not specific for any disease and may be secondary to nonrheumatic diseases such as subacute bacterial endocarditis or poststreptococal glomerulonephritis. If C4 is low compared to C3, it may indicate the presence of cryoglobulins or the genotype C4 null allele. If CH50 is low or undetectable, it may indicate a deficiency of one or more complement components. Genetic/congenital deficiencies of early complement components (C1 to C4) may increase the risk for development of immune-complex diseases. For example, congenital C1q deficiency, although rare in the general population, is associated with individuals who develop lupus."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832720/

NOTE: This info is only referring to Complement C3 and C4 and NOT to C3a and C4a which are different things.

 

[TrixieStix]

and this has good info too...

"C3 alone is often decreased in infectious disease (septicaemia, endocarditis), C3 and C4 are often both decreased in immune complex disease, C4 alone is characteristically decreased in angioedema, immune complex diseases particularly vasculitis and in cryoglobulinaemia and cold agglutinin disease.
Measurement of serum complement is useful in the monitoring of specific immune complex diseases e.g SLE and infectious diseases post streptococcal disease, subacute bacterial endocarditis. Consumption of one or both components may also be useful prognostically e.g nephritis in lupus.

Though genetic deficiencies of C3 are exceedingly rare, deficiencies in other components which are more common (though still very rare) can result in low C3. Genetic deficiencies in C4 are rarely detected. C1 inhibitor deficiencies are often detected by investigation of unexpected low C4 levels."

https://www.southtees.nhs.uk/services/pathology/tests/complement-c3-c4/

NOTE: This info is only referring to Complement C3 and C4 and NOT to C3a and C4a which are not the same thing.

 

[Gingergrrl]

I just found out tonight that my C3 and C4 and very low. Trying to figure out what it could mean. I keep finding references to those being low in people with Lupus, but my ANA has always been normal.

@TrixieStix I hope to ask you some questions (later) and learn more about compliment level testing/results and what they mean in relation to autoimmune disease and MCAS. I have never been tested for compliment levels (to the best of my knowledge) but assume my levels are low like yours.

 

[JaimeS]

@TrixieStix -- awesome work! I didn't find that degree of info in my searches. There is more info on C3 and C4 here:

http://forums.phoenixrising.me/index.php?threads/c3a-c4a-test-lyme-vs-mold.31215

 

[TrixieStix]

@TrixieStix -- awesome work! I didn't find that degree of info in my searches. There is more info on C3 and C4 here:

http://forums.phoenixrising.me/index.php?threads/c3a-c4a-test-lyme-vs-mold.31215

They aren't talking about the same thing in that thread that I am talking about. Component tests for C3 and C4 are not the same thing as tests for C3a and C4a.

Unfortunately I am seeing a lot of confusion in online threads about Lyme where people are mixing up C3/C4 and C3a/C4a and giving bad information and/or confusing people further. Someone will ask what their C3 or C4 test results mean and they will get responses incorrectly assuming they are referring to C3a and C4a tests.

This is the 3 tests I had done... http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=284&labCode=QAW

C3a testing... http://www.questdiagnostics.com/testcenter/TestDetail.action?ntc=17689

this is only test I could find via Quest for C4a... http://www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=19956&labCode=DLO&labName=OK - Oklahoma City 225 NE 97th Street (800)891-2917 (DLO)

 

[antherder]

This article gives an overview of the complement system. Apologies if it has already been posted;

http://primaryimmune.org/about-prim...ecific-disease-types/complement-deficiencies/

 

[TrixieStix]

@JaimeS @Gingergrrl

I've learned that Complement C3a, C4a, and also C5a (these are NOT what I had tested) are Anaphylatoxins aka: "complement peptides" that are produced as part of the activation of the complement system.

"Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defense. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments. A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability. They also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals..."

https://en.wikipedia.org/wiki/Anaphylatoxin

I also found this article.

"Patients often ask if there are other medical conditions that may lower or raise the C3a and/or C4a. Both of these complement products may be increased in normal pregnancy and in certain types of vasculitis (an inflammatory condition that destroys blood vessels). C4a levels are elevated in adult insulin dependent diabetes. Those who suspect that chronic fatigue syndrome (CFS) may actually be misdiagnosed Lyme disease may not be surprised to hear that C4a is also elevated in CFS patients. In fact the C4a is probably elevated in all sorts of infections, and therefore is not specific to Lyme. "

http://www.publichealthalert.org/ro...plement-proteins-in-chronic-lyme-disease.html

 

[Gingergrrl]

@TrixieStix In 2015 when I saw a mold specialist (MD) she wanted me to do blood tests for C3 and C4 but IIRC, I never did the final set of tests (which included these) b/c it was so much testing and we were trying to move at that time, etc.

I need to go back and look at my lab slips b/c I'm not sure if what my former mold doc wanted me to test is the same as these autoimmune tests. I think they have similar names but are two different things. So... I am not much help yet to this conversation LOL

 

[TrixieStix]

@TrixieStix In 2015 when I saw a mold specialist (MD) she wanted me to do blood tests for C3 and C4 but IIRC, I never did the final set of tests (which included these) b/c it was so much testing and we were trying to move at that time, etc.

I need to go back and look at my lab slips b/c I'm not sure if what my former mold doc wanted me to test is the same as these autoimmune tests. I think they have similar names but are two different things. So... I am not much help yet to this conversation LOL

I bet she was talking about C3a and C4a testing rather than C3 and C4.

 

[Gingergrrl]

I bet she was talking about C3a and C4a testing rather than C3 and C4.

I think you are right and my former mold doc wanted C3a and C4a.

 

[TrixieStix]

I found this detailed medical journal article outlining how LOW Complement levels (Hypocomplementemia) relate to various specific diseases, conditions, etc. It's full of great information!

http://www.kidney-international.org/article/S0085-2538(15)57192-5/pdf

 

[TrixieStix]

Description of the Complement System and Its Pathways

The complement system consists of more than 30 proteins, present in blood and tissues, as well as other proteins anchored on the surfaces of cells. The primary functions of the complement system are to protect from infection, to remove particulate substances, (like damaged or dying cells, microbes or immune complexes) and to help modulate adaptive immune responses. As part of the innate immune system, complement acts immediately to start the process of removal and resolution of the problem. Complement works with the inflammatory cells of the innate immune system and those of adaptive or acquired immunity. It also interacts with proteins of the coagulation and kinin generating systems along with others.

Complement activation is tightly regulated and designed to kill invading microbes while producing minimal “collateral damage” that could result in the destruction of host tissues. Complement proteins in the circulation are not activated until triggered by an encounter with a bacterial cell, a virus, an immune complex, damaged tissue or other substance not usually present in the body.

Complement activation is a cascading event like the falling of a row of dominoes. It must follow a specific order if the end result is to be achieved. The circulating proteins have been grouped into three activation pathways, based on the types of substances and proteins that initiate the activation. If you visualize a trident, the three tines represent the different initiation routes, while the handle represents the lytic mechanism by which this cascade ultimately destroys the threat, no matter which activation pathway started the response.

http://primaryimmune.org/about-prim...ecific-disease-types/complement-deficiencies/

 

[TrixieStix]

And lastly....

"In addition to their role in innate immunity against invading pathogens, complement proteins can also modulate diverse developmental processes, such as cell survival, growth, and differentiation in various tissues, and in tissue or organ regeneration. A critical role for the classical pathway in synaptic remodeling in mice was recently identified.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952982/

 

[TrixieStix]

I think you are right and my former mold doc wanted C3a and C4a.

I had my first ever appointment with an allergist/immunologist (knowledgeable in immune deficiencies etc) yesterday @ University of Washington in Seattle. I am seeing him to figure out why my Complement C3 is so low (only 30% of normal).

Funny enough he asked me if I have ever heard of "Mast Cell Activation Disorder" and told me he thinks it's a possible explanation for my symptoms. He is running bloof tests for
it. And also running tests to make sure my low C3 isn't due to a genetic deficiency (rare) in the complement system.


The test results will take a few weeks to get back. I really hope we find some answers because ME/CFS does not explain everything going on with me.

 

[Gingergrrl]

I had my first ever appointment with an allergist/immunologist (knowledgeable in immune deficiencies etc) yesterday @ University of Washington in Seattle. I am seeing him to figure out why my Complement C3 is so low (only 30% of normal).

It's good to hear an update @TrixieStix and am glad you got to see that doctor.

Funny enough he asked me if I have ever heard of "Mast Cell Activation Disorder" and told me he thinks it's a possible explanation for my symptoms. He is running bloof tests for
it. And also running tests to make sure my low C3 isn't due to a genetic deficiency (rare) in the complement system.

That is great and I am glad you found someone who is knowledgeable about MCAS. Did he think there was a connection between your low C3 and MCAS or these were two separate things?

I really hope we find some answers because ME/CFS does not explain everything going on with me.

Please keep us posted and I felt the same way (that ME/CFS did not explain what was going on with me, even though on many points, I match with it).

 

[antherder]

@TrixieStix,

Glad to hear you are making progress. Sorry if I've got this wrong, but I think you mentioned kidney disease in your family? You've probably seen this already, but in case you haven't, it mentions reoccurring bacterial infections, and renal failure;

Complement Factor H Deficiency

https://www.omim.org/entry/609814

I stumbled across it when using this search;

http://www.findzebra.com/raredisease?q="Low c4"#accordion-body-17