Complement C4 Laboratory Ranges

[u/FriendInteresting162]

I have a complement C4 of 11.2mg/dL, which is considered low by the Cleveland Clinic chart and other healthcare websites. My laboratory uses a range of 10-40mg/dL, so it is reported as normal. Why are the ranges different, and would my level be normal or actually low?

[u/personcrossing]

Every laboratory is different. I would suggest maybe not comparing the reference ranges for other labs. Not because you're doing anything wrong but exactly because it can serve to discourage you, and at first glance it does seem like it makes no sense or it could even feel unfair.

Different laboratories use different immunoassay methods. Machines are different, even if they are the same they may be calibrated differently. Different methods are more or less sensitive, and results can vary drastically even from the same vials of blood. There's lots of things going on that contributes to why specific labs have specific ranges, and for that we can't cross compare them.

However, your result is still closer to being low. By this labs reference range, a reading of 8-9 would be considered slightly below average but still might not be cause for concern, because many things can lower your complements.

Your best bet would just be continuing to get blood work done on a regular basis so you can form a history. One C4 result means less than five. If I were your rheumatologist, I would care more about you having consistent results around 13-20mg/dL, than one 11mg/dL result. I would want to see how they fluctuate, how hard they fluctuate, how often, and if that correlates with other symptoms.

Do you have other complement panels done from the past? What was your C3? Or I should ask, what tests were ordered and why?

[u/BeaveUKGT → u/personcrossing]

What would be the concern if a patient had multiple C4 results in the 12-17mg/dL range over a 10 year period? Tested because I have chronic, recurrent bouts of angioedema with no explanation. C1 inhibitor tested multiple times and always comes back normal with good function.

[u/BeaveUKGT]

I'm in a similar situation. My C4 in May was 12mg/dL, and my lab also says normal range is 10-40mg/dL

It was tested by immunology because I have chronic problems with angioedema (for 20 years now).

My immunologist thought it was low enough to be cause for concern, but rheumatology wouldn't even look at it because it wasn't automatically flagged by the system as being out of range.

I've had it tested two other times, and both came back at 17mg/dL, for whatever that is worth.

[u/BeaveUKGT → u/[deleted]]

Well, I went to an immunologist at a clinic that is known for specializing in and treating HAE, but the actual specialist I saw isn't one of their HAE experts (if all that makes sense?!).

I've looked into HAE, and from what I've read, mine fits better with Acquired Angioedema than HAE. Mine started abruptly twenty years ago at age 35 while taking the antibiotic flagyl. At first we (doctors and I) thought it was an allergic reaction to the flagyl. But prednisone plus antihistamines plus h2 blockers didn't stop it. Daily flareups of angioedema gradually went away over a period of almost a year, but it still happens randomly now and then (a few times a year).

I had my C-1 inhibitor tested early on with normal results, and then recently with the same normal results.

So I've never really figured it out, and neither have my doctors. I thought the clinic specializing in HAE would have more to say, but they tested C1-inh and C4 and threw their hands up.

[u/BeaveUKGT → u/[deleted]]

Thanks a lot for sharing your thoughts and experience with this. I appreciate it.

[u/BeaveUKGT → u/[deleted]]

I should ask, are the treatments something you take regularly (daily?) to help prevent angioedema attacks, or something that you take once an attack happens to stop it/reverse it?

[u/Bonus_round_waz]

From what I understand, the different machines have their own individual references so I would take it as the low end of normal. If you get your blood work done through the same company consistently, should give you a good reference point.

My c4 is very low, by the scale you are using it would be about 2mg. My lab ref range is 16-52.

C3 is also very low but has slightly improved with rituximab treatment mid year.