[CIS PIDD] Low CH50

[Seppänen Mikko]

Dear Santosh, 
Previous replies have covered most aspects, 
A) C4B def, even total ( both C4B alleles missing, 8% of Finns, one of the highest in the world) would not cause, at least in our lab and in properly handled sample, CH50 as low as 15. That suggests either that the shipment/ sample storage has failed or that there is vigorous complement consumption as well. 

If both C4A:s missing,  occasionally seen this low levels, probably because there is concurrent consumption as well ( lupus, lupus like). Could be seen in HUVS and other states with C1q-autoantibodies, then AH50 and CH50L/LH50 activities very low as well. Usually not a total CP def,  like previously commented. In B cell malignancies (CLL, MM, lymphomas, others) low not zero CH50 seen as well. 

In periodic fevers (her presenting symptom) not really seen, and recurrent "viral infections" most likely not recurrent intraoral HSV1 (in which HLA homozygosity and total C4B or C4A defs seen together)? 

A lupus about to manifest? 
B more likely false sample storage and nothing to do with her disease, which in itself could be PFAPA (not all have aphthous stomatitis in it, especially if of North European origin) , HIDS/MKD, TRAPS, cyclic neutropenia or like? 

Thus, measure all 3 pathways with meticulous handling of sample, 
if one or more low but not zero (only LH50 zero not very helpful, seen in MBL2/MASP2def), try mesuring consumption and C1qAbs or C1inh (activity and level) if clinically indicated, likewise look for B cell malignancy, C4 genotyping indicated if lupus like disease? 

... but if normal AH50 and CH50 after all, focus on finding out if PFAPA or autoinflammatory syndrome. 

Yours
Mikko Seppänen, Helsinki Finland
________________________________________
Lähettäjä: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] käyttäjän Santhosh Kumar/FS/VCU [skumar at vcu.edu] puolesta
Lähetetty: 11. heinäkuuta 2012 16:58
Vastaanottaja: pagid at list.clinimmsoc.org
Aihe: [CIS PIDD] Low CH50

Dear All,

I have 6 y/o F who was referred to me by my ID colleague for recurrent febrile episodes since starting school. She has not had any major infections which needed hospitalization. Most of her febrile episodes were thought to be virally related. Her immune work up is normal except for low CH50 levels (repeated x 2- 12 and 15U/ml). His other classic pathway complements are normal (c2, c3, c4, c6, c7, c8,c9). AH50 is pending. I had heard of falsely low CH50 levels in past depending on the assay used. My question is:

Is this a false low CH50 level and if so is there a  better assay which can be used to confirm


Thank you,

Santhosh Kumar, MD
Assistant Professor,
Allergy & Immunology
Medical college of Virginia
Ph-  804-628-1605
Fax-804-828-1751