[CIS-PAGID] low ch50 with normal complement levels?

[Patsy Giclas]

Dear Ashish,

The Low or absent CH50 activity in both twins suggests a hereditary
deficiency.  I agree with the other responders that it is likely to be C2,
but wouldn't say for sure without the evidence that the rest of the
components are functionally normal.  The AH50 is important to test the
components from C3 through C9, as suggested by Dr Gewurz. If the AH50 is
normal, then I would recommend testing C1, C2 and C4 functions. C2
deficiency often presents in young children with recurrent URIs so it fits
the phenotype described here.  There are two forms:  type I C2 deficiency
(90% of patients) is due to a 28-base-pair deletion in the gene, that
results in no C2 protein being produced.  Type II C2 deficiency can be due
to any of several single nucleotide polymorphisms as well as frame shift or
other mutations that have variable effects including nearly normal protein
levels but no function.  We have seen one case at National Jewish in which
the patient was a double heterozygote for 2 different Type II defects, one
from each parent, and was thus functionally deficient in C2.

You didn't give the actual values for the components that were tested that
you said were normal, but another possibility, if C2 is normal, is a C8
deficiency. If the level of C8 was below the normal mean value the protein
could be missing one of the three chains that make it up and would not have
any hemolytic activity.

I'll be happy to answer any other questions.

Patsy Giclas

Patricia C. Giclas. Ph.D.
Director, Complement Laboratory
Advanced Diagnostic Laboratories
Professor, Pediatrics Dept,  Allergy and Immunology Division
National Jewish Health
1400 Jackson St., Denver, CO 80206 U.S.A.

Office: D409, Neustadt Building
Phone: 303-398-1217
Fax: 303-270-2128
Email: giclasp at njhealth.org



> From: Anita Gewurz <agewurz at rush.edu>

> Reply-To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

> Date: Mon, 15 Nov 2010 19:25:55 -0700

> To: "pagid at list.clinimmsoc.org" <pagid at list.clinimmsoc.org>

> Cc: Ashish Kumar <Ashish.Kumar at cchmc.org>

> Subject: Re: [CIS-PAGID] low ch50 with normal complement levels?

> 

> Dear Ashish,

> 

> Like Drs. Vasconceles and Gonzalez, I suspect the problem is

> homozygous C2 deficiency and would also check the AH50.

> 

> Undetectable CH50 levels can certainly result from complement

> activation, as suggested by Dr. Verbsky, but in the situation you

> describe a congenital C defect is most likely.  Homozygous deficiency

> of an early-acting classical or mannose-binding lectin pathway

> component may present in infancy with infection or lupus-like

> disease.  Normal alternative pathway hemolytic activity (AH50)

> excludes deficiency of C3, C5, C6, C7, C8 or C9.

> 

> Patricia Giclas PhD, Director of the Complement Laboratory at National

> Jewish can help 

> http://www.nationaljewish.org/research/diagnostics/adx/labs/complement.aspx

>   .

> 

> Sincerely,

> 

> Anita Gewurz MD

> Section of Allergy and Immunology

> Department of Immunology/Microbiology

> Rush Medical College

> Chicago IL 60612

> 

> 

> On Nov 15, 2010, at 7:11 PM, <dmvascon at usp.br> wrote:

> 

>> Dear Ashish

>> 

>> I would suggest to test for APH50, in order to evaluate alternate

>> pathway function. The combination of both functional screening tests

>> (CH50 and APH50) is very useful to drive the evaluation of

>> complement defects:

>> 

>> CH50 indetectable, APH50 normal: defects of classical pathway

>> activation

>> CH50 normal, APH50 indetectable: defects of alternate pathway

>> activation

>> CH50 and APH50 indetectable: defects of membrane attack complex.

>> 

>> These functional tests are fundamental, due to the fact that in a

>> qualitative defect of any component of complement (without

>> quantitative defect), there will be a reduction of the value of the

>> screening test, without reduction of the quantitation of any

>> component by any immunochemical method (nephelometry, turbidimetry

>> etc.).

>> 

>> Usually complement deficiencies present clinical manifestations

>> later in life (usually autoimmunity in classical pathway activation

>> components - C1, C4, C2) and infections by encapsulated bacteria -

>> mainly Neisserial infections - with alternate pathway or membrane

>> attack complex component deficiencies.

>> 

>> Therefore it is important to test for other possible complement

>> defects and follow-up these patients closely to detect any possible

>> clinical and immunological manifestation as early as possible.

>> 

>> Best regards,

>> 

>> Dewton

>> 

>> 

>> Citando Ashish Kumar <Ashish.Kumar at cchmc.org>:

>> 

>>> Dear Friends,

>>> 

>>> I recently saw a set of twin girls who were born at 32 weeks with

>>> twin-twin transfusion syndrome; the smaller of the two has needed a

>>> couple hospitalizations with URIs due to hypoxia. She has chronic

>>> rhinorrhea, a history of wheezing that responds to bronchodilator

>>> therapy. Someone checked her ch50 and it was <10; recheck showed

>>> the same. Her twin was then checked and hers too was <10. Their

>>> complement levels are all normal, except I don't have results on

>>> C2. They are 18 months old, have normal immune globulins,

>>> lymphocyte numbers and no serious infections. The smaller twin

>>> hasn't needed hospitalization since March, even though she has had

>>> a couple URIs since then - probably because of the season, growth

>>> and better asthma control. So, they were sent to me for consult

>>> because of the low ch50. Since the testing is sensitive to sample

>>> handling, I thought to repeat it and it is still low. I cannot

>>> reconcile the history of no serious infections with low ch50 but

>>> normal complement levels. Is this just a testing aberration? Any

>>> suggestions/ideas?

>>> 

>>> Thanks!

>>> Ashish Kumar

>>> 

>>> Ashish Kumar, MD, PhD

>>> Assistant Professor

>>> Cincinnati Children's Hospital Medical Center

>>> Cincinnati, OH

>>> 

>>> 

>> 

>> 

>> <dmvascon.vcf>

> 




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