[CIS-PAGID] low ch50 with normal complement levels, another case.

[Abraham, Roshini S., Ph.D.]

Dr. Kingston,

 

In June of 2009 we (Mayo Clinic) discontinued the quantitative antigen
tests for C6, C7, C8 and C9 and offer only the functional assay for
these complement components.  The C9 result that you show below as being
performed at Mayo was a functional test and the reference values
provided are the reference values for our C9 functional assay.  It
appears that somehow the word "functional" may have been cut out off the
test report.

 

If you would like to cross-check the results again, please contact me
offline with patient name, date of testing and DOB and I can have the
lab retrieve the actual results and verify them with what you have.

 

Roshini

 

 

Roshini Sarah Abraham, Ph.D., D(ABMLI) 
Director, Cellular & Molecular Immunology Laboratory 
Department of Laboratory Medicine and Pathology 
Mayo Clinic 




 

 

 

 

________________________________

From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Nancy Kingston
Sent: Tuesday, November 23, 2010 12:27 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] low ch50 with normal complement levels,another
case.

 

Further test results have been released today:

AH50 65 units/ml (77-159 units/ml), low as suspected

MBL 1.65 mcg/ml (.03-4.94 mcg/ml)

Factor I   28.7mcg/ml (29.3-58.5mcg/ml)

Factor P is still pending.

 

Again, I do have the patient on antibiotic prophylaxis.  I will plan him
to have meningococcal vaccine.

I have not found any further data on the use of IV or subcutaneous IgG
replacement in these patients, and would welcome your thoughts on this.

Thank you again,

Nancy

--- On Tue, 11/23/10, dmvascon at usp.br <dmvascon at usp.br> wrote:

	
	From: dmvascon at usp.br <dmvascon at usp.br>
	Subject: Re: [CIS-PAGID] low ch50 with normal complement levels,
another case.
	To: pagid at list.clinimmsoc.org
	Date: Tuesday, November 23, 2010, 4:04 PM

	Dear Nancy
	
	Previous comments were very elucidative. With these new results
it is important to wonder that in the case of C6 deficiency, APH50 will
be probably low as CH50.
	Deficiency of Membrane attack complex components usually present
with infectious manifestations associate to encapsulated bacteria, most
commonly meningococcus.
	C9 deficient patients are usually asymptomatic, as MAC formed by
C5b through C8 is sufficient to lysis bacteria. Moreover, C9 deficiency
is very common in asians (in Japan is approximately 1:1000, if I
remember well).
	
	All the best,
	
	Dewton Vasconcelos
	
	University of Sao Paulo School of Medicine
	
	
	Citando Nancy Kingston <nwk19 at yahoo.com
<http://us.mc594.mail.yahoo.com/mc/compose?to=nwk19@yahoo.com> >:
	
	>  Thanks for your comments so far.  Regarding these, I looked
again through the patients multiple past labs and found corrected
results...C6 and C9 are low.  The labs are reported as follows:
	> C1 function 151970 units/ml (75672-190932 Units/ml) performed
by Cleveland Clinic
	> C2 1.4 mg/dL(1.0-4.0 mg/dl) performed by Cleveland Clinic
	> C3 158 mg/dl (77-143 mg/dl) (Akron Children's)
	> C4 24 mg/dl (7-40 mg/dl) (Akron Children's)
	> C5 10 mg/dl (6-20 mg/d/) performed by Quest, Cleveland Clinic.
	> C6 Functional 16 units/ml (32-57 units/ml) from Mayo
	> C7 11 mg/dL (4-11mg/dl) ARUP
	> C8 15.4 mg/dL (10.7-24.9 mg/dL) Quest/Cleveland Clinic
	> C9 26 unit/ml (37-61 unit/mL) Mayo/Cleveland Clinic
	>  
	> C6 and C9 were both performed at Mayo, but the C6 is reported
as functional and the C9 is not.  Is anyone familiar with the Mayo lab
that could answer this?  I will have my lab investigate this.  I am
anxiously awaiting the rest of the results (AH50, MBL and the Factor I
and P).
	> Thank you for your comments,
	> Nancy
	> --- On Mon, 11/22/10, Patsy Giclas <giclasp at njhealth.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=giclasp@njhealth.org> >
wrote:
	> 
	> 
	> From: Patsy Giclas <giclasp at njhealth.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=giclasp@njhealth.org> >
	> Subject: Re: [CIS-PAGID] low ch50 with normal complement
levels, another case.
	> To: "pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>
" <pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>

>

	> Date: Monday, November 22, 2010, 9:03 PM
	> 
	> 
	> Re the question on anti-complement antibodies:
	> 
	> Autoantibodies have been documented for the collagen-like
region (CLR) of
	> C1q, associated with HUVS and SLE, C1-inhibitor - various
regions,
	> associated with acquired angioedema, C3bBb (=C3NeF),
associated with MPGN2
	> and SLE, factor H, associated with aHUS, factor B (maybe a
variant of C3NeF)
	> also with aHUS, and sporadic unconfirmed antibodies against
other complement
	> proteins. Most of these antibodies are associated with
decreased function of
	> the antigen-component, but some, like C3NeF, enhance function.
Most of
	> these antibodies don't result in CH50 of 0 but it could easily
be low,
	> especially if the resulting immune complex activated
complement in addition
	> to inhibiting a component.
	> 
	> Re Dr Wasserbauer's patient:
	> 
	> There are dysfunctional forms of several of the complement
components, so I
	> support Dr Raasch's question about doing the functional assay.
I'd wait
	> until the AH50 results are in, though, rather than doing all
the components.
	> 
	> 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
<http://us.mc594.mail.yahoo.com/mc/compose?to=giclasp@njhealth.org> 
	> 
	> 
	>> From: "raas0027 at umn.edu
<http://us.mc594.mail.yahoo.com/mc/compose?to=raas0027@umn.edu> "
<raas0027 at umn.edu
<http://us.mc594.mail.yahoo.com/mc/compose?to=raas0027@umn.edu> >
	>> Reply-To: "pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>
" <pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>

>

	>> Date: Mon, 22 Nov 2010 12:51:52 -0700
	>> To: "pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>
" <pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>

>

	>> Subject: Re: [CIS-PAGID] low ch50 with normal complement
levels, another case.
	>> 
	>> Hi Nancy,
	>> 
	>> You mentioned that previous levles of C1-4, C7-9 were normal.
Were these
	>> levels from FUNCTIONAL hemolytic assays, QUANTITATION of the
individual
	>> proteins (e.g. by RID or nephelometry) or both?
	>> 
	>> TO ALL: Autoantibodies to some complement components have
been described
	>> (e.g. C1q and C3 nephritic factor). What about C1-9, for
example?
	>> 
	>> Regards,
	>> 
	>> Jason
	>> 
	>> Jason Raasch, MD
	>> 
	>> Midwest Immunology Clinic
	>> 15700 37th Ave N
	>> Suite 110
	>> Plymouth, MN 55446
	>> 
	>> (Phone) 763.577.0008
	>> (FAX)   763.5770192
	>> 
	>> 
	>> On Nov 22 2010, Nancy Kingston wrote:
	>> 
	>>> Dear Colleagues,
	>>   I, too have been referred a patient this month with a CH50
of 0.  I would
	>> like to refer you to a helpful review on the work up of
complement
	>> deficiency. (J Allergy Clin Immunol. 2004 Apr;113(4):585-93;
quiz 594.) I
	>> would like your suggestions on my patient as well.
	>>>  
	>>   The patient is a 3 yo male with history of recurrent sinus
infections
	>> requiring IV antibiotics since about 1 1/2 yrs old. There is
no family hx
	>> of immune deficiency or autoimmune disorder.   He had been
seeing an
	>>  infections disease specialist  for this and,  on one
occasion,  had
	>> gotten a dose of IVIG.  In the last six months his CH50 has
been checked 3
	>> times and has been 0.  ID has sent C1, C2, C3, C4, C7, C8, C9
on the
	>> pateint and the levels were all normal.  He had been seen my
another
	>> immunologist within the last year and had normal
immunoglobulins and
	>> several normal antibody titers (tetanus, pneumococcal, h.
influenza). 
	>> They had also checked neutrophil function, which was normal.
	>>>  
	>>   He does have subtle inflammation in the lower extremities
and knee joints
	>> comfirmed by an orthopod. 
	>>>  
	>>   He recently complained of headache, back pain and
photosensitivity, s/p
	>> one week of ceftriaxone, but on exam/ work up,  was negative
for
	>> meningitis.  He was also on prophylactic bactrim at the time.
	>>>  
	>>   He recently has sinusitis symptoms, but when I checked and
xray, it was
	>> completely normal.
	>>>  
	>>   I have gotten back a normal C5 and C 6 this week.  I am
awaiting AH50,
	>> MBL, Factor I and Factor P.
	>>> As mentioned, I do have him on antibiotic prophylaxis as
well as naproxen.
	>>   The mother is hoping for IgG replacement as she thought
that the dose he
	>> had gotten previously was helpful.  On literature review, I
have only seen
	>> prophylactic antibiotics as the therapy in general. 
	>>> What are your thoughts on IgG replacement for this patient? 
	>>> Pending the above labs, do you have any further suggestions
for lab work?
	>>> Thank you for your suggestions,
	>>>  
	>>> Nancy Wasserbauer, DO
	>>> Akron Children's Hospital
	>>> Allergy/Immunology
	>>> 
	>>> 
	>>> 
	>>> From: Anita Gewurz <agewurz at rush.edu
<http://us.mc594.mail.yahoo.com/mc/compose?to=agewurz@rush.edu> >
	>>> Subject: Re: [CIS-PAGID] low ch50 with normal complement
levels?
	>>> To: pagid at list.clinimmsoc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=pagid@list.clinimmsoc.org>

	>>> Cc: "Ashish Kumar" <Ashish.Kumar at cchmc.org
<http://us.mc594.mail.yahoo.com/mc/compose?to=Ashish.Kumar@cchmc.org> >
	>>> Date: Tuesday, November 16, 2010, 2:25 AM
	>>> 
	>>> 
	>>> 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.a
spx
	>> .
	>>> 
	>>> 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
<http://us.mc594.mail.yahoo.com/mc/compose?to=dmvascon@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
<http://us.mc594.mail.yahoo.com/mc/compose?to=Ashish.Kumar@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>
	>>> 
	>>> 
	>>> 
	>>> 
	>>>      
	>> 
	>> --
	>> Jason Raasch, MD
	>> 
	>> Midwest Immunology Clinic
	>> 15700 37th Ave N
	>> Suite 110
	>> Plymouth, MN 55446
	>> 
	>> (Phone) 763.577.0008
	>> (FAX)   763.5770192
	>> 
	> 
	> 
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