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

[raas0027 at umn.edu]

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>

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

>To: pagid at list.clinimmsoc.org

>Cc: "Ashish Kumar" <Ashish.Kumar at 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.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>

>

>

>

>

>      


-- 
Jason Raasch, MD

Midwest Immunology Clinic
15700 37th Ave N
Suite 110
Plymouth, MN 55446

(Phone) 763.577.0008
(FAX)   763.5770192