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

[Patsy Giclas]

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



> From: "raas0027 at umn.edu" <raas0027 at umn.edu>

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

> Date: Mon, 22 Nov 2010 12:51:52 -0700

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

>> 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

> 




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