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

[Nacho Gonzalez]

Dear Nancy,

be careful when considering a patient as C9 deficient. In japanese people is
a common finding within normal population (I think 1 out of 5000).
Furthermore, in C9 def usually is not seen absent classical complement
activity.

Regards,

Luis Ignacio Gonzalez-Granado
Immunodeficiencies Unit.
Hospital 12 octubre. Madrid. Spain.

2010/11/23 Nancy Kingston <nwk19 at 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>* wrote:

>

>

> From: Patsy Giclas <giclasp at njhealth.org>

>

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

> case.

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