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

[Anete S Grumach]

Dear Nancy,

There is some reports of IgG subclass deficiency or reduced polyssacharide
Ab response associated with complement deficiency.
Usually the patients  respond well after vaccination to all encapsulated
bacteria and/or antibiotic prophylaxis.
You referred that your patient presented a good response to pneumococcus.
It is also established to immunize the family members against those bacteria
as contactants of the patient.
Usually, complete deficiency of complement proteins of terminal pathway
present with undetectable CH50 and AH50.
It is possible to have partial C6 deficiency and it could be worsen by the
immunologic immaturity of the child.
Properdin deficiency is X linked and it is not associated with undetectable
hemolytic assays for complement evaluation.

best regards

Anete
Faculty of Medicine ABC,
São Paulo State, Brazil



2010/11/23 Nancy Kingston <nwk19 at yahoo.com>


> 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.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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