[CIS-PAGID] 16 year old with recurrent pneumonias and low CH50

[Giclas, Patsy]

Hi Mike,

We are still in the development phase for the C4 gene-copy number assay but getting closer!  I'd be happy to put a tube of his whole blood (EDTA) into the queue for the next go, but it would be strictly RUO.  As you know we have had problems with the assay for a while.  Meantime, I'd look at the C4 functionally again since that's more sensitive.  Remember that C4 has two forms: C4A and C4B.  The former binds to amino groups on proteins and is associated more with RA through decreased immune complex clearance.  The latter binds preferentially to -CHO residues and its deficiency is more likely to be found in patients with infections.  There are usually 2 genes for each form, making 4 the "normal" gene copy number, but there is wide variability in the population, ranging from no C4 genes to more than 7.  C Yung Yu in Columbus Ohio has published widely on this topic, and he may still be willing to do the test (also RUO).

Best regards,

Patsy

Patricia C. Giclas, PhD
Director, Diagnostic Complement Laboratory
Professor, Pediatric Allergy and Immunology
National Jewish Health
1400 Jackson
Denver Colorado, 80206 USA
office 303-398-1217
Fax 303-270-2128
email giclasp at njhealth.org
________________________________________
From: pagid-bounces at list.clinimmsoc.org [pagid-bounces at list.clinimmsoc.org] On Behalf Of M CLAYTON [mhclayton at msn.com]
Sent: Thursday, December 30, 2010 9:27 AM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS-PAGID] 16 year old with recurrent pneumonias and low CH50

Hi Patsy:

Thanks for your comments.  This has been a frustrating case- apart from the mixed lab results, he has been exceptionally difficult to get in for followup, and his workup has been done piecemeal in two different hospitals, orchestrated through different providers and labs.  The normal AH50 was run through the Mayo lab while he was acutely ill with the most recent pneumonia.  The recent C4 was a quantitative analysis rather than the functional assay.  The MBL assay was WNL=44.3 (>5.0 ng/ml).  Can you do the genetic analysis for C4 genes?  As for the RA, I am trying to get him in to see the rheumatologist.  Happily, he has had a good winter, so far.

Michael H. Clayton, MD, MPH
Assistant Clinical Professor
UNM Dept. of Pediatrics




> Date: Wed, 29 Dec 2010 16:04:09 -0700

> From: giclasp at njhealth.org

> To: pagid at list.clinimmsoc.org

> Subject: Re: [CIS-PAGID] 16 year old with recurrent pneumonias and low CH50

>

> Hello Mike,

>

> This is an interesting case, and it's changed in character a bit since the

> first presentation. I'm curious to know what you make of normal AH50 now

> versus the lack of alternative pathway (AP) activity on the first visit?

> How soon after the hospitalization was that specimen obtained? There were

> no AP protein deficiencies at that time, so the combination of 0 CH50 with 0

> AH50 pointed to a terminal or control protein defect. With the current

> presentation, his AH50 is normal, C1 function is low, C2 was low but then

> recovered (RF, immune complexes?), his C4 is low again (not the functional

> assay this time?), C3 and the two late components measured (C6 and C7) were

> low (again looks like activation).

>

> My guess is that there may be an underlying C4 deficiency and that the other

> complement abnormalities are related to activation, probably through the

> classical pathway but it could be the lectin pathway. Have you checked MBL?

> The lectin pathway goes through C2 and C4 also but spares C1. Without C4,

> activation by either of these pathways would be inefficient and wouldn't

> involve C3 or the terminal proteins unless the alternative pathway was

> involved like it might be with a bacterial trigger.

>

> I think your "mixed process" could explain much of what's happening. The C4

> function is a more sensitive assay than the protein quantitation, and a look

> at the number of C4 genes present would also clarify what is going on. Low

> C4 also fits with the presentation and the development of RA, if that's now

> confirmed.

>

> Happy New Year!

>

> Patsy

>

> 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: M CLAYTON <mhclayton at msn.com>

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

> > Date: Wed, 29 Dec 2010 14:46:59 -0700

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

> > Subject: [CIS-PAGID] 16 year old with recurrent pneumonias and low CH50

> >

> > I would like to present a young man to the group for advice. He is a 16 year

> > old Native American boy who lives at Santo Domingo Pueblo near Santa Fe here

> > in New Mexico. He was reportedly in good health (except for recurrent otitis

> > media as a toddler) until 18 months ago when he presented with pneumonia and

> > empyema. He was hospitalized at a private hospital, and labs at that time

> > showed a CH50 of "0", and quantitative immunoglobulins were reportedly normal.

> > Other labs included:

> >

> > AH50=0

> > Factor D=71 (127-306)

> > Factor B=92 (123-426)

> > Properidin=29.4 (22.3-67.6)

> > C3 fuction WNL (18,317 U/ml)

> > C4 function decreased =2 (nl range 40000-4300000 U/ml)

> >

> > I was not involved in his care at that point, but he was referred and lost to

> > followup for nearly 12 months. He reappeared and was again hospitalized with

> > pneumonia.

> > A blood culture on admission grew a Beta hemolytic Group B Strep. The

> > following labs were obtained:

> >

> > CH50=4

> > AH50=130

> > C1 function= 50715 (75672-190932)

> > C2=0.4 (1.0-4.0), repeated 10 days later= WNL (2.8)

> > C3=51 (62-125)

> > C4=2.5 (15-39)

> > C6 function=12.0 (32-57)

> > C7 function=35 (36-60)

> > ANA screen Negative

> > Rheumatoid Factor=45 (<15 IU/ml)

> > Diptheria IgG=.74

> > Tetanus IgG=.42

> > 8/12 pneumococcal IgG titers > 1.0 ug/ml

> >

> > Approximately 10 days after above labs:

> > C3A, C4A, C5A all WNL

> >

> > IgG, A, M, E all WNL. Immune Deficiency panel WNL.

> >

> > What conclusions can I draw from these labs? Several components were low

> > during the most recent hospitalization suggesting consumption, but the very

> > low C4 function during his initial illness and the persisting low C4 level

> > made me wonder about a C4 deficiency. Could it be a mixed process? Any

> > comments or suggestions would be welcome.

> > Thanks in advance, and Happy Holidays to all-

> >

> >

> > Michael H. Clayton, MD, MPH

> > Assistant Clinical Professor

> > UNM Dept. of Pediatrics

>

>

>

> NOTICE: This email message is for the sole use of the intended recipient(s) and may contain confidential and privileged information. Any unauthorized review, use, disclosure or distribution is prohibited. If you are not the intended recipient, please contact the sender by reply email and destroy all copies of the original message.


NOTICE: This email message is for the sole use of the intended recipient(s) and may contain confidential and privileged information. Any unauthorized review, use, disclosure or distribution is prohibited. If you are not the intended recipient, please contact the sender by reply email and destroy all copies of the original message.