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

[Patsy Giclas]

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




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