[PAGID] Puzzling patient with high normal IgG levels but no antibody responses to vaccines

[Torgerson, Troy]

Ashish Kumar has a patient with a similarly unusual story - I don't know
if he is on the PAGID listserve but I have cc'd this to him so he can
hopefully provide more of the clinical details.  Essentially very low B
cell numbers but normal/near normal IgG levels.  We evaluated Btk and
expression was normal in platelets by flow cytometry.  When we sequenced
the gene we found a previously unreported point mutation in the kinase
domain that doesn't show up in any of the SNP databases.  Btk-base shows
several point mutations in residues 4-5 base pairs up and downstream but
only a nonsense (stop) codon mutation at the same location.  We are not
yet sure whether this mutation affects Btk function but this will be a
key question.  Since Btk is expressed, it is theoretically possible that
this could generate a hypomorphic Btk that could allow a few B cells to
slip through development and start churning out antibody in response to
activating signals but no specific Ab responses due to the limited
number of clones - or NOT??  

 

Best,

 

TT

 

Troy R. Torgerson MD PhD

Attending Physician, Pediatric Immunology/Rheumatology

Co-Director Immunodeficiency Molecular Diagnostic Lab

307 Westlake Ave. North

Suite 300

Seattle, WA  98109

 

Tel (206) 987-7450

Fax (206) 987-7310

________________________________

From: pagid-bounces at list.clinimmsoc.org
[mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of HOWARD M
LEDERMAN
Sent: Thursday, July 12, 2007 10:22 AM
To: PAGID LISTSERV
Cc: Guerrerio, Pamela A
Subject: [PAGID] Puzzling patient with high normal IgG levels but no
antibody responses to vaccines

 

I have seen pts with low normal IgG levels but poor antibody responses,
but this case seems to be way out of my experience.  Are there any
specific diagnostic tests that I should be considering?  

--------- ----------- ------------- ------------ --------------
------------ ---------- -------------

J.S. is a 10-month-old Caucasian male who had no significant infections
until 8 mos of age when he developed fever (T=104), lethargy and poor
appetite.  A full sepsis workup was conducted and his blood culture grew
Pseudomonas aeruginosa in 24 hrs.  His left tympanic membrane
spontaneously ruptured during his hospitalization and cultures also grew
pseudomonas.   A head CT was normal except for bilateral middle ear
opacification.  A chest x-ray was normal.  An abdominal ultrasound was
normal.  

 

An immunodeficiency workup showed virtually no CD19+ B-cells (0-2%;
11-169/cu mm) with normal numbers of T (90% CD3, 68% CD4 = 4467/cu mm,
21% CD8 = 1349) and NK (6% = 368/cu mm) cells. Serum immunoglobulins
were normal for age (IgG 446 mg/dL, IgA 30 mg/dL, IgM 35 mg/dL).

 

J.S. had no other history of infections other than intermittent mild
viral upper respiratory tract symptoms.  He has had no skin infections
or urinary tract infections.  His growth has been normal. He had
received all routine childhood vaccines.

 

Subsequent lab tests have shown INCREASING IgG levels (1020 mg/dL) with
low normal IgA (34 mg/dL) and IgM (31 mg/dL). Despite the elevated IgG
levels, he had NO detectable IgG antibody to previously administered
standard vaccines (<0.2 mcg/ml to 14 tested pneumococcal serotypes, <
0.11 to HIB mcg/ml and <0.10 IU/ml to tetanus).  He had NO increase in
IgG Ab after booster doses of Prevnar and Hib conjugate vaccines;
tetanus increased only marginally to 0.66 IU/ml.   Repeat T and B cell
studies by FACS were essentially the same (CD19 3%; CD20 3.3 %; abs ct
140).  Serum IFE showed no evidence of a monoclonal gammopathy. PCR
tests for EBV and CMV were negative.

 

  I am open to any and all suggestions.



Howard
Howard M. Lederman, M.D., Ph.D. 
Professor of Pediatrics and Medicine 
Division of Pediatric Allergy and Immunology 
Johns Hopkins Hospital - CMSC 1102 
600 N. Wolfe Street 
Baltimore, MD 21287-3923 
Phone:  410-955-5883 
Fax:    410-955-0229 
e-mail: Hlederm1 at jhem.jhmi.edu 




CONFIDENTIALITY NOTICE:  This e-mail message, including any attachments, is for the sole use of the intended recipient(s) and may contain confidential and privileged information protected by law.  Any unauthorized review, use, disclosure or distribution is prohibited.  If you are not the intended recipient, please contact the sender by reply e-mail and destroy all copies of the original message.
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/mailman/private/pagid/attachments/20070712/3543d667/attachment.htm>