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

[HOWARD M LEDERMAN]

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 
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