Q:

12/17/2012
66 yo female with Hx severe recurrent pseudomona and E. Coli sinusitis. Non-diabetic and CF has been r/o. Immune w/u: normal Igs, nl titers to protein and polysaccharide antigens, nl lymphocyte subsets but a very significantly reduced lymphocyte proliferation response to Tetanus and candida, with normal response to mitogens. No use of steroids or other immunosuppresants.

Question: could there be an abnormality in the TCR signaling pathway that accounts for the low T cell response to antigens but normal to mitogens in the presence of normal humoral response to T cell-dependent antigens? If so, who could help me to do the right testing to figure it out? Thanks.

A:

Thank you for your inquiry.

I am not aware of any specific T cell abnormality that would account for the problem in the patient you described. However, it is not unusual to have patients with chronic sinusitis colonized by both E. coli and pseudomonas after surgeries and multiple antibiotic administrations .I have always assumed that this colonization resulted from the use of antibiotics and local diminished immune responses related to sinus surgery.

However, I am going to ask Dr. Francisco Bonilla an internationally recognized authority in immunodeficiency disorders for his help in this regard. As soon as I receive a response, I will forward it to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We received a response from Dr. Francisco Bonilla. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Francisco Bonilla:
There are not enough details to make a good answer yet. Speaking generally, I think it is possible that there could be a T cell signaling defect that could cause antigen response to be abnormal with a normal mitogen response and apparent normal antibody response. There are some missing details: a) antibody titers may be normal, but antibody "quality" may be poor, this is a theoretical observation, mainly. You could consider looking at pneumococcal antibody avidity, the test is available from IBT lab, this is potentially useful if the avidity of antibodies for conjugate vaccine types are low, but interpretation is still being worked out; b) lymphocyte subsets are "normal", but if you are speaking of only the major subsets (CD3/4/8, B, NK) then there could still be significant abnormalities in the makeup of smaller T cell and B cell populations that could be clinically significant, there are many labs including our lab (Boston Children's) or the NIH and others that can do more detailed lymphocyte phenotype analysis; c) how low is the "reduced" proliferation to tetanus and candida? These experiments are very variable and interpretation is sometimes not straightforward, I would want to see it replicated at least once, and look carefully at the lab's normal reference ranges. If you like, we can perform some additional analyses for you.

Tony Bonilla

AAAAI - American Academy of Allergy Asthma & Immunology