Diagnosis of T-cell Immunodeficiency

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

T-cell Immunodeficiencies (click to enlarge the image).

Bare lymphocyte syndromes include MHC class I and MHC class II deficiencies. These are primary immune deficiency disorders (PIDD) due to a lack of expression of either MHC I or MHC II.

Screening Tests for T-cell Immunodeficiency

Absolute lymphocyte count
Chest X-ray for thymus shadow in the newborn period
Delayed skin hypersensitivity to recall antigens
Quantitation of T-cell subsets
Candida (most cost effective), MMR, Histoplasma, Diphtheria
One-test sensitivity ~ 65%
Three tests ~ 96%
In the past: dinitrochlorobenzene (DNCB) 2.5% followed in 3-4 weeks by 0.1% to see if “sensitized”

Delayed-type hypersensitivity (DTH) response

The standardized DTH test includes Candida, tetanus, mumps, and TB. Trichophyton is also commonly used. However, the only FDA-approved reagents for DTH are PPD, Candida and mumps.

Advanced T-cell testing

Lymphocyte proliferative response to mitogens, Ag, and allogenic cells
Lymphocyte mediated cytotoxicity – NK and ADCC activity
Production of cytokines, TH2/TH1 and functional response to cytokines
Signal transduction studies
Northern blot analysis for mRNA

Formation of TRECs

During their passage through the thymus, T-cell precursors rearrange their TCR genes. There are excisions of segments of DNA, the ends are ligated to form small circles called T-cell receptor excision circles (TRECs).

T-cell receptor excision circles (TRECs) can be used as a routine newborn screening protocol for SCID. DNA was extracted from DBSs NBS cards, and real-time quantitative PCR determined the number of TRECs (dried blood spots (DBSs), newborn screening (NBS) cards). No TRECs were detected in either the SCID or naive T-cell-depleted samples.

Population-based screening for SCID in neonates: The winner is T-cell receptor excision circles. JACI, 2012. See the TRECs figure here: http://goo.gl/dAXHv

Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).


In SCID, the younger the age of the patient at the time of transplantation, the better the prognosis. There is a 95% survival rate in an infant who undergoes a transplant before 3 months of age. After six months, the survival rate decreases dramatically, to 50%.


Screening for T-cell lymphopenia and SCID recommended as an addition to the newborn screening programs in all states. Expert Rev Clin Immunol. 2011 Nov;7(6):761-8.

The state of Wisconsin approach to newborn screening for SCID: 5 infants with SCID detected in 3 years. JACI, 2012.

Published: 08/29/2009
Updated: 03/09/2012

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