Beryllium-specific CD4+ T cells in blood as a biomarker of disease progression.

Abstract

BACKGROUND:

CD4(+) T cells are responsible for the progressive lung damage seen in patients with chronic beryllium disease (CBD), a granulomatous lung disorder in which antigen-specific, T(H)1-type, cytokine-secreting T cells have been characterized. Compared with those seen in beryllium (Be)-sensitized subjects, increased numbers of Be-responsive T cells are present in the blood of patients with CBD.

OBJECTIVE:

The aim of this study was to determine whether the number of Be-specific T cells in blood predicted the development of CBD in a cohort of Be-exposed subjects.

METHODS:

Using IFN-γ ELISpot and proliferation-based assays, we determined the frequency and proliferative capacity of Be-responsive T cells in blood.

RESULTS:

Compared with the Be lymphocyte proliferation test, which detected an abnormal Be-induced proliferative response in 11 (4.2%) of 260 workers from a Be-machining facility, the IFN-γ ELISpot detected a sensitization rate of 10% (χ(2) = 55.7, P < .0001). A significant positive correlation was also noted between the number of Be-responsive CD4(+) T cells in the blood and lung tissue of patients with CBD. Importantly, the transition from Be sensitization to CBD was associated with an increased number of antigen-specific T cells in blood.

CONCLUSION:

These findings have important implications for Be-induced disease and potentially other immune-mediated disorders, suggesting that the frequency of antigen-specific T cells in blood can serve as a noninvasive biomarker to predict disease development and severity of the Be-specific CD4(+) T-cell alveolitis.

• Authors: Allison K Martin, Douglas G Mack, Michael T Falta, Margaret M Mroz, Lee S Newman, Lisa A Maier, Andrew P Fontenot
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 128 Issue 5 Pg. 1100-6.e1-5 (Nov 2011) ISSN: 1097-6825 [Electronic] United States
• PMID: 21943943 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Biomarkers

Topics

• Adult
• Aged
• Berylliosis (blood, immunology)
• Biomarkers (blood)
• CD4-Positive T-Lymphocytes (immunology)
• Disease Progression
• Enzyme-Linked Immunospot Assay
• Female
• Fluorescent Antibody Technique
• Humans
• Lymphocyte Activation (immunology)
• Male
• Middle Aged