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Tuberculosis, more commonly referred to as TB, is an infectious disease stemming from Mycobacterium tuberculosis. While it primarily impacts the lungs, TB can also affect other body areas. Given its severity and global impact, timely and accurate diagnosis is crucial for controlling its spread and improving patient outcomes.
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Immune activation from M. tuberculosis screening tests predicts mortality.

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A lower T-cell response measured by interferon-gamma release assays (IGRAs) is linked to increased mortality risk in older adults. This common test can help identify individuals with impaired immune function and higher mortality risk.

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Area of Science:

  • Immunology
  • Gerontology
  • Public Health

Background:

  • Aging is associated with impaired immune responses, but linking these to clinical outcomes is challenging.
  • Interferon-gamma release assays (IGRAs) measure T-cell responses to tuberculosis antigens and include a mitogen stimulation control.
  • The difference between mitogen-stimulated and unstimulated T-cell responses (mitogen-nil) is used for IGRA validity but may also reflect immune function.

Purpose of the Study:

  • To investigate the association between the mitogen-nil measure from IGRAs and all-cause mortality.
  • To determine if IGRA mitogen-nil can serve as a biomarker for impaired immune response and mortality risk in an aging population.

Main Methods:

  • Retrospective analysis of outpatient IGRA data from a large health system.
  • Included 16,104 individuals with negative or indeterminate IGRAs, excluding those on dialysis or immunosuppressants.
  • Kaplan-Meier analysis and Cox regression assessed the association of mitogen-nil values with mortality at 6 months, 1 year, and 5 years.

Main Results:

  • Lower mitogen-nil values (indicating weaker T-cell response to mitogen) were associated with significantly higher all-cause mortality.
  • For mitogen-nil values of 0-1 IU/mL compared to ≥10 IU/mL, 5-year mortality was 28% vs. 19%.
  • Cox regression showed increased hazard ratios for mortality across all time points for lower mitogen-nil values, with adjustments for lymphocyte count not altering associations.

Conclusions:

  • A diminished T-cell response to mitogen stimulation, as measured by IGRA mitogen-nil, is a significant predictor of increased mortality.
  • IGRAs, commonly used for tuberculosis screening, can potentially be utilized to risk-stratify patients based on immune function.
  • The mitogen-nil measure offers a practical laboratory phenotype for assessing immune impairment in aging individuals.