Role of dormancy survival regulator and resuscitation-promoting factors antigens in differentiating between active and latent tuberculosis: a systematic review and meta-analysis

Dormancy survival regulator (DosR) and resuscitation-promoting factor (Rpf) antigens of Mycobacterium tuberculosis are activated during dormant phase of tuberculosis (TB). This study evaluates the differential immunogenicity potentials of DosR and Rpf antigens in individuals with latent tuberculosis infection (LTBI) and active TB patients.

After a literature search in electronic databases, studies were selected by following precise eligibility criteria. Outcomes were synthesized systematically, and meta-analyses were performed to estimate standardized mean differences (SMDs) in interferon-gamma (IFNγ) levels, and IFNγ positive immune cells between individuals with LTBI and active TB patients.

Twenty-six studies (1278 individuals with LTBI and 1189 active TB patients) were included. DosR antigens Rv0569 (Standardized mean difference; SMD 2.44 [95%CI: 1.21, 3.66]; p < 0.0001), Rv1733c (SMD 0.60 [95%CI: 0.14, 1.07]; p = 0.011), Rv1735c (SMD 1.16 [95%CI: 0.44, 1.88]; p = 0.002), Rv1737c (SMD 1.26 [95%CI: 0.59, 1.92]; p < 0.0001), Rv2029c (SMD 0.89 [95%CI: 0.35, 1.42]; p = 0.002), RV2626c (SMD 1.24 [95%CI: 0.45, 2.02); p = 0.002), and Rv2628 (SMD 0.65 [95%CI: 0.38, 0.91]; p < 0.0001) and Rpf antigens Rv0867c (SMD 1.33 [95%CI: 0.48, 2.18]; p = 0.002), Rv1009 (SMD 0.65 [95%CI: 0.05, 1.25]; p = 0.034), and Rv2450c (SMD 1.54 [95%CI: 0.92, 2.16]; p < 0.0001) elicited higher IFNγ levels in individuals with LTBI in comparison with active TB patients. IFNγ-positive immunoresponsive cells were significantly higher in individuals with LTBI than in active TB patients for antigens Rv1733c (SMD 1.02 [95%CI: 0.15, 1.88]; p = 0.021), Rv2029c (SMD 0.57 [95%CI: 0.05, 1.09]; p = 0.031), and Rv2628 [SMD 0.38 [95%CI: 0.15, 0.61]; p = 0.001).

DosR antigens Rv0569, Rv1733c, Rv1735c, Rv1737c, RV2626c, Rv2628, and Rv2029c, and Rpf antigens Rv0867c, Rv1009, and Rv2450c are found to elicit immune responses differently in individuals with LTBI and active TB patients.