Soluble Programmed Death-Ligand 1 (sPD-L1) is Elevated in Aggressive Prostate Cancer Disease Among African Men.

INTRODUCTION: Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1)-targeted immunotherapies have become a new mode of treatment for several tumours; however, there is limited evidence on the expression and prognostic value of PD-1/PD-L1 in prostate cancer, especially in African men. METHODS: Plasma concentrations of PD-L1/PD-1 were assessed using enzyme-linked immunosorbent assay in patients with prostate cancer and normal healthy controls at the Uganda Cancer Institute. The associations between plasma PD-L1/PD-1 concentration levels and serum prostate-specific antigen (PSA) levels, Gleason scores, age, and body mass index (BMI) were determined. RESULTS: We found significant differences in the median plasma concentrations of PD-L1 and PD-1 immune checkpoint molecules between prostate cancer cases and normal healthy controls of 0.285 vs 0.035 (p = 0.001) and 0.596 vs 0.355 (p = 0.017), respectively. We found no significant association between age, serum PSA levels, BMI and Gleason scores, and PD-1 among patients with prostate cancer and controls. However, elevated levels of PD-L1 were significantly associated with higher Gleason scores among patients with prostate cancer (p = 0.014). CONCLUSIONS: Elevated PD-L1 levels were statistically significantly linked to high Gleason scores. These results may guide clinicians in assessing the prognosis of patients individually and selecting patients who will be suitable candidates for anti-PD-L1 immunotherapy.

Sero-diagnosis of Active Mycobacterium tuberculosis Disease among HIV Co-infected Persons using Thymidylate Kinase based Antigen and Antibody Capture Enzyme Immuno-Assays.

BACKGROUND: Clinical and laboratory diagnosis of Active Tuberculosis (ATB) and latent Mycobacterium Tuberculosis (M. tuberculosis) infections (LTBI) among people living with HIV/AIDS (PLWHA) presents formidable challenges. In the past, WHO issued an advisory against the use of existing TB sero-diagnostics. Emerging evidence, however, points to a precision of TB sero-diagnostics based on secretory rather than structural M. tuberculosis antigens. We hypothesized that secretory levels of M. tuberculosis thymidylate kinase (TMKmt) can Designate ATBI from LTBI and no TB (NTB). Here, we report in-house validation studies of levels of TMKmt antigen (Ag) and host specific TMKmt antibody (Ab) amongst HIV +ve and HIV -ve participants. METHODS AND RESULTS: Direct TMKmt Ag and host specific IgG Ab detection EIAs were conducted on broadly consented, stored serum (N=281[Ag] vs. 214 [Ab] respective) samples stratified as either HIV +ve or HIV-ve ATB relative to LTBI and No TB. On one hand, UG-peptide 1 and its PAb-based EIAs accurately diagnosed ATB relative to LTBI and NTB among HIV +ve subjects {irrespectively: (a) Ag detection ATB=OD>0.490; 95% CI: 0.7446 to 0.8715 vs. LTBI=OD<0.490; 95% CI 0.4325 to 0.4829 vs. NTB=OD<0.26; 95% CI 0.1675 to 0.2567 and (b) TMKmt specific IgG detection ATB=OD>1.00; 95% CI 1.170 to 1.528 [HIV +ve] and 2.044 to 2.978 [HIV -ve] respectively vs. LTBI=OD<1.00; 95% CI 0.2690 to 0.6396 vs. NTB=OD<; 95% CI 0.1527 to 0.8751}. HIV -ve ATB presented with Ag levels greater than NTB and less than LTBI (i.e. ATB -ve=<0.490 ODs>0.26), but displayed better ant-TMKmt IgG responses (OD>2.00; 95% CI 2.044 to 2.978) relative to HIV +ve ATB (OD<1.600; 95% CI 1.170 to 1.528); suggesting a better control of M. tuberculosis-septicemia. On the other hand, UG-peptide 2 and its PAb-based EIAs did not demonstrate ATB diagnostic potential regardless of HIV sero-status, except towards designating NTB. CONCLUSIONS: TMKmt Ab and Ag detecting EIAs based on UG-peptide 1 and its derivative PAb can accurately demarcate ATB from LTBI and NTB among HIV +ve subjects.