Response to M. tuberculosis selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis

A pilot study

Delia Goletti, Stefania Carrara, Harriet Mayanja-Kizza, Joy Baseke, Michael Angel Mugerwa, Enrico Girardi, Zahra Toossi

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Tuberculosis (TB) is the most frequent co-infection in HIV-infected individuals still presenting diagnostic difficulties particularly in developing countries. Recently an assay based on IFN-gamma response to M. tuberculosis RD1 peptides selected by computational analysis was developed whose presence is detected during active TB disease. Objective of this study was to investigate the response to selected RD1 peptides in HIV-1-infected subjects with or without active TB in a country endemic for TB and to evaluate the change of this response over time. Methods: 30 HIV-infected individuals were prospectively enrolled, 20 with active TB and 10 without. Among those with TB, 12 were followed over time. IFN-gamma response to selected RD1 peptides was evaluated by enzyme-linked immunospot (ELISPOT) assay. As control, response to RD1 proteins was included. Results were correlated with immune, microbiological and virological data. Results: Among patients with active TB, 2/20 were excluded from the analysis, one due to cell artifacts and the other to unresponsiveness to M. tuberculosis antigens. Among those analyzable, response to selected RD1 peptides evaluated as spot-forming cells was significantly higher in subjects with active TB compared to those without (p = 0.02). Among the 12 TB patients studied over time a significant decrease (p = <0.007) of IFN-gamma response was found at completion of therapy when all the sputum cultures for M. tuberculosis were negative. A ratio of RD1 peptides ELISPOT counts over CD4+ T-cell counts greater than 0.21 yielded 100% sensitivity and 80% specificity for active TB. Conversely, response to RD1 intact proteins was not statistically different between subjects with or without TB at the time of recruitment; however a ratio of RD1 proteins ELISPOT counts over CD4+ T-cell counts greater than 0.22 yielded 89% sensitivity and 70% specificity for active TB. Conclusion: In this pilot study the response to selected RD1 peptides is associated with TB disease in HIV-infected individuals in a high TB endemic country. This response decreases after successful therapy. The potential of the novel approach of relating ELISPOT spot-forming cell number and CD4+ T-cell count may improve the possibility of diagnosing active TB and deserves further evaluation.

Original languageEnglish
Article number11
JournalBMC Infectious Diseases
Volume8
DOIs
Publication statusPublished - Jan 28 2008

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Pulmonary Tuberculosis
Tuberculosis
HIV
Peptides
CD4 Lymphocyte Count
T-Lymphocytes
Enzymes
Enzyme-Linked Immunospot Assay
Sensitivity and Specificity
Proteins
Sputum
Coinfection
Artifacts
Developing Countries

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

Response to M. tuberculosis selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis : A pilot study. / Goletti, Delia; Carrara, Stefania; Mayanja-Kizza, Harriet; Baseke, Joy; Mugerwa, Michael Angel; Girardi, Enrico; Toossi, Zahra.

In: BMC Infectious Diseases, Vol. 8, 11, 28.01.2008.

Research output: Contribution to journalArticle

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abstract = "Background: Tuberculosis (TB) is the most frequent co-infection in HIV-infected individuals still presenting diagnostic difficulties particularly in developing countries. Recently an assay based on IFN-gamma response to M. tuberculosis RD1 peptides selected by computational analysis was developed whose presence is detected during active TB disease. Objective of this study was to investigate the response to selected RD1 peptides in HIV-1-infected subjects with or without active TB in a country endemic for TB and to evaluate the change of this response over time. Methods: 30 HIV-infected individuals were prospectively enrolled, 20 with active TB and 10 without. Among those with TB, 12 were followed over time. IFN-gamma response to selected RD1 peptides was evaluated by enzyme-linked immunospot (ELISPOT) assay. As control, response to RD1 proteins was included. Results were correlated with immune, microbiological and virological data. Results: Among patients with active TB, 2/20 were excluded from the analysis, one due to cell artifacts and the other to unresponsiveness to M. tuberculosis antigens. Among those analyzable, response to selected RD1 peptides evaluated as spot-forming cells was significantly higher in subjects with active TB compared to those without (p = 0.02). Among the 12 TB patients studied over time a significant decrease (p = <0.007) of IFN-gamma response was found at completion of therapy when all the sputum cultures for M. tuberculosis were negative. A ratio of RD1 peptides ELISPOT counts over CD4+ T-cell counts greater than 0.21 yielded 100{\%} sensitivity and 80{\%} specificity for active TB. Conversely, response to RD1 intact proteins was not statistically different between subjects with or without TB at the time of recruitment; however a ratio of RD1 proteins ELISPOT counts over CD4+ T-cell counts greater than 0.22 yielded 89{\%} sensitivity and 70{\%} specificity for active TB. Conclusion: In this pilot study the response to selected RD1 peptides is associated with TB disease in HIV-infected individuals in a high TB endemic country. This response decreases after successful therapy. The potential of the novel approach of relating ELISPOT spot-forming cell number and CD4+ T-cell count may improve the possibility of diagnosing active TB and deserves further evaluation.",
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T2 - A pilot study

AU - Goletti, Delia

AU - Carrara, Stefania

AU - Mayanja-Kizza, Harriet

AU - Baseke, Joy

AU - Mugerwa, Michael Angel

AU - Girardi, Enrico

AU - Toossi, Zahra

PY - 2008/1/28

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N2 - Background: Tuberculosis (TB) is the most frequent co-infection in HIV-infected individuals still presenting diagnostic difficulties particularly in developing countries. Recently an assay based on IFN-gamma response to M. tuberculosis RD1 peptides selected by computational analysis was developed whose presence is detected during active TB disease. Objective of this study was to investigate the response to selected RD1 peptides in HIV-1-infected subjects with or without active TB in a country endemic for TB and to evaluate the change of this response over time. Methods: 30 HIV-infected individuals were prospectively enrolled, 20 with active TB and 10 without. Among those with TB, 12 were followed over time. IFN-gamma response to selected RD1 peptides was evaluated by enzyme-linked immunospot (ELISPOT) assay. As control, response to RD1 proteins was included. Results were correlated with immune, microbiological and virological data. Results: Among patients with active TB, 2/20 were excluded from the analysis, one due to cell artifacts and the other to unresponsiveness to M. tuberculosis antigens. Among those analyzable, response to selected RD1 peptides evaluated as spot-forming cells was significantly higher in subjects with active TB compared to those without (p = 0.02). Among the 12 TB patients studied over time a significant decrease (p = <0.007) of IFN-gamma response was found at completion of therapy when all the sputum cultures for M. tuberculosis were negative. A ratio of RD1 peptides ELISPOT counts over CD4+ T-cell counts greater than 0.21 yielded 100% sensitivity and 80% specificity for active TB. Conversely, response to RD1 intact proteins was not statistically different between subjects with or without TB at the time of recruitment; however a ratio of RD1 proteins ELISPOT counts over CD4+ T-cell counts greater than 0.22 yielded 89% sensitivity and 70% specificity for active TB. Conclusion: In this pilot study the response to selected RD1 peptides is associated with TB disease in HIV-infected individuals in a high TB endemic country. This response decreases after successful therapy. The potential of the novel approach of relating ELISPOT spot-forming cell number and CD4+ T-cell count may improve the possibility of diagnosing active TB and deserves further evaluation.

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