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Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study.

Kim SH, Lee HJ, Kim SM, Jung JH, Shin S, Kim YH, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Han DJ - Infect Chemother (2015)

Bottom Line: We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Background: Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation.

Materials and methods: All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.

Results: A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).

Conclusion: Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

No MeSH data available.


Related in: MedlinePlus

Response to IE1 and pp65 according to the presence of CMV infection after kidney transplantation. Bars indicate medians. The Mann-Whitney U test was used to compare the differences between groups.IFN, interferon; PBMC, peripheral blood mononuclear cells; CMV, cytomegalovirus.
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Figure 2: Response to IE1 and pp65 according to the presence of CMV infection after kidney transplantation. Bars indicate medians. The Mann-Whitney U test was used to compare the differences between groups.IFN, interferon; PBMC, peripheral blood mononuclear cells; CMV, cytomegalovirus.

Mentions: On the basis of the ROC curves (Supplemental Fig. 1), we determined that the optimal cut-off values were >10 spots and > 0 spots, for the pp65 and IE1 ELISPOT assays, respectively. When we used these cut-offs, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infection, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the pp65 ELISPOT for predicting CMV infection were 44% (95% CI, 25-65), 79% (95% CI, 63-89), 57% (95% CI, 34-78), and 69% (95% CI, 54-81), respectively. However, there was not any statistical significant association between the IE1-specific ELISPOT assay and CMV infection; 14 (33%) of the 42 patients with positive IE1-specific ELISPOT results (>0 spots/2.0 × 105 cells) developed CMV infection, and 13 (48%) of the 27 patients with negative IE1-specific ELISPOT results developed CMV infection (P = 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of the IE1 ELISPOT for predicting CMV infection were 48% (95% CI, 29-68), 67% (95% CI, 50-80), 48% (95% CI, 29-68), and 67% (95% CI, 50-80), respectively. Responses to IE1 and pp65 according to the presence of CMV infection after kidney transplantation are shown in Figure 2.


Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study.

Kim SH, Lee HJ, Kim SM, Jung JH, Shin S, Kim YH, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Han DJ - Infect Chemother (2015)

Response to IE1 and pp65 according to the presence of CMV infection after kidney transplantation. Bars indicate medians. The Mann-Whitney U test was used to compare the differences between groups.IFN, interferon; PBMC, peripheral blood mononuclear cells; CMV, cytomegalovirus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4495268&req=5

Figure 2: Response to IE1 and pp65 according to the presence of CMV infection after kidney transplantation. Bars indicate medians. The Mann-Whitney U test was used to compare the differences between groups.IFN, interferon; PBMC, peripheral blood mononuclear cells; CMV, cytomegalovirus.
Mentions: On the basis of the ROC curves (Supplemental Fig. 1), we determined that the optimal cut-off values were >10 spots and > 0 spots, for the pp65 and IE1 ELISPOT assays, respectively. When we used these cut-offs, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infection, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the pp65 ELISPOT for predicting CMV infection were 44% (95% CI, 25-65), 79% (95% CI, 63-89), 57% (95% CI, 34-78), and 69% (95% CI, 54-81), respectively. However, there was not any statistical significant association between the IE1-specific ELISPOT assay and CMV infection; 14 (33%) of the 42 patients with positive IE1-specific ELISPOT results (>0 spots/2.0 × 105 cells) developed CMV infection, and 13 (48%) of the 27 patients with negative IE1-specific ELISPOT results developed CMV infection (P = 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of the IE1 ELISPOT for predicting CMV infection were 48% (95% CI, 29-68), 67% (95% CI, 50-80), 48% (95% CI, 29-68), and 67% (95% CI, 50-80), respectively. Responses to IE1 and pp65 according to the presence of CMV infection after kidney transplantation are shown in Figure 2.

Bottom Line: We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

ABSTRACT

Background: Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation.

Materials and methods: All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves.

Results: A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04).

Conclusion: Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.

No MeSH data available.


Related in: MedlinePlus