Infectious Diseases
ISSN: 2374-4235 (Print) 2374-4243 (Online) Journal homepage: http://www.tandfonline.com/loi/infd20
Potential role of serum BAFF as a biomarker in HIV infection Javier Carbone, Leticia Calahorra, Joaquin Navarro & Elizabeth Sarmiento To cite this article: Javier Carbone, Leticia Calahorra, Joaquin Navarro & Elizabeth Sarmiento (2015) Potential role of serum BAFF as a biomarker in HIV infection, Infectious Diseases, 47:4, 260-262 To link to this article: http://dx.doi.org/10.3109/00365548.2014.1001998
Published online: 17 Feb 2015.
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Date: 14 September 2015, At: 00:54
Infectious Diseases, 2015; 47: 260–262
SHORT COMMUNICATION
Potential role of serum BAFF as a biomarker in HIV infection
Downloaded by [University of California, San Diego] at 00:54 14 September 2015
JAVIER CARBONE, LETICIA CALAHORRA, JOAQUIN NAVARRO & ELIZABETH SARMIENTO From the Clinical Immunology Department, Hospital General Universitario Gregorio Maranon. Madrid, Spain
Abstract We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations ( 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.
Keywords: HIV, lymphocyte activation, BAFF, biomarker, risk factors
Introduction Chronic B-cell activation is a relevant component of HIV infection, and serum B-cell activation markers have been evaluated in this context [1]. One such marker is higher serum values of B-cell activating factor (BAFF), a cytokine that regulates the survival and selection of peripheral B cells. Biomarker use to identify the risk for development of AIDS and personalization of therapy could improve patient care. In the present study, we tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV-positive patients.
Methods We studied stored frozen serum samples obtained from 41 HIV-infected intravenous drug users recruited from 1997 to 1998 (mean age, 34 [26–49] years; 33 male, eight female). The patients were included in a prospective study to evaluate T-cell subsets as surrogate markers for development of AIDS. There was no loss of follow-up. Seventeen patients were asymptomatic (CDC category A) and 24 were symptomatic
(CDC category B) with no AIDS-defining diseases at the time of the study. The serum samples were kept frozen at –80°C in polypropylene tubes until used. Retesting of IgA levels was performed in 10 samples to assess stability. IgA concentration correlated well between frozen and fresh serum samples (R 0.99, p 0.001). Mean time from diagnosis of HIV infection was 7.3 (3–12 years). Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay (Human BAFF/BLyS/ TNFSF13B Quantikine ELISA Kit, R&D Systems Inc., Minneapolis, MN, USA). Activated CD4 and CD8 T-cell subsets were measured in fresh total blood samples using three-color flow cytometry at baseline (FACScan, Becton & Dickinson, San José, CA, USA). T-cell subsets were enumerated using FITC/PE/PerCP combined, respectively, with CD38/ HLA-DR/CD4, CD38/CD45RO/CD4, HLA-DR/ CD45RO/CD4, CD38/CD45RO/CD8 monoclonal antibodies, and isotype controls. Lymphocyte subset values are expressed as percentages of total CD4 or CD8 lymphocyte subsets. Serum BAFF concentration was also correlated with soluble immune activation factors. IgA was measured by nephelometry
Correspondence: Javier Carbone, Clinical Immunology Department, Hospital General Universitario Gregorio Maranon, Dr Esquerdo 46, 28007, Madrid, Spain. Tel: 34 91 4265180. Fax: 34 91 5866698. E-mail: [email protected] (Received 21 September 2014 ; accepted 10 December 2014 ) ISSN 2374-4235 print/ISSN 2374-4243 online © 2015 Informa Healthcare DOI: 10.3109/00365548.2014.1001998
Downloaded by [University of California, San Diego] at 00:54 14 September 2015
BAFF as a biomarker in HIV infection
Results Mean time of follow-up to the last registered visit was 109 months. Twelve of the 41 patients (29%) progressed to clinical AIDS. Mean time to development of AIDS was 32 months (interval, 1–82 months). Mean serum concentrations of BAFF were significantly higher in patients who later developed AIDS (2722 2197 vs 1905 1542 pg/mL, p 0.021). When we used the 75th percentile value of BAFF as a cut-off (2100 pg/mL), patients with higher concentrations (n 10) were at greater risk of developing AIDS (Cox regression: relative hazard [RH], 5.69; 95% confidence interval [CI], 1.79–18.15; p 0.0033). AIDS developed within the first 24 months of follow-up among HIV individuals with baseline BAFF 2100 pg/mL, while the first clinical AIDS occurred after the first 24 months in patients with lower BAFF levels (Figure 1). The lowest serum BAFF concentration (646 pg/mL) was observed in a patient who fulfilled criteria as HIV elite controller. Clinical variables that were associated with the risk for development of AIDS are presented in Table I. Regarding antiretroviral therapy, at the time of inclusion 26 patients were taking ART (n 19) or HAART (n 7). Eleven of these patients developed AIDS, seven on failing therapy. Five patients developed clinical AIDS before the introduction of HAART and two patients after HAART therapy was started. These two patients were found to have low CD4 counts (243 and 256 cells/uL), high CD8 CD38 ( 70%) and CD4 CD38 DR ( 14%) percentages and were not able to suppress viral replication. Five patients developed AIDS while on ART (four of these patients failed to control HIV viremia). Eleven patients had
Development of AIDS 1.0
.8 Cumulated Hazard
(Beckman, CA, USA); beta-2-microglobulin and neopterin were measured by radioimmunoassay (Pharmacia Diagnostics, Uppsala, Sweden and Immuno Biological, Hamburg, Germany, respectively). We selected the 75th percentile value as the cutoff point of biomarkers. Commonly used cut-off points were selected for CD4 and HIV viral load. Treatment failure was defined as a HIV viral load greater than 5000 copies/mL. Measurement of the degree of linear dependence between two variables was evaluated by Pearson correlation test. Proportional hazards models (Cox regression analysis) were performed to assess the relationship between BAFF levels and clinical outcome. Time to the onset of first clinical AIDS or latest available follow-up date were registered. The study was approved by the local ethical committee. A patient’s informed consent was obtained before examination and to perform further analysis of stored serum samples.
261
Log Rank 10.80 p= 0.001
.6 BAFF .4
> 2100 pg/mL
.2 < 2100 pg/mL 0.0 0
12 24 36 48 60 72 84 96 Time after study (months)
Figure 1. Kaplan-Meier curves shows that HIV patients with higher serum BAFF concentrations ( 2100 pg/mL) are correlated with more rapid progression into AIDS.
suppressed virus after HAART introduction. None of these patients developed AIDS. BAFF concentration and failing antiretroviral therapy at the time of inclusion remained significant risk factors for AIDS (RH, 5.02; 95% CI, 1.21–20.85; p 0.026 and RH, 5.77; 95% CI 1.51–21.90, p 0.01, respectively) in multivariate Cox regression analysis including serum BAFF, failing therapy at the time of inclusion, candidiasis, HIV status and time of HIV infection in the regression model. The risk for development of AIDS associated with BAFF concentration decreased after adjustment for absolute CD4 counts ( 350 cells/uL [RH, 3.36; 95% CI, 0.96–11.81; p 0.058]). BAFF levels remained a significant risk factor for development of AIDS after adjustment for viral load ( 400 copies/mL [RH, 4.20; 95% CI, 1.23–14.33; p 0.0219]). Moderately significant positive correlations were observed between BAFF levels and percentages of the following subsets: activated CD8 CD38 cells (Spearman coefficient, R 0.58; p 0.001); memoryactivated CD8 CD45RO CD38 (R 0.53, p 0.005); and activated CD4 CD38 DR (R 0.41, p 0.016). Interestingly, serum BAFF concentrations were not correlated with IgA serum levels (R –0.13, p 0.43), but were significantly associated with serum beta-2-microglobulin levels (R 0.52, p 0.002) and with neopterin concentrations (R 0.447, p 0.008). Discussion As we previously demonstrated for serum immunoglobulin levels [1] and CD4 and CD8 activated subsets [2], higher serum BAFF levels were an independent risk factor for development of AIDS.
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Downloaded by [University of California, San Diego] at 00:54 14 September 2015
Table I. Univariate Cox regression analysis for factors associated with risk of first clinical AIDS. Characteristics*
N
Age 34 years (mean value) Time after HIV infection 7 years (mean value) Gender (male vs female) Anti-HCV positive Anti-HBV positive HIV CDC category B vs A Candidiasis (oral or vaginal)† Bacterial pneumonia (single episode)† Herpes zoster† Taking ART Taking HAART† ART/HAART failing patients‡ Serum BAFF 2100 pg/mL (75th p) CD4 350 cells/uL Viral load 400 copies/mL CD4 CD38 DR 17% (75th p) CD8 CD38 83% (75th p) Serum IgA 292 mg/dL (75th p) Neopterin 3.42 mg/L (75th p) Beta-2-microglobulin 3.95 mg/L (75th p)
21 22 33 34 23 24 11 13 9 19 18 7 10 18 17 10 10 10 10 10
Univariate HR (95% CI) 1.36 3.23 1.16 2.42 1.76 4.11 6.47 1.84 2.32 3.17 1.92 6.55 5.69 5.41 4.19 24.96 10.04 2.79 5.54 3.34
(0.43–4.30) (0.87–11.97) (0.31–4.30) (0.31–18.75) (0.53–5.84) (0.89–18.79) (2.02–20.76) (0.58–5.82) (0.69–7.83) (0.41–24.55) (0.61–6.07) (1.89–22.71) (1.79–18.15) (1.46–20.12) (1.25–14.01) (4.7–132.4) (2.36–48.81) (0.88–8.81) (1.73–17.55) (0.98–11.30)
p 0.59 0.079 0.82 0.398 0.359 0.068 0.0017 0.29 0.17 0.27 0.27 0.0030 0.0033 0.012 0.02 0.0002 0.0018 0.07 0.0039 0.052
ART, antiretroviral therapy; HAART, highly active antiretroviral therapy; HR, hazard ratio; N, number of events; 75th p, 75th percentile. *Clinical characteristics at the time or before the sample collection. †Clinical characteristics during follow-up. ‡Patients on failing therapy at the time of inclusion.
Previous studies have shown that serum BAFF levels were significantly higher among HIV-infected patients than among controls [3,4]. Rodriguez et al. [3] described higher BAFF concentrations among HIV-positive patients with lower CD4 cell counts. We are not aware of previous reports demonstrating that higher BAFF concentrations were associated with higher activated CD8 and CD4 T-cell percentages in HIV-infected individuals. BAFF activity has been observed in effector/memory T-cells (both CD8 and CD4 subsets), indicating that BAFF has a role in T-cell activation [5]. Previous studies have also evaluated the relationship between BAFF levels and other immune cell subtypes in HIV infection. In our study we found a significant correlation between serum BAFF and neopterin levels which is a monocyte activation factor. Our data suggest that a higher BAFF serum concentration might reflect better the increased immune activation status in HIV patients as this factor acts on distinct immune cells including T-cells, B-cells, and dendritic cells. Our new data are limited in their precision due to the small sample size but support the hypothesis that higher BAFF concentrations are associated with risk for development of AIDS. The retrospective analysis of the relationship between BAFF levels and clinical outcome was another limitation of our study. However, our observations and those obtained in previous studies suggest that serum BAFF is a good
candidate for further evaluation as a nonspecific surrogate marker in HIV infection in a replicating study performed in patients using current antiretroviral regimens. Declaration of interest: The authors report no conflicts of interest. The authors have no funding to report. The authors alone are responsible for the content and writing of the paper.
References [1] Carbone J, Sarmiento E, Rodriguez-Molina JJ, Gil J, Fernandez-Cruz E. Immunoglobulin levels and prediction of progression to AIDS in HIV-infected injection drug users. AIDS Patient Care STDS. 2004;18:685–6. [2] Carbone J, Gil J, Benito JM, Navarro J, Muñóz-Fernández A, Bartolomé J, et al. Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users. AIDS 2000;14:2823–9. [3] Rodriguez B, Valdez H, Freimuth W, Butler T, Asaad R, Lederman M. Plasma levels of B- lymphocyte stimulator increase with HIV disease progression. AIDS 2003;17: 1983–2000. [4] Fontaine J, Chagnon-Choquet J, Valcke HS, Poudrier J, Roger M. High expression levels of B lymphocyte stimulator (BLyS) by dendritic cells correlate with HIV-related B-cell disease progression in humans. Blood 2011;117:145–55. [5] Huard B, Schneider P, Mauri D, Tschopp J, French LE. T cell costimulation by the TNF ligand BAFF. J Immunol 2001; 167:6225–31.
ISSN: 2374-4235 (Print) 2374-4243 (Online) Journal homepage: http://www.tandfonline.com/loi/infd20
Potential role of serum BAFF as a biomarker in HIV infection Javier Carbone, Leticia Calahorra, Joaquin Navarro & Elizabeth Sarmiento To cite this article: Javier Carbone, Leticia Calahorra, Joaquin Navarro & Elizabeth Sarmiento (2015) Potential role of serum BAFF as a biomarker in HIV infection, Infectious Diseases, 47:4, 260-262 To link to this article: http://dx.doi.org/10.3109/00365548.2014.1001998
Published online: 17 Feb 2015.
Submit your article to this journal
Article views: 30
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=infd20 Download by: [University of California, San Diego]
Date: 14 September 2015, At: 00:54
Infectious Diseases, 2015; 47: 260–262
SHORT COMMUNICATION
Potential role of serum BAFF as a biomarker in HIV infection
Downloaded by [University of California, San Diego] at 00:54 14 September 2015
JAVIER CARBONE, LETICIA CALAHORRA, JOAQUIN NAVARRO & ELIZABETH SARMIENTO From the Clinical Immunology Department, Hospital General Universitario Gregorio Maranon. Madrid, Spain
Abstract We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations ( 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.
Keywords: HIV, lymphocyte activation, BAFF, biomarker, risk factors
Introduction Chronic B-cell activation is a relevant component of HIV infection, and serum B-cell activation markers have been evaluated in this context [1]. One such marker is higher serum values of B-cell activating factor (BAFF), a cytokine that regulates the survival and selection of peripheral B cells. Biomarker use to identify the risk for development of AIDS and personalization of therapy could improve patient care. In the present study, we tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV-positive patients.
Methods We studied stored frozen serum samples obtained from 41 HIV-infected intravenous drug users recruited from 1997 to 1998 (mean age, 34 [26–49] years; 33 male, eight female). The patients were included in a prospective study to evaluate T-cell subsets as surrogate markers for development of AIDS. There was no loss of follow-up. Seventeen patients were asymptomatic (CDC category A) and 24 were symptomatic
(CDC category B) with no AIDS-defining diseases at the time of the study. The serum samples were kept frozen at –80°C in polypropylene tubes until used. Retesting of IgA levels was performed in 10 samples to assess stability. IgA concentration correlated well between frozen and fresh serum samples (R 0.99, p 0.001). Mean time from diagnosis of HIV infection was 7.3 (3–12 years). Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay (Human BAFF/BLyS/ TNFSF13B Quantikine ELISA Kit, R&D Systems Inc., Minneapolis, MN, USA). Activated CD4 and CD8 T-cell subsets were measured in fresh total blood samples using three-color flow cytometry at baseline (FACScan, Becton & Dickinson, San José, CA, USA). T-cell subsets were enumerated using FITC/PE/PerCP combined, respectively, with CD38/ HLA-DR/CD4, CD38/CD45RO/CD4, HLA-DR/ CD45RO/CD4, CD38/CD45RO/CD8 monoclonal antibodies, and isotype controls. Lymphocyte subset values are expressed as percentages of total CD4 or CD8 lymphocyte subsets. Serum BAFF concentration was also correlated with soluble immune activation factors. IgA was measured by nephelometry
Correspondence: Javier Carbone, Clinical Immunology Department, Hospital General Universitario Gregorio Maranon, Dr Esquerdo 46, 28007, Madrid, Spain. Tel: 34 91 4265180. Fax: 34 91 5866698. E-mail: [email protected] (Received 21 September 2014 ; accepted 10 December 2014 ) ISSN 2374-4235 print/ISSN 2374-4243 online © 2015 Informa Healthcare DOI: 10.3109/00365548.2014.1001998
Downloaded by [University of California, San Diego] at 00:54 14 September 2015
BAFF as a biomarker in HIV infection
Results Mean time of follow-up to the last registered visit was 109 months. Twelve of the 41 patients (29%) progressed to clinical AIDS. Mean time to development of AIDS was 32 months (interval, 1–82 months). Mean serum concentrations of BAFF were significantly higher in patients who later developed AIDS (2722 2197 vs 1905 1542 pg/mL, p 0.021). When we used the 75th percentile value of BAFF as a cut-off (2100 pg/mL), patients with higher concentrations (n 10) were at greater risk of developing AIDS (Cox regression: relative hazard [RH], 5.69; 95% confidence interval [CI], 1.79–18.15; p 0.0033). AIDS developed within the first 24 months of follow-up among HIV individuals with baseline BAFF 2100 pg/mL, while the first clinical AIDS occurred after the first 24 months in patients with lower BAFF levels (Figure 1). The lowest serum BAFF concentration (646 pg/mL) was observed in a patient who fulfilled criteria as HIV elite controller. Clinical variables that were associated with the risk for development of AIDS are presented in Table I. Regarding antiretroviral therapy, at the time of inclusion 26 patients were taking ART (n 19) or HAART (n 7). Eleven of these patients developed AIDS, seven on failing therapy. Five patients developed clinical AIDS before the introduction of HAART and two patients after HAART therapy was started. These two patients were found to have low CD4 counts (243 and 256 cells/uL), high CD8 CD38 ( 70%) and CD4 CD38 DR ( 14%) percentages and were not able to suppress viral replication. Five patients developed AIDS while on ART (four of these patients failed to control HIV viremia). Eleven patients had
Development of AIDS 1.0
.8 Cumulated Hazard
(Beckman, CA, USA); beta-2-microglobulin and neopterin were measured by radioimmunoassay (Pharmacia Diagnostics, Uppsala, Sweden and Immuno Biological, Hamburg, Germany, respectively). We selected the 75th percentile value as the cutoff point of biomarkers. Commonly used cut-off points were selected for CD4 and HIV viral load. Treatment failure was defined as a HIV viral load greater than 5000 copies/mL. Measurement of the degree of linear dependence between two variables was evaluated by Pearson correlation test. Proportional hazards models (Cox regression analysis) were performed to assess the relationship between BAFF levels and clinical outcome. Time to the onset of first clinical AIDS or latest available follow-up date were registered. The study was approved by the local ethical committee. A patient’s informed consent was obtained before examination and to perform further analysis of stored serum samples.
261
Log Rank 10.80 p= 0.001
.6 BAFF .4
> 2100 pg/mL
.2 < 2100 pg/mL 0.0 0
12 24 36 48 60 72 84 96 Time after study (months)
Figure 1. Kaplan-Meier curves shows that HIV patients with higher serum BAFF concentrations ( 2100 pg/mL) are correlated with more rapid progression into AIDS.
suppressed virus after HAART introduction. None of these patients developed AIDS. BAFF concentration and failing antiretroviral therapy at the time of inclusion remained significant risk factors for AIDS (RH, 5.02; 95% CI, 1.21–20.85; p 0.026 and RH, 5.77; 95% CI 1.51–21.90, p 0.01, respectively) in multivariate Cox regression analysis including serum BAFF, failing therapy at the time of inclusion, candidiasis, HIV status and time of HIV infection in the regression model. The risk for development of AIDS associated with BAFF concentration decreased after adjustment for absolute CD4 counts ( 350 cells/uL [RH, 3.36; 95% CI, 0.96–11.81; p 0.058]). BAFF levels remained a significant risk factor for development of AIDS after adjustment for viral load ( 400 copies/mL [RH, 4.20; 95% CI, 1.23–14.33; p 0.0219]). Moderately significant positive correlations were observed between BAFF levels and percentages of the following subsets: activated CD8 CD38 cells (Spearman coefficient, R 0.58; p 0.001); memoryactivated CD8 CD45RO CD38 (R 0.53, p 0.005); and activated CD4 CD38 DR (R 0.41, p 0.016). Interestingly, serum BAFF concentrations were not correlated with IgA serum levels (R –0.13, p 0.43), but were significantly associated with serum beta-2-microglobulin levels (R 0.52, p 0.002) and with neopterin concentrations (R 0.447, p 0.008). Discussion As we previously demonstrated for serum immunoglobulin levels [1] and CD4 and CD8 activated subsets [2], higher serum BAFF levels were an independent risk factor for development of AIDS.
262
J. Carbone et al.
Downloaded by [University of California, San Diego] at 00:54 14 September 2015
Table I. Univariate Cox regression analysis for factors associated with risk of first clinical AIDS. Characteristics*
N
Age 34 years (mean value) Time after HIV infection 7 years (mean value) Gender (male vs female) Anti-HCV positive Anti-HBV positive HIV CDC category B vs A Candidiasis (oral or vaginal)† Bacterial pneumonia (single episode)† Herpes zoster† Taking ART Taking HAART† ART/HAART failing patients‡ Serum BAFF 2100 pg/mL (75th p) CD4 350 cells/uL Viral load 400 copies/mL CD4 CD38 DR 17% (75th p) CD8 CD38 83% (75th p) Serum IgA 292 mg/dL (75th p) Neopterin 3.42 mg/L (75th p) Beta-2-microglobulin 3.95 mg/L (75th p)
21 22 33 34 23 24 11 13 9 19 18 7 10 18 17 10 10 10 10 10
Univariate HR (95% CI) 1.36 3.23 1.16 2.42 1.76 4.11 6.47 1.84 2.32 3.17 1.92 6.55 5.69 5.41 4.19 24.96 10.04 2.79 5.54 3.34
(0.43–4.30) (0.87–11.97) (0.31–4.30) (0.31–18.75) (0.53–5.84) (0.89–18.79) (2.02–20.76) (0.58–5.82) (0.69–7.83) (0.41–24.55) (0.61–6.07) (1.89–22.71) (1.79–18.15) (1.46–20.12) (1.25–14.01) (4.7–132.4) (2.36–48.81) (0.88–8.81) (1.73–17.55) (0.98–11.30)
p 0.59 0.079 0.82 0.398 0.359 0.068 0.0017 0.29 0.17 0.27 0.27 0.0030 0.0033 0.012 0.02 0.0002 0.0018 0.07 0.0039 0.052
ART, antiretroviral therapy; HAART, highly active antiretroviral therapy; HR, hazard ratio; N, number of events; 75th p, 75th percentile. *Clinical characteristics at the time or before the sample collection. †Clinical characteristics during follow-up. ‡Patients on failing therapy at the time of inclusion.
Previous studies have shown that serum BAFF levels were significantly higher among HIV-infected patients than among controls [3,4]. Rodriguez et al. [3] described higher BAFF concentrations among HIV-positive patients with lower CD4 cell counts. We are not aware of previous reports demonstrating that higher BAFF concentrations were associated with higher activated CD8 and CD4 T-cell percentages in HIV-infected individuals. BAFF activity has been observed in effector/memory T-cells (both CD8 and CD4 subsets), indicating that BAFF has a role in T-cell activation [5]. Previous studies have also evaluated the relationship between BAFF levels and other immune cell subtypes in HIV infection. In our study we found a significant correlation between serum BAFF and neopterin levels which is a monocyte activation factor. Our data suggest that a higher BAFF serum concentration might reflect better the increased immune activation status in HIV patients as this factor acts on distinct immune cells including T-cells, B-cells, and dendritic cells. Our new data are limited in their precision due to the small sample size but support the hypothesis that higher BAFF concentrations are associated with risk for development of AIDS. The retrospective analysis of the relationship between BAFF levels and clinical outcome was another limitation of our study. However, our observations and those obtained in previous studies suggest that serum BAFF is a good
candidate for further evaluation as a nonspecific surrogate marker in HIV infection in a replicating study performed in patients using current antiretroviral regimens. Declaration of interest: The authors report no conflicts of interest. The authors have no funding to report. The authors alone are responsible for the content and writing of the paper.
References [1] Carbone J, Sarmiento E, Rodriguez-Molina JJ, Gil J, Fernandez-Cruz E. Immunoglobulin levels and prediction of progression to AIDS in HIV-infected injection drug users. AIDS Patient Care STDS. 2004;18:685–6. [2] Carbone J, Gil J, Benito JM, Navarro J, Muñóz-Fernández A, Bartolomé J, et al. Increased levels of activated subsets of CD4 T cells add to the prognostic value of low CD4 T cell counts in a cohort of HIV-infected drug users. AIDS 2000;14:2823–9. [3] Rodriguez B, Valdez H, Freimuth W, Butler T, Asaad R, Lederman M. Plasma levels of B- lymphocyte stimulator increase with HIV disease progression. AIDS 2003;17: 1983–2000. [4] Fontaine J, Chagnon-Choquet J, Valcke HS, Poudrier J, Roger M. High expression levels of B lymphocyte stimulator (BLyS) by dendritic cells correlate with HIV-related B-cell disease progression in humans. Blood 2011;117:145–55. [5] Huard B, Schneider P, Mauri D, Tschopp J, French LE. T cell costimulation by the TNF ligand BAFF. J Immunol 2001; 167:6225–31.
