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1.
Afr Health Sci ; 18(4): 1066-1075, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30766573

ABSTRACT

BACKGROUND: E-selectin has been shown to play a role in atherosclerosis and to be increased in HIV-infected individuals due to chronic immune activation. There is a paucity of studies on E-selectin in HIV-infected treatment-naïve individuals. OBJECTIVES: This study aimed to determine whether E-selectin levels were increased in HIV-infected treatment-naïve individuals and whether these correlated with markers of disease severity, inflammation and coagulation to determine if this population is at risk for cardiovascular disease (CVD). METHODS: E-selectin levels were determined in 114 HIV-infected treatment-naive and 66 HIV-negative individuals, compared between groups and correlated with markers of disease severity, inflammation and coagulation. RESULTS: There were statistically significant differences (p<0.01) in levels of WCC, CD4+ count, %CD38/8, albumin, IgG, hsCRP and D-dimer between groups and no statistically significant differences in E-selectin (p=0.84) and fibrinogen (p=0.65) levels. E-selectin correlated with age (p=0.02) and gender (p=0.01). CONCLUSION: E-selectin was a poor marker in this setting. There was no correlation with any of the markers of disease severity, inflammation and coagulation. E-selectin is most likely raised in an acute inflammatory setting, rather than chronic stage of HIV-infection. We recommend that other markers be utilized to identify patients at increased risk of CVD; as these were significantly increased untreated in individuals.


Subject(s)
Blood Coagulation/physiology , E-Selectin/blood , HIV Infections/blood , Inflammation/metabolism , ADP-ribosyl Cyclase 1/metabolism , Adult , Atherosclerosis/blood , Biomarkers , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/analysis , HIV Infections/physiopathology , Humans , Inflammation Mediators/metabolism , Leukocyte Count , Male , Severity of Illness Index
2.
Clin Chem Lab Med ; 54(3): 501-8, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26485747

ABSTRACT

BACKGROUND: The chronic stage of human immunodeficiency virus (HIV) infection, although clinically asymptomatic, is characterized by activation of the immune system and persistent inflammation. Procalcitonin (PCT) has been studied in HIV infection as a marker of bacterial infection. Our aim was to assess the effect of persistent immune activation on PCT levels in asymptomatic treatment naïve HIV infected subjects. METHODS: This was a cross-sectional study of 68 asymptomatic antiretroviral therapy-naive HIV infected participants and 42 uninfected controls. Stored serum samples were used to measure: PCT, interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), high sensitivity C-reactive protein (hsCRP), immunoglobulin G (IgG) and albumin. PCT was correlated with markers of: disease progression (CD4 count and viral load), immune activation (CD 38 on CD8+ T cells, IgG and LBP), inflammation (IL-6, hsCRP and albumin). RESULTS: IL-6, IgG and CD8/38 were all significantly increased while albumin and CD4 counts were significantly lower in the HIV infected group. PCT levels were not significantly different between the two groups. There was no significant difference in LBP and hsCRP; however, their levels were increased in both groups. PCT correlated only with LBP (p=0.0001). IL-6 and LBP correlated positively with hsCRP and IgG. Albumin correlated inversely with IL-6 and viral load. Only IgG and CD8/38 correlated inversely with CD4 counts. CONCLUSIONS: We demonstrated the activation of the innate (raised LBP), humoral (raised IgG) and cellular immune systems (increased CD8/38 T cells). Despite a state of persistent inflammation, PCT levels are not elevated in asymptomatic untreated HIV infection.


Subject(s)
Asymptomatic Diseases , Biomarkers/blood , Calcitonin/therapeutic use , HIV Infections/drug therapy , Adult , Antiretroviral Therapy, Highly Active , C-Reactive Protein/chemistry , C-Reactive Protein/immunology , Cohort Studies , Cross-Sectional Studies , Disease Progression , Female , Humans , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , Receptors, Calcitonin/therapeutic use , South Africa
3.
South Afr J HIV Med ; 17(1): 445, 2016.
Article in English | MEDLINE | ID: mdl-29568606

ABSTRACT

BACKGROUND: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIV-positive treatment-naive individuals has thus far not been investigated. AIMS AND OBJECTIVES: To optimise a five-colour flow cytometric assay for measurement of thymic function by measuring recent thymic emigrants (RTEs) in treatment-naive HIV-infected patients and healthy controls and correlate results with levels of immune activation, CD4 counts and viral load. METHODS: Blood obtained from 53 consenting HIV-positive individuals and 32 controls recruited from HIV prevention and testing clinic in Cape Town, South Africa. RTEs were measured (CD3+/CD4+/CD45RA+/CD31+/CD62L+) and levels were correlated with CD4 counts of HIV-infected individuals, log viral load and levels of immune activation (CD8+/CD38+ T-cells). RESULTS: HIV-infected individuals had reduced frequencies of RTEs when compared to controls (p = 0.0035). Levels of immune activation were inversely correlated with thymic function (p = 0.0403), and the thymic function in HIV-infected individuals showed no significant correlation with CD4 counts (p = 0.31559) and viral load (p = 0.20628). CONCLUSIONS: There was impaired thymic function in HIV-infected individuals, which was associated with increased levels of immune activation. The thymic dysfunction was not associated with CD4 counts and viral load. Immune activation may result in inflammatory damage to the thymus and subsequent thymic dysfunction, and CD4 counts and viral load may not necessarily reflect thymic dysfunction in HIV.

4.
Thromb Res ; 135(6): 1131-9, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25900311

ABSTRACT

INTRODUCTION: Human immunodeficiency virus (HIV) induces inflammation and platelet activation. People living with HIV are at increased risk of thrombotic events. Activated platelets link inflammation with thrombosis. However platelet function in HIV remains unclear. P-selectin (CD62P), a marker of platelet activation, and platelet glycoprotein GPIV (CD36) a marker of platelet aggregation, can be measured using flow cytometry. We raise a hypothesis that HIV alters the signalling pathways involved in normal platelet function. We evaluated platelet function in HIV using a whole blood platelet flow cytometry based assay. MATERIALS AND METHODS: Fifty-eight antiretroviral therapy naïve HIV infected and 38 HIV negative individuals were recruited in a clinic in Cape Town. Platelet surface CD36 and CD62P were measured using flow cytometry. These were then correlated with CD4 count, viral load and %CD38 on CD8+ T-cells. Platelet function was evaluated using adenosine diphosphate, arachidonic acid and collagen at varying concentrations. RESULTS: The HIV group showed increased levels of %CD62P (median 5.51[3.03- 10.11] vs. Control group 2.14[0.19 - 3.59], p<0.0001. This correlated with Viral load (r=0.336, P=0.008). The HIV group also showed increased levels of platelet %CD36 21.93[11.03-44.92] vs. Control 16.15[2.24-25.37], p=0.0087) which correlated with viral load (r=0.398, p=0.024). The HIV group showed a hyper response to AA and collagen at various concentrations. Notably, the HIV group only showed a hyper response to ADP at a maximal concentration of 20 µM (median CD62P MFI, 1.91[1.64-4.95] vs. Control 1.75[1.45-2.44] p=0.0279. CONCLUSION: The measurement of platelet function using flow cytometry is a rapid technique for the evaluation of platelet signalling pathways that may be modified in HIV infected individuals.


Subject(s)
Flow Cytometry/methods , HIV Infections/blood , Platelet Function Tests/methods , Adult , Blood Platelets/virology , CD36 Antigens/blood , Cohort Studies , Collagen/chemistry , Cross-Sectional Studies , Disease Progression , Female , HIV Infections/immunology , Humans , Male , P-Selectin/blood , Platelet Activation , Platelet Aggregation , RNA, Viral/analysis , Signal Transduction
5.
J Thromb Thrombolysis ; 40(4): 458-67, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25899563

ABSTRACT

Platelet aggregates play a crucial role in the immune defence mechanism against viruses. Increased levels of lipopolysaccharide have been reported in human immunodeficiency virus (HIV) infected individuals. Platelets are capable of interacting with bacterial LPS and subsequently forming platelet leukocyte aggregates (PLAs). This study aimed at determining the levels of circulating PLAs in treatment naïve HIV infected individuals and correlating them, with markers of immune activation, disease progression and platelet aggregation. Thirty-two HIV negative and 35 HIV positive individuals were recruited from a clinic in the Western Cape. Platelet monocyte and platelet neutrophil aggregates were measured using flow cytometry at baseline and were correlated with markers of platelet activation (CD62P); aggregation (CD36); monocyte and neutrophil activation (CD69); monocyte tissue factor expression (CD142); immune activation (CD38 on T+ cells); D-dimers (a marker of active coagulation); CD4 count and viral load. Platelet monocyte aggregates were also measured post stimulation with lipopolysaccharide. PMA levels were higher in HIV 25.26 (16.16-32.28) versus control 14.12 (8.36-18.83), p = 0.0001. PMAs correlated with %CD38/8 expression (r = 0.54624, p = 0.0155); CD4 count (r = -0.6964, p = 0.0039) viral load (r = 0.633, p < 0.009) and monocyte %CD69 expression (r = 0.757, p = 0.030). In addition the %PMAs correlated with platelet %CD36 (r = 0.606, p = 0.017). The HIV group showed increased levels of %CD62P 5.44 (2.72-11.87) versus control 1.15 (0.19-3.59), p < 0.0001; %CD36 22.53 (10.59-55.15) versus 11.01 (3.69-26.98), p = 0.0312 and tissue factor (CD142) MFI 4.84 (4.01-8.17) versus 1.74 (1.07-9.3), p = 0.0240. We describe increased levels of circulating PMAs which directly correlates with markers of immune activation, disease progression and platelet aggregation in HIV treatment naïve individuals.


Subject(s)
Blood Platelets/immunology , HIV Infections/immunology , HIV-1/immunology , Leukocytes/immunology , Platelet Aggregation/immunology , Adult , Biomarkers/blood , Blood Platelets/metabolism , Blood Platelets/pathology , Female , HIV Infections/blood , Humans , Leukocytes/metabolism , Leukocytes/pathology , Male
6.
J Clin Pathol ; 68(2): 148-53, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25452398

ABSTRACT

AIM: Serum free light chain measurements are used to follow-up and manage patients with monoclonal gammopathies, and abnormal ratios are associated with risk of progression in certain diseases. B cell dysfunction is well described in HIV and patients are at risk of developing B cell lymphomas. This study investigated whether HIV is associated with abnormal free light chain levels and the impact of antiretroviral treatment (ART) on these. METHODS: κ And λ free light chain concentrations and ratios, serum albumin and immunoglobulin G (IgG) were measured in 366 HIV positive subjects and correlated with CD4+ counts, viral loads, IgG, albumin and ART use. RESULTS: 66% were women and most were black Africans (66%), 26% were of mixed ethnicity and 8% were Caucasian or of unknown or other race. 89% were on ART. κ Free light chain values ranged from 5.59 to 357.0 mg/L (median 19.6 mg/L) and λ free light chain values ranged from 9.28 to 286 mg/L (median 22.3 mg/L). Both correlated positively with viral load and IgG and negatively with CD4+ counts and albumin concentrations. The ratio only correlated with IgG concentrations. Patients on ART had significantly lower free light chain concentrations, but the ratio was not significantly affected. CONCLUSIONS: This study demonstrated that free light chain concentrations were significantly correlated with markers of HIV disease severity, suggesting ongoing B cell dysfunction despite ART use. Free light chain ratio was not significantly affected.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/immunology , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Adolescent , Adult , Aged , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/virology , Biomarkers/blood , CD4 Lymphocyte Count , Female , HIV Infections/blood , HIV Infections/diagnosis , Humans , Immunoglobulin G/blood , Male , Middle Aged , Predictive Value of Tests , Serum Albumin/analysis , Serum Albumin, Human , Severity of Illness Index , South Africa , Treatment Outcome , Viral Load , Young Adult
7.
Ann Clin Biochem ; 52(Pt 3): 346-51, 2015 May.
Article in English | MEDLINE | ID: mdl-25487599

ABSTRACT

BACKGROUND: B lymphocyte stimulation is described in human immunodeficiency virus (HIV) infection and results in ongoing immunoglobulin production with abnormal serum protein electrophoresis patterns. We hypothesized that serum protein electrophoresis patterns would be abnormal in untreated HIV subjects and correlate with markers of disease severity. METHODS: Serum protein electrophoresis was performed on 70 HIV-positive, clinically well treatment-naïve subjects and 42 HIV-negative controls and correlated with markers of disease severity, namely CD4+ counts, viral loads, IgG and albumin. RESULTS: The mean age for both groups was 33 years, and female-to-male ratios were 4:1. All were of Black ethnicity. Mean CD4 counts ± SD for HIV group and controls were 419.5 ± 218.6 and 960.4 ± 378.5 cells/mm(3), respectively. Of the HIV-infected group, 44% showed polyclonal hypergammaglobulinaemia versus 10% of controls (P < 0.01). The HIV group had 27% with an abnormal pattern requiring immunofixation which revealed nine (12.5% of total) had oligoclonal bands, seven (10.3% of total) had polyclonal hypergammaglobulinaemia and three (4% of total) had monoclonal bands. CD4+ counts were lower in those with polyclonal hypergammaglobulinaemia or abnormal serum protein electrophoresis. Interestingly, viral load results showed no statistically significant differences. CONCLUSION: We found a remarkably high level (53%) of polyclonal hypergammaglobulinaemia in our untreated population compared with uninfected controls (10%). Only 4% of the HIV-positive group had a monoclonal band. Polyclonal hypergammaglobulinaemia correlated significantly with lower CD4+ counts. These results highlight the generalized B cell stimulation in untreated HIV infection. Future longitudinal studies will be important to determine the prognostic value of these findings.


Subject(s)
Anti-Retroviral Agents , CD4 Antigens/blood , Electrophoresis/methods , HIV Infections/blood , gamma-Globulins/analysis , Adult , Cross-Sectional Studies , Female , HIV Infections/diagnosis , Humans , Male , Middle Aged , Retrospective Studies , Viral Load/methods , Young Adult
8.
Platelets ; 26(3): 250-7, 2015.
Article in English | MEDLINE | ID: mdl-24831969

ABSTRACT

Human immunodeficiency deficiency virus (HIV) infection is associated with chronic inflammation and an increased risk of thrombotic events. Activated platelets (PLTs) play an important role in both thrombosis and inflammation, and HIV has been shown to induce PLT activation by both direct and indirect mechanisms. P-selectin (CD62P) is a well-described marker of PLT activation, and PLT glycoprotein (GP) IV (CD36) has been identified as a marker of PLT aggregation. Data on PLT function in the context of HIV infection remain inconclusive. Laboratory techniques, such as flow cytometry, enable the assessment of PLTs in their physiological state and environment, with minimal artifactual in vitro activation and aggregation. In this study, we describe a novel flow cytometry PLT assay, which enabled the measurement of PLT function in HIV infection. Forty-one antiretroviral-naïve HIV-positive individuals and 41 HIV-negative controls were recruited from a clinic in the Western Cape. Platelet function was evaluated by assessing the response of platelets to adenosine diphosphate (ADP) at two concentrations (0.04 mM, 0.2 mM). The percentage expression and mean fluorescence intensity (MFI) of CD62P and CD36 was used to evaluate platelet function. These were then correlated with platelet (PLT) count; CD4 count; % CD38/8; viral load and D-dimers. The % CD62P levels were higher in HIV-positive patients (HIV % CD62P 11.33[5.96-29.36] vs. control 2.48[1.56-6.04]; p < 0.0001). In addition, the HIV group showed higher CD62P MFI levels (HIV CD62P MFI 3.25 ± 7.23 vs. control 2.35 ± 1.31, p = 0.0292). Baseline levels of %CD36 expression were significantly higher in HIV-positive patients (%CD36 12.41[6.31-21.83] vs. control 6.04[1.34-13.15]; p = 0.0091). However, the baseline CD36MFI showed no significant difference between the two groups (HIV CD36 MFI 3.09 ± 0.64 vs. control 2.44 ± 0.11, p = 0.4591). The HIV group showed higher levels of % CD36 expression post stimulation with 0.04 mM ADP 43.32 ± 27.41 vs. control 27.47 ± 12.95; p < 0.0214) and no significant difference at 0.2 mM ADP (HIV % CD36 39.06 ± 17.91 vs. control 44.61 ± 18.76; p = 0.3277). Furthermore, the HIV group showed a single phase response to ADP as compared to the control group, which showed a normal biphasic response. We concluded that PLT flow cytometry is valuable in the assessment of levels of PLT activation, and further, that the addition of an endogenous agonist, such as ADP, enabled the measurement of PLT function in HIV infection. We were able to show that, although PLTs are significantly activated in HIV compared to uninfected controls, they retain their functional capacity.


Subject(s)
Blood Platelets/metabolism , HIV Infections/metabolism , Platelet Activation , Platelet Aggregation , Adenosine Diphosphate/pharmacology , Adult , Antigens, Surface/metabolism , Blood Platelets/drug effects , CD4 Lymphocyte Count , Case-Control Studies , Female , Flow Cytometry , HIV Infections/blood , HIV Infections/immunology , HIV Infections/virology , Humans , Immunophenotyping , Male , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Platelet Count , Viral Load , Young Adult
9.
Crit Rev Clin Lab Sci ; 51(2): 98-111, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24479745

ABSTRACT

Inflammation and immune activation have been thrust to center stage in the understanding of HIV-1 disease pathogenesis and progression. Early work demonstrated that heightened levels of immune activation correlated with the extent of CD4 + T cell death in lymphoid tissue; however, this concept was not incorporated into the general view of disease pathogenesis. Since these early studies, the extension of life for patients on combination antiretroviral therapies (cART) has heralded a new era of non-AIDS-related diseases and incomplete restoration of immune function. The common link appears to be ongoing inflammation and immune activation. Thus, despite good control of viral loads, persons living with HIV (PLWH) remain at increased risk of inflammatory-associated complications such as cardiovascular disease and certain cancers. HIV-specific mechanisms as well as non-specific generalized responses to infection contribute to ongoing activation of the immune system. An early loss of gastrointestinal (GI) tract mucosal integrity, the pro-inflammatory cytokine milieu, co-infections and marked destruction of lymph node architecture are all factors contributing to the ongoing activation of the immune system as well as impaired immune recovery. It is becoming increasingly evident that the CD4 count and viral load do not provide a complete picture of the underlying state of the immune system. Heightened levels of inflammatory markers have been shown to predict increased mortality and other adverse events. Therefore, it will be important to incorporate these markers into management algorithms as soon as possible. This is particularly relevant in resource-poor countries where difficulties in cART roll-out and access are still encountered and, therefore, a mechanism for prioritizing individuals for therapy would be of value. This review will focus on the closely inter-related concepts of immune activation and inflammation. Both are broad concepts involving the interaction of various key players in the immune system. Importantly, immune activation promotes inflammation and thrombosis and similarly, inflammation and thrombosis induce immune activation. These concepts are thus intricately linked. Studies highlighting the potentially harmful effects of ongoing inflammation/immune activation are reviewed and the contributions of the GI tract "damage" and other co-infections such as CMV are explored. The complications resulting from persistent immune activation include enhanced CD4 + T cell death, lymphoid tissue destruction, and various pathologies related to chronic inflammation. Ultimately, we envision that the long-term management of the disease will incorporate both the identification and the amelioration of the potentially harmful effects of ongoing immune activation and inflammation.


Subject(s)
HIV Infections , HIV-1 , Inflammation , Disease Progression , HIV Infections/diagnosis , HIV Infections/immunology , HIV Infections/physiopathology , Humans , Prognosis
10.
Immunol Res ; 60(1): 11-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24469917

ABSTRACT

Immune activation is a strong predictor of disease outcome in HIV infection and promotes the loss of CD4+ T cells. The neuropeptide, vasoactive intestinal peptide (VIP), has immune-modulating properties with specific receptors identified on lymphocytes; VPAC1 and VPAC2. Studies have shown that VIP limits immune activation and apoptosis in T cells by decreasing the expression of the apoptosis signaling molecule Fas ligand (FasL). VIP receptor surface expression has not been investigated by flow cytometry in the context of HIV infection and may represent a novel target for immune-modulating therapy. Eighty-seven untreated HIV-infected individuals with CD4 counts >200 and 57 uninfected controls were recruited from a primary health clinic in Cape Town, South Africa. Flow cytometry was used to determine levels of expression of VPAC1 and VPAC2, as well as FasL on CD4+ T cells, and these results were correlated with the immune activation phenotype %CD38+CD8+ T cells. VPAC2 expression was significantly increased in the HIV group (mean %VPAC2+CD4+ cells 19.25 vs. control 12.56; p ≤ 0.0001), but no difference in VPAC1 expression was observed. VPAC2 correlated positively with FasL (r = 0.310; p = 0.001), and there was a significant inverse correlation between FasL and the CD4 count (r = -0.211; p = 0.013) and a direct correlation with %CD38+CD8+ T cells (r = 0.39; p ≤ 0.0001). Thus, higher levels of immune activation correlated with higher levels of the death-signaling FasL and lower CD4 counts. VPAC2 may provide a novel target for the selective limitation of CD4+ T-cell death in HIV infection.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Fas Ligand Protein/immunology , HIV Infections/immunology , Receptors, Vasoactive Intestinal Peptide, Type II/immunology , ADP-ribosyl Cyclase 1/immunology , Adult , Female , Humans , Male , Middle Aged , Receptors, Vasoactive Intestinal Polypeptide, Type I/immunology , Young Adult
11.
Ann Clin Biochem ; 51(Pt 5): 568-75, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24142400

ABSTRACT

BACKGROUND: As lifespan in HIV infection increases, cardiovascular disease has emerged as a cause of morbidity and mortality. Asymmetric dimethylarginine is an established marker of endothelial dysfunction and predicts cardiovascular events. The role of asymmetric dimethylarginine in HIV-related cardiovascular disease has not been established. Our aim was to determine whether asymmetric dimethylarginine concentrations were elevated in treatment naïve, HIV-infected subjects and to correlate these with markers of immune activation and disease progression. METHODS: Serum samples were collected from HIV-positive and -negative subjects attending a primary health care clinic over a 12-month period. Asymmetric dimethylarginine concentrations were measured and correlated with CD4 count, viral load, hsCRP, IL-6, IgG, adenosine deaminase and CD8/38 T lymphocytes. RESULTS: Sixty HIV-positive participants (mean age 32.0 years) and 20 HIV-negative controls (mean age 32.4 years) were studied. All were of black ethnicity. The mean asymmetric dimethylarginine concentration in the infected group measured 0.67 µmol/L (95% CI 0.62-0.72 µmol/L) which was significantly higher than in the control group of 0.48 µmol/L (95% CI 0.40-0.56 µmol/L). Asymmetric dimethylarginine correlated inversely with CD4 counts and positively with IgG, adenosine deaminase and CD8/38 T lymphocytes. No significant correlation was found with hsCRP, IL-6, or viral load. CONCLUSION: We demonstrated that asymmetric dimethylarginine is elevated in HIV infection, in patients with relatively well-preserved CD4 counts not yet on anti-retroviral treatment. We showed significant correlations of asymmetric dimethylarginine with CD8/38 T lymphocytes, IgG and adenosine deaminase, suggesting that T-cell activation and the adaptive immune response underlie asymmetric dimethylarginine elevation in this population.


Subject(s)
Arginine/analogs & derivatives , Biomarkers/blood , Cardiovascular Diseases/blood , HIV Infections/blood , Adenosine Deaminase/blood , Adult , Arginine/blood , Arginine/immunology , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , Cardiovascular Diseases/etiology , Case-Control Studies , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/immunology , HIV Seropositivity , Humans , Immunoglobulin G/blood , Interleukin-6/blood , Male , Viral Load
12.
Acta Haematol ; 131(4): 208-12, 2014.
Article in English | MEDLINE | ID: mdl-24296523

ABSTRACT

INTRODUCTION: Chronic immune activation is associated with the accelerated progression of HIV to AIDS; however, affordable markers reflecting this have not yet been determined. The percentage of large unstained cells (%LUCs) is a differential count parameter measured by certain routine hematology analyzers and reflects activated lymphocytes and peroxidase-negative cells. We hypothesized that the %LUCs would be increased in HIV infection and would correlate with markers of immune activation [i.e. CD38 expression on CD8+ T cells (%CD38onCD8) and lipopolysaccharide-binding protein (LBP)] and CD4 counts. METHODS: In this cross-sectional study, 78 HIV-infected, antiretroviral therapy-naïve adults and 52 uninfected controls were recruited. %CD38onCD8 and CD4 counts were determined by flow cytometry, LBP levels were assessed by immunoassay, and the %LUCs was tested on a Siemens ADVIA 2120. RESULTS: Significant differences were found between the HIV-infected and control groups for %LUCs (95% CI 2.3-2.7 vs. 1.8-2.2, respectively; p = 0.001), as well as for %CD38onCD8, LBP, and CD4 counts. Furthermore, %LUCs correlated directly with %CD38onCD8 and LBP and inversely with CD4 counts. CONCLUSION: The %LUCs was significantly increased in this untreated, asymptomatic, HIV-infected group and correlated with markers of immune activation and CD4 counts. Therefore, the %LUCs may be of value in identifying HIV-infected patients at risk of accelerated disease progression.


Subject(s)
HIV Infections/pathology , Lymphocyte Activation , Lymphocytes/pathology , Acute-Phase Proteins/metabolism , Adult , Biomarkers/blood , Black People , CD4 Lymphocyte Count , Carrier Proteins/blood , Carrier Proteins/metabolism , Cell Size , Cohort Studies , Cross-Sectional Studies , Disease Progression , Female , HIV Infections/immunology , HIV Infections/physiopathology , HIV Infections/virology , HIV-1/immunology , HIV-1/isolation & purification , HIV-1/metabolism , Humans , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/virology , Male , Mass Screening , Membrane Glycoproteins/blood , Membrane Glycoproteins/metabolism , RNA, Viral/blood , RNA, Viral/metabolism , South Africa , Viral Load
13.
J Clin Pathol ; 66(11): 992-5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23801498

ABSTRACT

Monoclonal serum free light chain measurements are used to follow up and manage patients with monoclonal gammopathies, and abnormal serum free light chain ratios are associated with risk of progression in certain diseases. We aimed to validate the reference intervals in our population. Reference intervals for κ and λ free light chains were established on 120 healthy adults. Creatinine levels were measured to exclude renal dysfunction and serum protein electrophoresis was performed. All creatinine values were within normal limits. After exclusion of subjects with abnormal serum protein electrophoreses, 113 subjects were available for analysis. The 95% reference interval was 6.3-20.6 mg/L for κ free light chains, 8.7-25.9 mg/L for λ free light chains and 0.46-1.23 for free light chain ratio. Most of the values fell within the manufacturer's recommended limits and therefore could be used for our population.


Subject(s)
Antibodies, Monoclonal/immunology , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Paraproteinemias/blood , Adult , Creatinine/blood , Female , Humans , Male , Middle Aged , Reference Values , Serum/immunology , South Africa , Young Adult
14.
Clin Chim Acta ; 416: 96-9, 2013 Feb 01.
Article in English | MEDLINE | ID: mdl-23228847

ABSTRACT

HIV-infection is associated with ongoing activation of the immune system and persistent inflammation. These are key driving forces in the loss of CD4+ T cells, progression to AIDS and development of non-HIV-related complications such as cardiovascular disease and certain cancers. Diseases associated with accelerated aging are increasing in incidence despite good anti-retroviral therapy (ART). The common underlying mechanism appears to be chronic inflammation. HIV-specific mechanisms as well as non-specific generalized responses to infection contribute to the chronic and aberrant activation of the immune system. An early loss of gut mucosal integrity, the pro-inflammatory cytokine milieu, co-infections and later, marked destruction of lymph node architecture are all factors contributing to the ongoing activation of both the innate and adaptive immune systems. These factors paradoxically promote CD4+ T cell loss, both by providing additional substrate for viral infection in the form of activated CD4+ T cells, as well as by priming non-infected 'bystander' CD4+ T cells for death by apoptosis. However, the relative contributions of each of these mechanisms to ongoing immune activation remain to be determined. Cost-effective markers of inflammation and selective anti-inflammatory agents are important fields of current and future research.


Subject(s)
CD4 Antigens/blood , HIV Infections/immunology , HIV Infections/pathology , Disease Progression , Humans , Inflammation/pathology
15.
J Clin Immunol ; 33(3): 605-12, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23160984

ABSTRACT

PURPOSE: HIV-infection is characterized by aberrant immune activation and ongoing inflammation. Markers of inflammation are now recognized to have prognostic value for adverse events, independent of viral loads and CD4 counts. This study aimed to delineate a panel of affordable markers of immune activation in untreated HIV-infection that may have an impact on the management of HIV in resource-limited settings. METHODS: This was a cross-sectional study of 86 untreated newly diagnosed HIV-infected patients and 54 matched controls attending a voluntary testing clinic in Cape Town, South Africa. Serum levels of adenosine deaminase (ADA), total immunoglobulin G (IgG), soluble CD14 and lipopolysaccharide-binding protein (LBP) were measured and correlated with CD4 counts, viral loads and expression of CD38 on CD8+ T cells. RESULTS: ADA, IgG and LBP were all significantly increased in the HIV infected group (p < 0.0001) compared with uninfected controls. Soluble CD14 was also significantly increased (p = 0.0187). Furthermore, all these parameters correlated inversely with CD4 counts (r = -0.481 p < 0.0001; r = -0.561; p < 0.0001; r = -0.387 p = 0.0007 and r = -0.254 p = 0.0240, respectively). Only ADA correlated with viral load (r = 0.260 p = 0.0172). Importantly, ADA, IgG and LBP correlated directly with %CD38 on CD8+ T cells (r = 0.369 p < 0.0001; r = 0.284 p = 0.001; r = 0.408 p = 0.0006, respectively). CONCLUSION: Affordable parameters such as serum ADA and IgG correlated significantly with immune activation levels and markers of disease progression in untreated HIV-infection and therefore may add value to the management of these patients in resource-limited settings.


Subject(s)
Adenosine Deaminase/blood , CD4-Positive T-Lymphocytes/immunology , HIV Infections/blood , HIV Infections/immunology , Immunoglobulin G/blood , Adult , Biomarkers/blood , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , Female , HIV Infections/drug therapy , HIV-1/immunology , Humans , Immunoglobulin G/immunology , Lymphocyte Activation , Male , Middle Aged , Viral Load , Young Adult
16.
S Afr Med J ; 104(1): 45-8, 2013 Oct 11.
Article in English | MEDLINE | ID: mdl-24388088

ABSTRACT

BACKGROUND: A feature of HIV/AIDS is chronic immune activation, which results in a number of complications including inflammation-related disorders and blood cytopaenias. Immune activation status is not routinely tested in HIV infection. However, the full blood count (FBC) is a commonly performed test. OBJECTIVE: We hypothesised that FBC parameters would be significantly different in HIV-infected v. -uninfected individuals, and that some of these parameters would correlate with markers of immune activation (i.e. percentage CD38 expression on CD8(+) T cells (%CD38onCD8)) and disease progression (i.e. CD4(+) counts) in HIV infection. METHODS: This was a cross-sectional study with 83 HIV-infected adults who were antiretroviral therapy-naive and clinically well, and 51 HIV-uninfected adults. The %CD38onCD8 and CD4(+) counts were determined by flow cytometry and the FBC was performed on a Siemens ADVIA 2120 system. FBC parameters investigated were total white cell count (WCC), haemoglobin (Hb) concentration, platelet count, absolute neutrophil count, absolute lymphocyte count, and percentage of large unstained cells (%LUCs). RESULTS: Significant differences were found between the HIV-infected and -uninfected groups for total WCC, Hb, neutrophil count, lymphocyte count and %LUCs. The mean ± standard deviation (SD) for the total WCC (5.3±1.3 v. 6.9±2.2; p≤0.001) and the %LUCs (2.5±0.9 v. 2.0±0.9; p=0.001) both showed correlations with CD4(+) counts and %CD38onCD8. CONCLUSION: The total WCC and %LUCs showed significant differences in HIV-infected individuals and correlated with markers of immune activation and disease progression. This suggests the potential use of these parameters as markers of immune activation in HIV infection.


Subject(s)
HIV Infections/immunology , Leukocyte Count , ADP-ribosyl Cyclase 1/analysis , Adult , CD4 Lymphocyte Count , CD8-Positive T-Lymphocytes/immunology , Cross-Sectional Studies , Female , Flow Cytometry , Humans , Male
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