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  1. A study of Malaysian drug addicts with human immunodeficiency virus infection
    Yoong KY, Cheong I
    Int J STD AIDS, 1997 Feb;8(2):118-23.
    PMID: 9061411
    A cross-sectional study was undertaken to determine the clinical profile, haematological and biochemical changes, seroprevalence of common opportunistic pathogens, and AIDS-defining events in 49 Malaysian male drug addicts with HIV infection. Their mean age was 33.2 years, the majority had been injecting drugs for more than 5 years and 88% reporting sharing needles. Fatigue, weight loss and night sweats were common presenting symptoms and the most frequent physical findings were hepatomegaly (57%), lymphadenopathy (35%) and thrush (29%). Pulmonary infections were the commonest complications seen (61%) and of these, 13 had septic pulmonary emboli, 7 had bacterial pneumonias, 7 had pulmonary tuberculosis, and 4 had Pneumocystis carinii pneumonia. Eight patients had infective endocarditis and 5 had infected pseudoaneurysm in the groin. Anaemia (82%), leucocytosis (53%), hypoalbuminaemia (43%), hyperglobulinaemia (88%), elevated liver enzymes and hyponatraemia (57%) were frequent laboratory findings. The prevalence of HCV, HBV, cytomegalovirus and toxoplasma infection (by serology) were 100%, 12.2%, 72.7% and 59% respectively. All 7 patients with AIDS (4 P. carinii pneumonia, 2 extrapulmonary tuberculosis, and one oesophageal candidiasis) presented with their AIDS-defining illness, suggesting that HIV-infected intravenous drug user (IVDU) patients present late in the course of the disease.
    Matched MeSH terms: CD4-CD8 Ratio
  2. Fulltext CD4/CD8 Ratio Recovery Among People Living With HIV Starting With First-Line Integrase Strand Transfer Inhibitors: A Prospective Regional Cohort Analysis
    Han WM, Avihingsanon A, Rajasuriar R, Tanuma J, Mundhe S, Lee MP, et al.
    J Acquir Immune Defic Syndr, 2023 Feb 01;92(2):180-188.
    PMID: 36625858 DOI: 10.1097/QAI.0000000000003121
    BACKGROUND: We evaluated trends in CD4/CD8 ratio among people living with HIV (PLWH) starting antiretroviral therapy (ART) with first-line integrase strand transfer inhibitors (INSTI) compared with non-INSTI-based ART, and the incidence of CD4/CD8 ratio normalization.

    METHODS: All PLWH enrolled in adult HIV cohorts of IeDEA Asia-Pacific who started with triple-ART with at least 1 CD4, CD8 (3-month window), and HIV-1 RNA measurement post-ART were included. CD4/CD8 ratio normalization was defined as a ratio ≥1. Longitudinal changes in CD4/CD8 ratio were analyzed by linear mixed model, the incidence of the normalization by Cox regression, and the differences in ratio recovery by group-based trajectory modeling.

    RESULTS: A total of 5529 PLWH were included; 80% male, median age 35 years (interquartile range [IQR], 29-43). First-line regimens were comprised of 65% NNRTI, 19% PI, and 16% INSTI. The baseline CD4/CD8 ratio was 0.19 (IQR, 0.09-0.33). PLWH starting with NNRTI- (P = 0.005) or PI-based ART (P = 0.030) had lower CD4/CD8 recovery over 5 years compared with INSTI. During 24,304 person-years of follow-up, 32% had CD4/CD8 ratio normalization. After adjusting for age, sex, baseline CD4, HIV-1 RNA, HCV, and year of ART initiation, PLWH started with INSTI had higher odds of achieving CD4/CD8 ratio normalization than NNRTI- (P < 0.001) or PI-based ART (P = 0.015). In group-based trajectory modeling analysis, INSTI was associated with greater odds of being in the higher ratio trajectory.

    CONCLUSIONS: INSTI use was associated with higher rates of CD4/CD8 ratio recovery and normalization in our cohort. These results emphasize the relative benefits of INSTI-based ART for immune restoration.

    Matched MeSH terms: CD4-CD8 Ratio
  3. Fulltext CD4:CD8 ratio comparison between cohorts of HIV-positive Asians and Caucasians upon commencement of antiretroviral therapy
    Petoumenos K, Choi JY, Hoy J, Kiertiburanakul S, Ng OT, Boyd M, et al.
    Antivir Ther, 2017;22(8):659-668.
    PMID: 28291735 DOI: 10.3851/IMP3155
    BACKGROUND: In the era of effective antiretroviral treatment (ART) CD4:CD8 ratio is proposed as a potential marker for HIV-positive (HIV+) patients at increased risk for non-AIDS comorbidities. The current study aims to compare CD4:CD8 ratio between Asian and Caucasian HIV+ patients.

    METHODS: HIV+ patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) meeting specific criteria were included. In these analyses Asian and Caucasian status were defined by cohort. Factors associated with a low CD4:CD8 ratio (cutoff <0.2) prior to ART commencement, and with achieving a normal CD4:CD8 ratio (>1) at 12 and 24 months post ART commencement were assessed using logistic regression.

    RESULTS: There were 591 patients from AHOD and 2,620 patients from TAHOD who met the inclusion criteria. TAHOD patients had a significantly (P<0.001) lower odds of having a baseline (prior to ART initiation) CD4:CD8 ratio greater than 0.2. After 12 months of ART, AHOD patients were more than twice as likely to achieve a normal CD4:CD8 ratio compared to TAHOD patients (15% versus 6%). However, after adjustment for confounding factors there was no significant difference between cohorts in the odds of achieving a CD4:CD8 ratio >1 (P=0.475).

    CONCLUSIONS: We found a significantly lower CD4:CD8 ratio prior to commencing ART in TAHOD compared to AHOD even after adjusting for confounders. However, after adjustment, there was no significant difference between the cohorts in odds of achieving normal ratio. Baseline CD4+ and CD8+ counts seem to be the main driver for this difference between these two populations.

    Matched MeSH terms: CD4-CD8 Ratio*
  4. Fulltext Impact of antiretroviral therapy (ART) timing on chronic immune activation/inflammation and end-organ damage
    Rajasuriar R, Wright E, Lewin SR
    Curr Opin HIV AIDS, 2015 Jan;10(1):35-42.
    PMID: 25415420 DOI: 10.1097/COH.0000000000000118
    The purpose of this review was to summarize recent studies on the effect of early antiretroviral therapy (ART) in HIV-infected patients on markers of immune activation/inflammation, viral persistence and serious non-AIDS events.
    Matched MeSH terms: CD4-CD8 Ratio
  5. Beta-2 microglobulin as an immunological marker to assess the progression of human immunodeficiency virus infected patients on highly active antiretroviral therapy
    Chitra P, Bakthavatsalam B, Palvannan T
    Clin Chim Acta, 2011 May 12;412(11-12):1151-4.
    PMID: 21300045 DOI: 10.1016/j.cca.2011.01.037
    Acquired immune deficiency syndrome (AIDS) defines the end stage of Human immunodeficiency viral (HIV) infection before the introduction of highly active antiretroviral therapy (HAART). This study was carried out to assess the serum β-2 microglobulin (B2M) as a marker for progression of HIV infected patients undergoing HAART.
    Matched MeSH terms: CD4-CD8 Ratio
  6. Disparity in the percentage of CD4+ T lymphocytes and prognosis of HIV-infected intravenous drug users in Malaysia
    Norazmi MN, Suarn S
    Immunol Lett, 1994 Dec;43(3):177-82.
    PMID: 7721330
    The CD4+ T-lymphocyte absolute count (CD4ac), CD4+ T-lymphocyte percentage (CD4%) and total lymphocyte count (Løac) were assessed in HIV-seropositive intravenous drug users (IVDU) with reference to their correlation with the clinical categories A, B, and C as stipulated by the Centre of Disease Control and Prevention, USA (CDC) and with each other. It was found that while the CD4ac and Løac correlated with the clinical categories, CD4% did not. This may suggest that in our local setting, the CD4% may not necessarily be a suitable alternative marker to CD4ac as proposed by CDC. Furthermore, the CD4% of the normal subjects in this study was found to be relatively lower than the reported Caucasian levels. This may indicate that the use of the cut-off level of less than 14% as an AIDS-defining criteria may not be applicable for our HIV-seropositive IVDU. In addition, unlike the CD4ac which correlated directly with CD4% and Løac, the CD4% did not correlate with Løac. Therefore, due to the observed disparity with clinical status of patients and its possibly lower levels in our normal population, CD4% as a marker for staging HIV disease should be used with caution in our setting. Such findings may also have an impact on the use of established markers for the monitoring and classification of HIV-infected individuals in this region.
    Matched MeSH terms: CD4-CD8 Ratio
  7. Orbital rhabdomyosarcoma in an HIV positive child
    Khairy-Shamel ST, Shatriah I, Adil H, Zunaina E, Bakiah S, Rohaizan Y, et al.
    Orbit, 2008;27(5):388-90.
    PMID: 18836940 DOI: 10.1080/01676830802336629
    We reported a case of orbital rhabdomyosarcoma with an intracranial extension in an HIV-infected child. It was an uncommon sarcoma in a retroviral-positive patient that resulted in a diagnostic and therapeutic dilemma. The child is currently asymptomatic following surgery, chemotherapy, and reinstitution of highly active retroviral therapy (HAART).
    Matched MeSH terms: CD4-CD8 Ratio
  8. Role of CD4 and CD8 T-cells in the induction of oral tolerance to Actinomyces viscosus in mice
    Sosroseno W, Bird PS, Gemmell E, Seymour GJ
    Oral Microbiol. Immunol., 2006 Jun;21(3):151-8.
    PMID: 16626371
    Mucosal presentation of Actinomyces viscosus results in the induction of antigen specific systemic suppressor cells in mice. The aim of the present study was to determine the phenotype of the suppressor cells responsible for the induction of oral tolerance to low doses of A. viscosus. When CD8 cell-depleted DBA/2 mice were intragastrically immunized and systemically immunized with A. viscosus, the delayed type hypersensitivity response was suppressed but not the levels of antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4(+) cells to CD4(+)-depleted mice resulted in suppression of delayed type hypersensitivity response but not of the levels of antigen specific serum antibodies. In contrast, adoptive transfer of orally immunized CD8(+) cells to CD8(+)-depleted mice resulted in partially suppressed delayed type hypersensitivity response but significantly inhibited the levels of antigen specific serum antibodies. When orally tolerized CD8(+) cells were cocultured with systemically immunized CD8(+) cell-depleted spleen cells, splenic specific antibodies were inhibited. However, no suppression of splenic specific antibodies could be observed in the cultures containing orally tolerized CD4(+) cells and systemically immunized CD4(+) cell-depleted spleen cells. The results of the present study suggest that oral tolerance of humoral and cellular immunity induced by low doses of A. viscosus may be mediated by CD8(+) and CD4(+) cells, respectively.
    Matched MeSH terms: CD4-CD8 Ratio
  9. Autoimmune thrombocytopenia and neutropenia after autologous peripheral blood stem cell transplantation
    Wahid FS, Cheong SK, Sivagengei K
    Acta Haematol., 2002;107(4):237-8.
    PMID: 12053154
    Matched MeSH terms: CD4-CD8 Ratio
  10. Phyllanthin from Phyllanthus amarus inhibits cellular and humoral immune responses in Balb/C mice
    Ilangkovan M, Jantan I, Bukhari SN
    Phytomedicine, 2016 Nov 15;23(12):1441-1450.
    PMID: 27765364 DOI: 10.1016/j.phymed.2016.08.002
    BACKGROUND: Phyllanthin found in many Phyllanthus species has various biochemical and pharmacological properties especially on its hepatoprotective effects. However, its effect on the immune system has not been well documented.

    PURPOSE: In the present study, phyllanthin isolated from Phyllanthus amarus was investigated for its immunosuppressive effects on various cellular and humoral immune responses in Balb/C mice.

    METHODS: Male mice were treated daily at 20, 40 and 100mg/kg of phyllanthin for 14 days by oral gavage. The effects of phyllanthin on cellular immune responses in treated /non treated mice were determined by measuring CD 11b/CD 18 integrin expression, phagocytosis, nitric oxide (NO) production, myeloperoxidase activity (MPO), T and B cells proliferation, lymphocyte phenotyping, serum cytokines production by activated T-cells and delayed type hypersensitivity (DTH). Its effects on humoral immune responses were evaluated by determining the serum levels of lysozyme and ceruloplasmin, and immunoglobulins (IgG and IgM).

    RESULTS: Phyllanthin dose-dependently inhibited CD11b/CD18 adhesion, the engulfment of E. coli by peritoneal macrophages molecules, NO and MPO release in treated mice. Phyllanthin caused significant and dose-dependent inhibition of T and B lymphocytes proliferation and down-regulation of the Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines. Phyllanthin at 100mg/kg caused a significant reduction in the percentage expression of CD4(+) and CD8(+) in splenocytes and the inhibition was comparable to that of cyclosporin A at 50mg/kg. At 100mg/kg, phyllanthin also dose-dependently exhibited strong inhibition on the sheep red blood cell (sRBC)-induced swelling rate of mice paw in DTH. Significant inhibition of serum levels of ceruloplasmin and lysozyme were observed in mice fed with higher doses (40 and 100mg/kg) of phyllanthin. Anti-sRBC immunoglobulins (IgM and IgG) antibody titer was down-regulated in immunized and phyllanthin-treated mice in a dose-dependent manner with maximum inhibition being observed at 100mg/kg.

    CONCLUSION: The strong inhibitory effects of phyllanthin on the cellular and humoral immune responses suggest that phyllanthin may be a good candidate for development into an effective immunosuppressive agent.

    Matched MeSH terms: CD4-CD8 Ratio
  11. Phenotyping of lymphocytes expressing regulatory and effector markers in infiltrating ductal carcinoma of the breast
    Leong PP, Mohammad R, Ibrahim N, Ithnin H, Abdullah M, Davis WC, et al.
    Immunol Lett, 2006 Feb 15;102(2):229-36.
    PMID: 16246429
    Dysfunction of the host immune system in cancer patients can be due to a number of reasons including suppression of tumour associated antigen reactive lymphocytes by regulatory T (Treg) cells. In this study, we used flow cytometry to determine the phenotype and relative abundance of the tumour infiltrating lymphocytes (TILs) from 47 enzymatically dissociated tumour specimens from patients with infiltrating ductal carcinoma (IDC) of the breast. The expression of both effector and regulatory markers on the TILs were determined by using a panel of monoclonal antibodies. Analysis revealed CD8(+) T cells (23.4+/-2.1%) were predominant in TILs, followed by CD4(+) T cells (12.6+/-1.7%) and CD56(+) natural killer cells (6.4+/-0.7%). The CD4(+)/CD8(+) ratio was 0.8+/-0.9%. Of the CD8(+) cells, there was a higher number (68.4+/-3.5%) that expressed the effector phenotype, namely, CD8(+)CD28(+) and about 46% of this subset expressed the activation marker, CD25. Thus, a lower number of infiltrating CD8(+) T cells (31.6+/-2.8%) expressed the marker for the suppressor phenotype, CD8(+)CD28(-). Of the CD4(+) T cells, 59.6+/-3.9% expressed the marker for the regulatory phenotype, CD4(+)CD25(+). About 43.6+/-3.8% CD4(+)CD25(+) subset co-expressed both the CD152 and FOXP3, the Treg-associated molecules. A positive correlation was found between the presence of CD4(+)CD25(+) subset and age (> or =50 years old) (r=0.51; p=0.045). However, no significant correlation between tumour stage and CD4(+)CD25(+) T cells was found. In addition, we also found that the CD4(+)CD25(-) subset correlated with the expression of the nuclear oestrogen receptor (ER)-alpha in the tumour cells (r=0.45; p=0.040). In conclusion, we detected the presence of cells expressing the markers for Tregs (CD4(+)CD25(+)) and suppressor (CD8(+)CD28(-)) in the tumour microenvironment. This is the first report of the relative abundance of Treg co-expressing CD152 and FOXP3 in breast carcinoma.
    Matched MeSH terms: CD4-CD8 Ratio
  12. Fulltext Perturbation of cellular immune functions in cigarette smokers and protection by palm oil vitamin E supplementation
    Jubri Z, Latif AA, Top AG, Ngah WZ
    Nutr J, 2013;12:2.
    PMID: 23286246 DOI: 10.1186/1475-2891-12-2
    BACKGROUND:
    Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee), is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers.

    METHODS:
    This study involved a group of smokers and nonsmokers who received 200 mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24 weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT) and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann-Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman.

    RESULTS:
    Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α1-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4+ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4+/CD8+ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4+ and B cells.

    CONCLUSIONS:
    Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3+, CD4+, CD8+, NK cells and B cells except B cells percentage in nonsmokers.
    Matched MeSH terms: CD4-CD8 Ratio
  13. Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8(+) T cells in HIV/TB co-infection
    Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
    Matched MeSH terms: CD4-CD8 Ratio
  14. Fulltext Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma
    Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA
    BMC Immunol, 2008;9:73.
    PMID: 19087256 DOI: 10.1186/1471-2172-9-73
    BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.
    RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found.
    CONCLUSION: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.
    Matched MeSH terms: CD4-CD8 Ratio
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