Lymphocyte subsets in alcoholic liver disease

Matos, Luís Costa; Batista, Paulo; Monteiro, Nuno P.; Ribeiro, João; Cipriano, Maria Augusta; Henriques, Pedro; Girão, Fernando; Carvalho, Armando

doi:10.4254/wjh.v5.i2.46

Cited by 35 publications

(39 citation statements)

References 50 publications

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“…This is consistent with previous studies of healthy donors, in which ratios of 2.0 and 2.3 were observed. 25,26 In the nickel-allergic cohort, a significant decrease in the CD4 + /CD8 hi ratio was shown in strongly allergic individuals (++; P < 0.05), whereas, in the PPD-allergic donors, there was a marked decrease in the CD4 + /CD8 hi ratio in the weakly, strongly and extremely allergic cohorts (combined population as compared with buffy coat samples; P < 0.001). To complement the previous studies of T cell dynamics in allergy to MI, the ratio of CD4 + to CD8 hi cells was measured for an additional cohort of 27 MI-allergic individuals (+, 14; ++, 7; +++, 6).…”

Section: Characterization Of T Lymphocyte Naïve and Memory Populatimentioning

confidence: 95%

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

et al. 2019

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Background: There is considerable interest in understanding the immunological variables that have the greatest influence on the effectiveness of sensitization by contact allergens, particularly in the context of developing new paradigms for risk assessment of novel compounds.Objectives: To examine the relationship between patch test score for three different contact allergens and the characteristics of T cell responses.Methods: A total of 192 patients with confirmed nickel, p-phenylenediamine (PPD) or methylisothiazolinone (MI) allergy were recruited from the Contact Dermatitis Investigation Unit at Salford Royal Hospital. Severity of allergy was scored by the use of patch testing, peripheral blood lymphocytes were characterized for T cell phenotype by flow cytometry, and proliferative activity was characterized by radiolabelled thymidine incorporation. Comparisons were drawn with buffy coat samples from healthy volunteers.Results: Patch test positivity for nickel, PPD and MI was associated with changes in the phenotype of peripheral blood T cells: increases in naïve cells, decreases in regulatory T cell frequency and the CD4 + /CD8 hi ratio, and increased expression of the skin-homing marker cutaneous lymphocyte antigen (CLA), particularly for those patients with a +++ patch test score.Conclusions: This increased understanding of the characteristics of the T cell responses to contact allergens may provide parameters with which to better measure health risks associated with skin sensitization. K E Y W O R D SCD4, CD8, inverted CD4/CD8, skin-homing CLA, lymphocyte transformation test, T cell phenotype, RRID:SCR_001905

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Section: Characterization Of T Lymphocyte Naïve and Memory Populatimentioning

confidence: 95%

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

et al. 2019

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“…Relative lymphopenia plays an important role as well as an inflammatory neutrophilia; lymphopenia along with an increased CD4+/CD8 + ratio has been noted in alcohol-related liver disease previously. 11 The aim of this study was to assess whether baseline NLR might be used to identify steroid responders among a cohort of patients with severe alcoholic hepatitis.…”

Section: Introductionmentioning

confidence: 99%

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Forrest

Storey

Sinha³

et al. 2019

Aliment Pharmacol Ther

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Summary Background Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess “response”. Aim To assess the prognostic and therapeutic implications of baseline neutrophil‐to‐lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. Methods Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan‐Meier analysis was used to assess survival. Log‐rank test and odds ratio (OR) were used for comparative analysis. Results Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90‐day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety‐day survival was not affected by prednisolone treatment if NLR < 5 or > 8 but mortality was reduced with prednisolone treatment when the NLR was 5‐8 (21.0% cf. 34.5%; P = 0.012). Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow alcoholic hepatitis score (mGAHS) improved the AUC to 0.783 and 0.739 for 28‐day and 90‐day outcome, respectively. Conclusion The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5‐8). The mGAHS has a good predictive value for 28‐ and 90‐day outcomes.

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“…(6,20) Alcohol abuse also affects multiple aspects of B cellmediated immunity, (6,21,22) leading to reduced numbers and function of B cells while simultaneously increasing production of immunoglobulins. (6,21,22) Particularly, levels of autoantibodies against liverspecific antigens are increased in AH patients and may promote alcohol-related liver damage. (6) Due to alcohol-induced impairment of both innate and adaptive immunity, chronic alcohol drinkers are more susceptible to many infectious pathogens with delayed infection recovery, thus extending hospital stays and increasing morbidity and mortality.…”

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confidence: 99%

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study

Amet

Xing

et al. 2017

Hepatology

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Alcoholic hepatitis (AH) develops only in small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls (HC) were enrolled and followed up to 12 months. At the baseline, HDC and HC had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays. However, compared to HDC, AH patients had higher baseline levels of 11 cytokines/chemokines (TNF-α, IL-6, IL-8, IP10, IL-4, IL-9, IL-10, FGF-2, IL-7, IL-15, and TGF-α), but lower levels of the anti-inflammatory macrophage-derived chemokine (MDC). AH patients also had more activated, yet dysfunctional immune cells as monocytes, T cells, and B cells expressed higher levels of CD38 and CD69, but low levels of HLA-DR, CD80, and CD86 at baseline. In addition, CD4 T cells produced less IFN-γ in response to T cell stimulation. Upregulated IL-6, IL-8, CD38, and CD69 and downregulated MDC, HLA-DR, CD86, and CD80 correlated positively and negatively, respectively, with disease severity. Longitudinal analysis indicated that levels of IL-6, IL-8, CD38, and CD69 were reduced, whereas levels of MDC, HLA-DR, CD80, and CD86 were increased in abstinent AH patients. All of the cellular immune abnormalities were reversed by day 360 in abstinent AH patients; however, plasma levels of TNF-α, IL-8, IL-10, FGF-2, and IL-7 remained higher. Conclusion: AH patients were in a highly immune-dysregulated state, whereas HDC showed little evidence of immune activation. Alcohol abstinence reversed most, but not all, of the immunological abnormalities.

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Lymphocyte subsets in alcoholic liver disease

Abstract: All patient subsets presented with decreased lymphocyte counts, but only patients with advanced fibrosis presented with a significant increase in the CD4(+)/CD8(+) ratio.

Cited by 35 publications

References 50 publications

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Alcohol abstinence ameliorates the dysregulated immune profiles in patients with alcoholic hepatitis: A prospective observational study

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