Decreased Enteric Bacterial Composition and Diversity in South American Crohn's Disease Vary With the Choice of Treatment Strategy and Time Since Diagnosis.

BACKGROUND AND AIMS: The symptomology of Crohn's disease [CD], a chronic inflammatory disease of the digestive tract, correlates poorly with clinical, endoscopic or immunological assessments of disease severity. The prevalence of CD in South America is rising, reflecting changes in socio-economic stability. Many treatment options are available to CD patients, including biological agents and corticosteroids, each of which offers variable efficacy attributed to host genetics and environmental factors associated with alterations in the gut microbiota. METHODS: Based on 16S rRNA gene sequencing and taxonomic differences, we compared the faecal microbial population of Brazilian patients with CD treated with corticosteroid or anti-tumour necrosis factor [anti-TNF] immunotherapy. Faecal calprotectin and plasma sCD14 levels were quantified as markers for local and systemic inflammation, respectively. RESULTS: Anti-TNF treatment led to an increased relative abundance of Proteobacteria and a decreased level of Bacteroidetes. In contrast, corticoid treatment was associated with an increase in the relative abundance of Actinobacteria, which has been linked to inflammation in CD. Disruption of the faecal microbiota was related to decreased bacterial diversity and composition. Moreover, the choice of clinical regimen and time since diagnosis modulate the character of the resulting dysbiosis. CONCLUSIONS: Enteric microbial populations in CD patients who have been treated are modulated by disease pathogenesis, local inflammatory microenvironment and treatment strategy. The dysbiosis that remains after anti-TNF treatment due to decreased bacterial diversity and composition abates restoration of the microbiota to a healthy state, suggesting that the identification and development of new clinical treatments for CD must include their capacity to normalize the gut microbiota.

Higher soluble CD14 levels are associated with lower visuospatial memory performance in youth with HIV.

OBJECTIVE: HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). DESIGN: Observational cross-sectional study. METHODS: YWH, ages 20-28 years, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation, and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically adjusted z-scores were combined to form indices of attention, motor, executive function, verbal, and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T-cell count, HIV viral load, and ART status. RESULTS: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z = -1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, whereas sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. CONCLUSION: Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14.

Campylobacter jejuni virulence genes and immune-inflammatory biomarkers association with growth impairment in children from Northeastern Brazil.

Campylobacter spp. have been associated with anthropometric Z-score decrements, but the role of specific virulence genes associated with these outcomes has not been explored. This study aimed to investigate whether specific Campylobacter jejuni virulence-related gene and immune-inflammatory biomarkers are associated with malnutrition in children from Northeastern Brazil. A case-control study was performed in Fortaleza, Brazil. Children aging 6-24 months were characterized as malnourished (cases) if weight-for-age Z-score (WAZ) = 2 and as nourished (controls) if WAZ ≥ 1. DNA samples were extracted from stools and screened for C. jejuni/coli by real-time PCR. A subsequent C. jejuni-specific PCR was employed and positive samples were evaluated for 18 C. jejuni virulence genes by using four multiplex PCRs. C. jejuni was detected in 9.71% (33/340) of the children's samples, being 63.63% (21/33) from nourished and 37.37% (12/33) from malnourished children. The cadF, iamA, cheW, and sodB genes were the most frequent genes (100%, 90.9%, 87.9%, and 75.8%, respectively), while some others (ceuE, jlpA, pldA, and pVir) showed low rates (all below 6%). Malnourished children were significantly associated with infection with C. jejuni strains lacking cdtB gene (active subunit of cytolethal distending toxin) and harboring flgE gene (flagellar hook protein). These strains were also associated with children presenting increased serum SAA and sCD-14, but decreased IgG anti-LPS. These data reinforce the impact of Campylobacter jejuni infection on children without diarrhea and highlight the contribution of a specific virulence gene profile, cdtB(-)flgE(+) and increased systemic response in malnutrition children.

Asymptomatic HIV People Present Different Profiles of sCD14, sRAGE, DNA Damage, and Vitamins, according to the Use of cART and CD4+ T Cell Restoration.

We aimed to analyze markers of immune activation, inflammation, and oxidative stress in 92 asymptomatic HIV-infected patients according to the adequate (AR, >500 cells/mm3) or inadequate (IR, <500 cells/mm3) CD4+ T recovery and the presence or absence of antiretroviral treatment (cART). In relation to those newly diagnosed, they were divided into two groups, cART-naïve IR (nIR) and cART-naïve AR (nAR). Among those diagnosed more than five years ago, the following division was made: the cART-naïve long-term nonprogressors (LTNP); patient under cART and AR (tAR); and patients under cART and IR (tIR). We investigated the expression of soluble receptor for advanced glycation end products (sRAGE), high-mobility group-box protein -1 (HMGB1), soluble CD14 (sCD14), IL-8, IL-10, 8-isoprostane, vitamins, and DNA damage. We observed higher levels of sRAGE in tAR as compared to nIR, nAR, LTNP, and more sCD14 than in nIR and nAR. As for IL-10 levels, we found nIR > nAR > LTNP > tAR > tIR. Higher levels of 8-isoprostane were observed in nIR. LTNP presented a higher retinol dosage than tAR and less genotoxic damage induced by oxidative stress than the other groups. We suggest that the therapy, despite being related to lesser immune activation and inflammation, alters the vitamin profile and consequently increases the oxidative stress of patients. In addition, the lowest genotoxic index for LTNP indicates that both VL and cART could be responsible for the increased DNA damage. More studies are needed to understand the influence of cART on persistent immune activation and inflammation.

Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS.

Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF ( p = 0.041) and enzyme-linked immunosorbent assay ( p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin ( p = 0.047), neutrophil CD64 expression by flow cytometry ( p = 0.037) and presepsin ( p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.

Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation in Treatment-Naive Ugandans Who Achieve Virologic Suppression.

BACKGROUND: Residual systemic inflammation persists despite suppressive antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes. We aimed to evaluate the association between ART adherence and inflammation in Ugandans living with HIV who were predominantly receiving nevirapine-based ART with a thymidine analog backbone and were virologically suppressed by conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition to CD8 T-cell activation, were measured at baseline and 6 months after ART initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA (<400 copies/mL) at their 6-month visit. Adherence was measured through medication event monitoring system and calculated as the ratio of observed/prescribed device openings per participant. We fit adjusted linear regression models to estimate the association between ART adherence and the log-transformed plasma concentrations of inflammatory biomarkers. RESULTS: We evaluated 282 participants (median age, 35 years; 70% women). The median (interquartile range) adherence was 93% (84-98). In the adjusted analyses, for every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95% confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0), and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14, respectively. CONCLUSIONS: Higher ART adherence was associated with lower levels of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans living with HIV who achieved viral suppression shortly after ART initiation. This suggests that ART adherence could have biological consequences beyond viral suppression. Whether ART adherence optimization in virologically suppressed individuals could reduce residual inflammation remains unknown.

Immune development in HIV-exposed uninfected children born to HIV-infected women.

Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1ß levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

BACKGROUND: We evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection. METHODS: Cryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured in plasma, whereas T-cell activation levels, defined as the frequencies of CD4 and CD8 T cells coexpressing HLA-DR and CD38, were measured in peripheral blood mononuclear cells. RESULTS: D-dimer levels were significantly lower at viral suppression (P = 0.031), whereas CRP and sCD14 levels remained similar to pre-ART levels. At viral suppression, levels of the soluble markers did not correlate with each other. CD4 T-cell counts pre-ART tended to modestly correlate with levels of D-dimer (r = 0.35; P = 0.058) and CRP (r = 0.33; P = 0.078). At 36 weeks after treatment interruption (week 72), D-dimer levels returned back to pre-ART levels. However, CD8 T-cell activation was significantly lower than pre-ART levels (35.8% at week 0 vs 28.9% at week 72; P = 0.004). CONCLUSIONS: Among the A5217 participants who started ART within the first 6 months of HIV infection, high levels of sCD14 and CRP remain similar to pre-ART levels, suggesting that immune damage occurring in the initial stages of infection persists despite short-term virologic suppression.

Immune development in HIV-exposed uninfected children born to HIV-infected women

ABSTRACT Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

The Severity of Visceral Leishmaniasis Correlates with Elevated Levels of Serum IL-6, IL-27 and sCD14.

BACKGROUND: Visceral leishmaniasis (VL) is a severe disease caused by infection with protozoa of the genus Leishmania. Classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of the inflammatory response. It is unclear why 90% of infected individuals do not develop the disease while a minority develop the classical form. Furthermore, among those that develop disease, a small group progresses to more severe form that is unresponsive to treatment. The presence of inflammatory mediators in serum could theoretically help to control the infection. However, there is also a release of anti-inflammatory mediators that could interfere with the control of parasite multiplication. In this study, we took advantage of the spectrum of outcomes to test the hypothesis that the immune profile of individuals infected with Leishmania (L.) infantum is associated with the development and severity of disease. METHODOLOGY/PRINCIPAL FINDINGS: Sera from patients with confirmed diagnosis of VL were evaluated for the presence of numerous molecules, and levels compared with healthy control and asymptomatic infected individuals. CONCLUSIONS/PRINCIPAL FINDINGS: Although differences were not observed in LPS levels, higher levels of sCD14 were detected in VL patients. Our data suggest that L. infantum may activate the inflammatory response via CD14, stimulating a generalized inflammatory response with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL-10, IL-6 and sCD14. These molecules were strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml were strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in the immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum.

Protective Profile Involving CD23/IgE-mediated NO Release is a Hallmark of Cutaneous Leishmaniasis Patients from the Xakriabá Indigenous Community in Minas Gerais, Brazil.

In this study, we described, for the first time, specific aspects of an anti-Leishmania immune response in a Brazilian Xakriabá indigenous community. Induction of an intracellular NO pathway, triggered by the binding of IgE to CD23 receptor in IFN-γ/IL-4 cytokines environment, was evaluated in localized cutaneous leishmaniasis (LCL) carriers and positive Montenegro skin test (MST) individuals without skin lesion (MT(+) SL(-)). Our data demonstrated that the higher frequency of CD23(+) CD14(+) monocytes and the increased serum levels of IgE observed in the LCL group were even higher in LCL carriers with late lesions (LCL≥60). Furthermore, patients with LCL presented increased NO production after Leishmania (Viannia) braziliensis stimulation and this NO profile was independent of the time of the lesion (recent LCL<60 or late LCL≥60). We also showed that the increased frequency of IFN-γ(+) and IL-4(+) CD4(+) T cells is related to the MT(+) SL(-) group. The results of biomarker signature curves demonstrated that in the MT(+) SL(-) group, the index signature was characterized by DAF-2T(+) CD14(+)/IL-4(+) CD8(+)/IFN-γ(+) CD4(+)/IL-4(+) CD4(+). On the other hand, the LCL group presented a higher index of DAF-2T(+) CD14(+)/CD23(+) CD14(+)/IL-4(+) CD8(+), associated with a lower index of IFN-γ(+) CD8(+). Considering the time of lesion, data analysis demonstrated that the main differences observed were highlighted in LCL<60 patients, with a higher index of CD23(+) CD14(+), which was also present in LCL≥60 patients. In conclusion, our data suggest that the protective immune response involving CD23-IgE-mediated NO release is a hallmark of patients with LCL. However, in MT(+) SL(-) individuals, another different leishmanicidal mechanism seems to be involved.

Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes.

Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.

Reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes and normal CD14 soluble levels in juvenile systemic lupus erythematosus.

In order to evaluate Fas and Bcl-2 expressions in CD14+ monocytes, to measure soluble CD14 serum levels and to analyze the relationships with lupus nephritis and disease activity, we enrolled 41 patients with juvenile systemic lupus erythematosus (JSLE) and 27 healthy volunteers. Disease activity was determined by SLEDAI score. Peripheral monocytes were stained for CD14, Fas and Bcl-2 molecules, and cellular expressions were determined by flow cytometry. Soluble CD14 levels were measured by a quantitative ELISA kit. JSLE patients, those with active disease and those with nephritis, presented significantly reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes compared with healthy controls. Significant inverse correlations between percentages of CD14+Fas+ cells, SLEDAI score and anti-dsDNA antibodies were observed. JSLE patients had soluble CD14 levels similar to controls, although sCD14 levels positively correlated with ESR, but not with SLEDAI score. JSLE patients with nephritis also presented sCD14 levels similar to controls. In conclusion, the reduced expressions of Fas and Bcl-2 proteins in CD14+ monocytes from JSLE patients depict that monocyte apoptotic mechanisms may be important in lupus pathogenesis.

Expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on osteoclasts and its potential role in rheumatoid arthritis.

OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis.

Microbial translocation induces an intense proinflammatory response in patients with visceral leishmaniasis and HIV type 1 coinfection.

BACKGROUND: Leishmania infection is a cofactor in the heightened cellular activation observed in patients with American visceral leishmaniasis and human immunodeficiency virus type 1 (HIV) infection, with or without progression to AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite antileishmanial therapy could be responsible for the continued immune stimulation. METHODS: CD8(+) T cells expressing CD38, parasite load, lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory cytokines (interleukin 1ß, interleukin 6, interleukin 8, interleukin 17, interferon γ, and tumor necrosis factor) were measured in 17 patients with AVL/HIV, 16 with HIV, and 14 healthy subjects (HS). RESULTS: Lower Leishmania parasitemia was observed after antileishmanial and antiretroviral therapies. However, higher levels of CD38(+) on CD8(+) T cells were observed in both clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine levels were significantly augmented in patients with active coinfection, as well as those with remission of Leishmania infection. LPS levels and Leishmania infection were positively correlated with CD38 expression on CD8(+) T cells and with IL-6 and IL-8 levels. CONCLUSIONS: LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.

Assessment of nutritional status: vitamin A and zinc in patients with common variable immunodeficiency.

BACKGROUND: Patients with common variable immunodeficiency (CVID) present with low antibody levels, impaired lymphocyte function, and chronic inflammation. Vitamin A and zinc are essential components of the immune system and can be redistributed in the body as a result of inflammation. OBJECTIVE: To compare levels of retinol, beta-carotene, and zinc in patients with CVID and healthy controls after evaluating a series of parameters for each participant. PATIENTS AND METHODS: We performed a cross-sectional study of CVID patients and healthy controls matched for age and gender. All participants underwent a nutritional and laboratory evaluation comprising a complete blood count and determination of levels of C-reactive protein (CRP), lipopolysaccharide (LPS), soluble CD14 (sCD14), retinol, beta-carotene, and serum and erythrocyte zinc. RESULTS: We included 17 patients (mean age, 28.54 years) and 17 controls. Mean (SD) retinol levels were lower in patients: 1.99 (0.67) micromol/L vs 2.72 (0.96) micromol/L. Median beta-carotene levels were similar in both groups (0.30 micromol/L). Median serum zinc levels were 50.0 microg/dL (50-100 microg/dL) in the patients and 100.0 microg/dL (50-150 microg/dL) in the controls. Mean levels of erythrocyte zinc were lower among patients: 37.32 (10.51) microgZn/gHb vs 44.91 (7.67) microgZn/gHb in the controls. Median CRP levels were significantly higher among patients: 4.99 (0.15-34.51) mg/L vs 0.55 (0.17-6.06) mg/L. No differences in translocation marker levels were observed between the groups. CONCLUSIONS: CVID patients had lower levels of retinol and zinc than controls. Since micronutrient deficiency could aggravate their disease and contribute to chronic inflammation, micronutrient status should always be assessed in patients with primary immunodeficiency.

Aggressive and chronic periodontitis correlate with distinct cellular sources of key immunoregulatory cytokines.

BACKGROUND: Chronic periodontitis (CP) and aggressive periodontitis (AP) are inflammatory diseases and the main cause of dental loss in adults. We aimed to investigate the expression of adhesion molecules and the source of proinflammatory and anti-inflammatory cytokines in circulating mononuclear cells from patients with CP and AP. METHODS: Peripheral blood mononuclear cells from healthy controls and CP or AP patients were collected. The expression of the cell adhesion molecules CD11a and CD11b, and the cellular sources of interleukin (IL)-4, IL-10, IL-12, interferon-γ, and tumor necrosis factor-α by distinct subpopulations of circulating leukocytes were determined using flow cytometry. RESULTS: The expression of CD11a, but not CD11b, was significantly higher within the CD4(+) and CD8(+) T cells in CP and AP than in healthy controls. The frequencies of tumor necrosis factor-α-expressing CD4(+) T cells and CD14(+) cells were higher in AP and CP, compared to healthy controls, respectively. Moreover, the frequency of IL-10 expressing CD14(+) cells was higher in CP, but not AP, compared to healthy controls CD4(+) T cells committed to IL-4 production was higher in CP than in healthy controls. CONCLUSION: These results suggest the participation of CD11a in the pathogenesis of periodontal lesions and show distinct cellular sources of immunoregulatory cytokines in AP versus CP.