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1.
Br J Dermatol ; 186(1): 50-58, 2022 01.
Article in English | MEDLINE | ID: mdl-33511639

ABSTRACT

BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.


Subject(s)
Dermatitis, Atopic , Eczema , Cohort Studies , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/epidemiology , Eczema/diagnosis , Eczema/epidemiology , Humans , Incidence , Infant , Pruritus
2.
Br J Dermatol ; 186(3): 544-552, 2022 03.
Article in English | MEDLINE | ID: mdl-34698386

ABSTRACT

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.


Subject(s)
Dermatitis, Atopic , Eczema , Filaggrin Proteins/genetics , Dermatitis, Atopic/genetics , Eczema/genetics , Genotype , Humans , Infant , Intermediate Filament Proteins/genetics , Intermediate Filament Proteins/metabolism , Mutation/genetics , Skin/metabolism
4.
Clin Exp Immunol ; 167(3): 492-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22288592

ABSTRACT

Based on the ability to recruit lymphocytes and dendritic cells to lymphoid tissue and to promote inflammation, we hypothesized a role for dysregulated CCL19 and CCL21 levels in human immunodeficiency virus (HIV)-infected patients with advanced immunodeficiency, and in particular in those with accompanying Mycobacterium avium complex (MAC) infection. The hypothesis was explored by studies in HIV-infected patients with and without MAC infection, as well as in vitro, examining the ability of proteins from MAC to promote CCL19 and CCL21 responses in peripheral blood mononuclear cells (PBMC) during highly active anti-retroviral therapy (HAART). Our main findings were: (i) raised serum levels of CCL19 in HIV-infected patients with CD4(+) T cell count <50 cells/µl compared with HIV-infected patients with CD4(+) T cell count >500 cells/µl and healthy controls, with particularly high levels in those with MAC infection; (ii) elevated plasma levels of CCL19 predicted a higher mortality in acquired immune deficiency syndrome (AIDS)-patients, independent of ongoing MAC infection; and (iii) marked production of CCL19 in MAC-stimulated peripheral blood mononuclear cells (PBMC) and pronounced disturbances in MAC-induced CCL19 production in PBMC from HIV patients that was partly reversed during HAART. Our findings suggest the involvement of CCL19 in AIDS patients with advanced immunodeficiency, potentially mediating both adaptive and maladaptive responses.


Subject(s)
Acquired Immunodeficiency Syndrome/immunology , Chemokine CCL19/blood , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/immunology , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Antiretroviral Therapy, Highly Active , Bacterial Proteins/immunology , Biomarkers/blood , Case-Control Studies , Chemokine CCL21/blood , Female , Humans , In Vitro Techniques , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Male , Middle Aged , Mycobacterium avium Complex/immunology , Mycobacterium avium-intracellulare Infection/blood , Mycobacterium avium-intracellulare Infection/immunology , Prognosis
6.
Clin Exp Immunol ; 157(3): 400-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19664149

ABSTRACT

CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P < 0.01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin-stimulated CCL19 release in both PBMC (P < 0.01) and BMMC (P < 0.05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8(+)CCR7(-)CD45RA(-) T cells in peripheral blood [P < 0.01 and P < 0.05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV-tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV-infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.


Subject(s)
Chemokine CCL19/immunology , Chemokine CCL21/immunology , HIV Infections/immunology , T-Lymphocytes/immunology , Adult , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Bone Marrow Cells/chemistry , Case-Control Studies , Chemokine CCL19/analysis , Chemokine CCL21/analysis , Cross-Sectional Studies , Female , HIV Infections/drug therapy , Homeostasis , Humans , Immunologic Memory , Leukocytes, Mononuclear/chemistry , Male , Receptors, CCR7/analysis , Statistics, Nonparametric , Treatment Failure , Viral Load , Virus Replication , Young Adult
7.
Eur J Clin Invest ; 39(11): 1017-24, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19674076

ABSTRACT

BACKGROUND: While some chemokines are thought to be protective in HIV-infected individuals by their ability to block HIV entry into T cells and macrophages, chemokines could also have harmful effects in HIV infection through their ability to promote inflammation. Here, we examined the regulation and the effects of CXCL16, a newly discovered chemokine of the CXC family, in HIV-infected patients. MATERIALS AND METHODS: We examined serum levels of CXCL16 in clinically well-defined subgroups of HIV-infected individuals both before (n = 62) and during HAART (n = 40) as well as in age- and sex-matched healthy controls (n = 30). We also examined the effects of CXCL16 on inflammatory and anti-inflammatory cytokines and HIV replication in peripheral blood mononuclear cells (PBMC). RESULTS: Our main and novel findings were: (i) HIV-infected patients had significant raised CXCL16 levels according to disease severity and progression. (ii) During HAART, the immunological improvement was accompanied by a modest increase in CXCL16 level. (iii) While soluble CXCL16 promoted an anti-inflammatory response in PBMC from those on successful HAART, it induced an inflammatory response and enhanced HIV replication in PBMC from those with high viral load irrespectively of ongoing HAART. (iv) Recombinant HIV-tat protein significantly increased CXCL16 release in THP-1 macrophages. CONCLUSIONS: Our findings suggest a complex interaction between CXCL16 and HIV, promoting both inflammatory and anti-inflammatory effects as well as HIV replication, partly dependent on accompanying HIV replication.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Chemokines, CXC/immunology , HIV Infections/immunology , HIV-1/immunology , Receptors, Scavenger/immunology , Virus Replication/immunology , Adult , Antiretroviral Therapy, Highly Active , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Cells, Cultured , Chemokine CXCL16 , Cross-Sectional Studies , Female , HIV Infections/drug therapy , Humans , Male , RNA, Viral/immunology , Viral Load , Virus Replication/drug effects
8.
Clin Exp Immunol ; 152(1): 57-63, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18241231

ABSTRACT

Although neutrophil gelatinase-associated lipocalin (NGAL) may play a pivotal role in the innate immune response, there are currently no data on NGAL levels in human immunodeficiency virus (HIV)-infected patients. In this study we aimed to examine the regulation of NGAL in HIV infection. The regulation of NGAL in HIV infection was examined by different experimental approaches, including studies in peripheral blood and mononuclear cells (MNC) from bone marrow aspirates before and during highly active anti-retroviral therapy (HAART). We found that: before initiating HAART, HIV-infected patients (n = 37) had significantly decreased serum NGAL levels compared with healthy controls (n = 26); (ii) during HAART, there was a gradual and significant increase in NGAL concentrations reaching levels comparable to those in healthy controls after 12 months; (iii) this increase was seen primarily in virological responders to HAART (HIV RNA level <200 copies/ml after 24 months); (iv) phytohaemagglutinin-stimulated NGAL release in MNC cells from bone marrow aspirates was decreased in untreated HIV-infected patients compared with healthy controls, but increased after 26 weeks on HAART; and (v) there was a significant positive correlation between neutrophil counts and NGAL levels at all time-points during HAART. We have shown decreased NGAL levels in HIV-infected patients, potentially reflecting decreased number and function of neutrophils as well as impaired bone marrow myelopoiesis. These abnormalities were reversed by successful HAART. Our findings underscore further the involvement of neutrophils and innate immunity in HIV-related immunodeficiency.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/blood , HIV-1/isolation & purification , Lipocalins/blood , Proto-Oncogene Proteins/blood , Acute-Phase Proteins , Adult , Antiretroviral Therapy, Highly Active , Bone Marrow Cells/metabolism , CD4 Lymphocyte Count , Cells, Cultured , Female , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Lipocalin-2 , Male , Middle Aged , Neutrophils/metabolism , RNA, Viral/blood , Viral Load
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