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Harri Alenius

Bio: Harri Alenius is an academic researcher from Karolinska Institutet. The author has contributed to research in topics: Immunoglobulin E & Allergy. The author has an hindex of 63, co-authored 264 publications receiving 15819 citations. Previous affiliations of Harri Alenius include National Institute of Occupational Health & Finnish Institute of Occupational Health.


Papers
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Journal ArticleDOI
TL;DR: The findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis, and show that IL-31 may represent a novel target for antipruritic drug development.
Abstract: Background IL-31 is a novel T-cell–derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. Objective To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. Methods The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. Results IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo , staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro , staphylococcal enterotoxin B but not viruses or T H 1 and T H 2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Conclusion Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.

867 citations

Journal ArticleDOI
TL;DR: Analyzing atopic sensitization in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, it is shown that environmental biodiversity in the surroundings of the study subjects’ homes influenced the composition of the bacterial classes on their skin.
Abstract: Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the “biodiversity hypothesis,” reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects’ homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.

812 citations

Journal ArticleDOI
TL;DR: This meta-analysis confirms a robust link between IL-6, CRP and major depression and the role of TNF-α and IL-1β in major depression remains uncertain.
Abstract: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d = 0.54, p < 0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d = 0.47, p < 0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d = 0.40, p = 0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d = −0.05, p = 0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression.

757 citations

Journal ArticleDOI
TL;DR: It is reported that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10, indicating that CCL27–CCR10 interactions have a pivotal role in T cell–mediated skin inflammation.
Abstract: The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-α and interleukin-1β induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27–CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27–CCR10 interactions have a pivotal role in T cell–mediated skin inflammation.

738 citations

Journal ArticleDOI
11 Jul 2007-PLOS ONE
TL;DR: It is shown for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema.
Abstract: MicroRNAs are a recently discovered class of posttranscriptional regulators of gene expression with critical functions in health and disease. Psoriasis is the most prevalent chronic inflammatory skin disease in adults, with a substantial negative impact on the patients' quality of life. Here we show for the first time that psoriasis-affected skin has a specific microRNA expression profile when compared with healthy human skin or with another chronic inflammatory skin disease, atopic eczema. Among the psoriasis-specific microRNAs, we identified leukocyte-derived microRNAs and one keratinocyte-derived microRNA, miR-203. In a panel of 21 different human organs and tissues, miR-203 showed a highly skin-specific expression profile. Among the cellular constituents of the skin, it was exclusively expressed by keratinocytes. The up-regulation of miR-203 in psoriatic plaques was concurrent with the down-regulation of an evolutionary conserved target of miR-203, suppressor of cytokine signaling 3 (SOCS-3), which is involved in inflammatory responses and keratinocyte functions. Our results suggest that microRNA deregulation is involved in the pathogenesis of psoriasis and contributes to the dysfunction of the cross talk between resident and infiltrating cells. Taken together, a new layer of regulatory mechanisms is involved in the pathogenesis of chronic inflammatory skin diseases.

731 citations


Cited by
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Journal ArticleDOI
TL;DR: This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists, and it is concluded that hepatitis D virus cannot be classified as a human carcinogen.
Abstract: Viral hepatitis in all its forms is a major public health problem throughout the world, affecting several hundreds of millions of people. Viral hepatitis is a cause of considerable morbidity and mortality both from acute infection and chronic sequelae which include, in the case of hepatitis B, C and D, chronic active hepatitis and cirrhosis. Hepatocellular carcinoma, which is one of the 10 commonest cancers worldwide, is closely associated with hepatitis B and, at least in some regions of the world, with hepatitis C virus. This timely monograph is a distillation of knowledge of hepatitis B, C and D, based on a review of 1000 studies by a small group of scientists. (It is interesting to note in passing that some 5000 papers on viral hepatitis are published annually in the world literature.) The epidemiological, clinical and experimental data on the association between infection with hepatitis B virus and primary liver cancer in humans are reviewed in a readable and succinct format. The available information on hepatitis C and progression to chronic infection is also evaluated and it is concluded (perhaps a little prematurely) that hepatitis C virus is carcinogenic. However, it is concluded that hepatitis D virus, an unusual virus with a number of similarities to certain plant viral satellites and viroids, cannot be classified as a human carcinogen. There are some minor criticisms: there are few illustrations and some complex tabulations (for example, Table 6) and no subject index. A cumulative cross index to IARC Monographs is of little value and occupies nearly 30 pages. This small volume is a useful addition to the overwhelming literature on viral hepatitis, and the presentation is similar to the excellent World Health Organisation Technical Reports series on the subject published in the past. It is strongly recommended as a readable up-to-date summary of a complex subject; and at a cost of 65 Sw.fr (approximately £34) is excellent value. A J ZUCKERMAN

11,533 citations

Journal ArticleDOI
21 Jul 1979-BMJ
TL;DR: It is suggested that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units, outpatients, and referrals to social services, but for house doctors to assess overdoses would provide no economy for the psychiatric or social services.
Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

4,497 citations

01 Feb 2015
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Abstract: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

4,409 citations

Journal ArticleDOI
Jean Bousquet, N. Khaltaev, Alvaro A. Cruz1, Judah A. Denburg2, W. J. Fokkens3, Alkis Togias4, T. Zuberbier5, Carlos E. Baena-Cagnani6, Giorgio Walter Canonica7, C. van Weel8, Ioana Agache9, Nadia Aït-Khaled, Claus Bachert10, Michael S. Blaiss11, Sergio Bonini12, L.-P. Boulet13, Philippe-Jean Bousquet, Paulo Augusto Moreira Camargos14, K-H. Carlsen15, Y. Z. Chen, Adnan Custovic16, Ronald Dahl17, Pascal Demoly, H. Douagui, Stephen R. Durham18, R. Gerth van Wijk19, O. Kalayci19, Michael A. Kaliner20, You Young Kim21, Marek L. Kowalski, Piotr Kuna22, L. T. T. Le23, Catherine Lemière24, Jing Li25, Richard F. Lockey26, S. Mavale-Manuel26, Eli O. Meltzer27, Y. Mohammad28, J Mullol, Robert M. Naclerio29, Robyn E O'Hehir30, K. Ohta31, S. Ouedraogo31, S. Palkonen, Nikolaos G. Papadopoulos32, Gianni Passalacqua7, Ruby Pawankar33, Todor A. Popov34, Klaus F. Rabe35, J Rosado-Pinto36, G. K. Scadding37, F. E. R. Simons38, Elina Toskala39, E. Valovirta40, P. Van Cauwenberge10, De Yun Wang41, Magnus Wickman42, Barbara P. Yawn43, Arzu Yorgancioglu44, Osman M. Yusuf, H. J. Zar45, Isabella Annesi-Maesano46, E.D. Bateman45, A. Ben Kheder47, Daniel A. Boakye48, J. Bouchard, Peter Burney18, William W. Busse49, Moira Chan-Yeung50, Niels H. Chavannes35, A.G. Chuchalin, William K. Dolen51, R. Emuzyte52, Lawrence Grouse53, Marc Humbert, C. M. Jackson54, Sebastian L. Johnston18, Paul K. Keith2, James P. Kemp27, J. M. Klossek55, Désirée Larenas-Linnemann55, Brian J. Lipworth54, Jean-Luc Malo24, Gailen D. Marshall56, Charles K. Naspitz57, K. Nekam, Bodo Niggemann58, Ewa Nizankowska-Mogilnicka59, Yoshitaka Okamoto60, M. P. Orru61, Paul Potter45, David Price62, Stuart W. Stoloff63, Olivier Vandenplas, Giovanni Viegi, Dennis M. Williams64 
Federal University of Bahia1, McMaster University2, University of Amsterdam3, National Institutes of Health4, Charité5, Catholic University of Cordoba6, University of Genoa7, Radboud University Nijmegen8, Transilvania University of Brașov9, Ghent University10, University of Tennessee Health Science Center11, University of Naples Federico II12, Laval University13, Universidade Federal de Minas Gerais14, University of Oslo15, University of Manchester16, Aarhus University17, Imperial College London18, Erasmus University Rotterdam19, George Washington University20, Seoul National University21, Medical University of Łódź22, Hai phong University Of Medicine and Pharmacy23, Université de Montréal24, Guangzhou Medical University25, University of South Florida26, University of California, San Diego27, University of California28, University of Chicago29, Monash University30, Teikyo University31, National and Kapodistrian University of Athens32, Nippon Medical School33, Sofia Medical University34, Leiden University35, Leiden University Medical Center36, University College London37, University of Manitoba38, University of Helsinki39, Finnish Institute of Occupational Health40, National University of Singapore41, Karolinska Institutet42, University of Minnesota43, Celal Bayar University44, University of Cape Town45, Pierre-and-Marie-Curie University46, Tunis University47, University of Ghana48, University of Wisconsin-Madison49, University of British Columbia50, Georgia Regents University51, Vilnius University52, University of Washington53, University of Dundee54, University of Poitiers55, University of Mississippi56, Federal University of São Paulo57, German Red Cross58, Jagiellonian University Medical College59, Chiba University60, American Pharmacists Association61, University of Aberdeen62, University of Nevada, Reno63, University of North Carolina at Chapel Hill64
01 Apr 2008-Allergy
TL;DR: The ARIA guidelines for the management of allergic rhinitis and asthma are similar in both the 1999 ARIA workshop report and the 2008 Update as discussed by the authors, but the GRADE approach is not yet available.
Abstract: Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

3,769 citations