Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed. Our understanding of its activity is complicated by the possibility that TIM-1 possesses multiple and diverse binding partners. In order to delineate the function of TIM-1, we generated monoclonal antibodies directed to a cleft formed within the IgV domain of TIM-1. We have shown here that antibodies that bind to this defined cleft antagonize TIM-1 binding to specific ligands and cells. Notably, these antibodies exhibited therapeutic activity in a humanized SCID model of experimental asthma, ameliorating inflammation, and airway hyperresponsiveness. Further experiments demonstrated that the effects of the TIM-1-specific antibodies were mediated via suppression of Th2 cell proliferation and cytokine production. These results demonstrate that modulation of the TIM-1 pathway can critically influence activated T cells in a humanized disease model, suggesting that TIM-1 antagonists may provide potent therapeutic benefit in asthma and other immune-mediated disorders.

Difficult-to-treat asthma (DTA) represents a heterogeneous subgroup of asthma. Up to now, the lack of specific diagnosis not only complicates appropriate specification and control of asthma, but also makes targeted research difficult. The aim of this study is to categorize this heterogeneous group of DTA patients (n ¼ 27; referring to the GINA guidelines) based on the distinct leucocyte redistribution (LR) after glucocorticoid (GC) treatment. Furthermore, the effect of adjuvant therapies was investigated for its impact on LR. The frequency of CD3þ and NK cells was analysed in peripheral blood before and 3 h after systemic GC treatment, along with the markers of activation HLA-DR and CD25. Within 3 h of GC administration, a significant average decrease of 16% in CD3 þ CD4 þ (P 0.001) and a 12% increase in NK-cell frequency (P 0.001) clearly distinguished two groups of patients: LRresponsive and LR-unresponsive patients. The CD3 þ CD8þ T-cell number and activation marker remained unchanged. Patients who received adjuvant therapy, such as methotrexate or interferon-a, because of poor clinical response to GC showed an LR similar to that showed by responsive patients. DTA patients comprise at least two immunologically distinct groups: patients showing an immediate decrease in CD3 þ CD4 þ T cells and an increase in NK cells following GC administration and patients lacking an immediate change. Analysis of LR not only may allow the identification of immunologic steroid resistance, but also may be of value for immunologic determination of effective steroid doses.

ABPA is the most common allergic bronchopulmonary mycosis in humans. The diagnosis of the complex disease is based on defined criteria. Five clinical stages of ABPA were proposed. The extend of the defined criteria varies in the different stages, thus making diagnosis difficult. Particularly the discrimination of ABPA in remission stage (stage II) and allergic asthma with A--sensitisation may be an important problem. Early diagnosis in stages without persistent changes of bronchial wall and lung parenchyma is needed to prevent severe end stages of ABPA. The up to now widely used commercial (crude) allergen extracts for in vitro and in vivo diagnosis show batch to batch variation, insufficient standardization and lack of reproducibility. Potentials and limitations of routine diagnostic procedures in ABPA are described. The production of a panel of recombinant allergens of A. fumigatus and their evaluation for in vivo and particularly in vitro use has brought an important step forward in the early and precise diagnosis of ABPA. A panel of recombinant allergens is now available for routine assay in CAP-System.

No abstract

Allergische Rhinokonjunktivitis, allergisches Asthma bronchiale und atopisches Ekzem sind die häufigsten allergischen Erkrankungen mit enormer sozio-ökonomischer Bedeutung. Die Diagnose basiert auf der bewährten Mehrstufendiagnostik. In der Behandlung kommt neben der Allergenkarenz und der Pharmakotherapie der spezifischen Immuntherapie mit neuen Produkten und neuen Applikationsformen zunehmende Bedeutung zu. Der Einsatz des Anti-IgE-Antikörpers Omalizumab ist zurzeit auf Patienten mit schwergradiger Verlaufsform des allergischen Asthma bronchiale zu beschränken.kung auf die Entwicklung allergischer Krankheiten zu haben. Neuere Daten weisen auch auf einen möglichen Schutzeffekt von Bauernmilch hin. Kinder, die vor dem ersten Geburtstag regelmäßig Kuhmilch direkt vom Hof getrunken haben, erkrankten weniger häufig an Asthma bronchiale und Heuschnupfen.