A novel molecular disease classifier for psoriasis and eczema

Garzorz‐Stark N, Krause L, Lauffer F, Atenhan A, Thomas J, Stark SP, Franz R, Weidinger S, Balato A, Nikola S, Mueller NS, Theis FJ, Ring J, Schmidt‐Weber CB, Biedermann T, Eyerich S, Eyerich K.

Experimental Dermatology, 25(10), 2016.

Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin‐embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field.

Eczema or psoriasis? A special challenge in occupational dermatology

Weisshaar, E, Garzorz‐Stark N, Eyerich K.

Dermatologie in Beruf und Umwelt, 66(3), 2018.

In daily dermatological practice as in occupational dermatology, patients with psoriasis vulgaris and atopic eczema are seen frequently. These diseases may appear very similar in terms of morphology. Thus, the differentiation between nummular eczema and psoriatic plaque may form a challenge, equally between hand eczema and psoriasis manuum. So far, diagnostic classification was based on patient and family medical history, comorbidities, onset and course of disease, morphology and localization, and diagnostic tests such as allergy tests and dermatopathology. Especially the latter was not yet able to allow helpful classification. A new molecular disease classifier based on the expression of the genes NOS2 and CCL27 in lesional skin has been developed that improves the diagnostic classification of diseases such as eczema and psoriasis. This test is reliable in classical variations as well as in subtypes of the diseases. Our paper presents

first experiences with this molecular classifier in a group of patients attending a clinic for occupational skin diseases. We hope that this classifier may in future be applied as a routine test in diagnostics and may possibly even allow prognostics about clinical course, comorbidities and optimal therapy. Being now a first simple diagnostic test for the differentiation between psoriasis and eczema, this classifier is most likely to achieve an important prospective role in times of personalized medicine in occupational dermatology.

Personalisierte Medizin im Bereich entzündlicher Hauterkrankungen

Garzorz‐Stark N, Eyerich K.

Der Hautarzt, 70(1), 2019.

Obwohl zunehmend wirksame zielgerichtete Systemtherapien für die Behandlung chronisch entzündlicher Hauterkrankungen zur Verfügung stehen, sind diese nur unzureichend diagnostiziert und therapiert. Dies liegt daran, dass – basierend auf einer überholten Ontologie – die Komplexität und Heterogenität der Erkrankungen nicht ausreichend berücksichtigt wird. So stehen jenseits konventioneller Verfahren keine Biomarker in der Routineversorgung zur Verfügung. Diese sind jedoch dringend vonnöten, um personalisierte Medizin auch für den Formenkreis entzündlicher Hauterkrankungen zu implementieren.

Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema.

Quaranta M, Knapp B, Garzorz N, Mattii M, Pullabhatla V, Pennino D, Andres C, Traidl-Hoffmann C, Cavani A, Theis FJ, Ring J, Schmidt-Weber CB, Eyerich S, Eyerich K.

Previous attempts to gain insight into the pathogenesis of psoriasis and eczema by comparing their molecular signatures were hampered by the high interindividual variability of those complex diseases. In patients affected by both psoriasis and nonatopic or atopic eczema simultaneously (n = 24), an intraindividual comparison of the molecular signatures of psoriasis and eczema identified genes and signaling pathways regulated in common and exclusive for each disease across all patients. Psoriasis-specific genes were important regulators of glucose and lipid metabolism, epidermal differentiation, as well as immune mediators of T helper 17 (TH17) responses, interleukin-10 (IL-10) family cytokines, and IL-36. Genes in eczema related to epidermal barrier, reduced innate immunity, increased IL-6, and a TH2 signature. Within eczema subtypes, a mutually exclusive regulation of epidermal differentiation genes was observed. Furthermore, only contact eczema was driven by inflammasome activation, apoptosis, and cellular adhesion. On the basis of this comprehensive picture of the pathogenesis of psoriasis and eczema, a disease classifier consisting of NOS2 and CCL27 was created. In an independent cohort of eczema (n = 28) and psoriasis patients (n = 25), respectively, this classifier diagnosed all patients correctly and also identified initially misdiagnosed or clinically undifferentiated patients.

Centrifugal microfluidic platforms: advanced unit operations and applications.

Strohmeier O, Keller M, Schwemmer F, Zehnle S, Mark D, von Stetten F, Zengerle R, Paust N.

Chemical Society Reviews, 44(17):6187-6229, 2015

Centrifugal microfluidics has evolved into a mature technology. Several major diagnostic companies either have products on the market or are currently evaluating centrifugal microfluidics for product development. The fields of application are widespread and include clinical chemistry, immunodiagnostics and protein analysis, cell handling, molecular diagnostics, as well as food, water, and soil analysis. Nevertheless, new fluidic functions and applications that expand the possibilities of centrifugal microfluidics are being introduced at a high pace. In this review, we first present an up-to-date comprehensive overview of centrifugal microfluidic unit operations. Then, we introduce the term "process chain" to review how these unit operations can be combined for the automation of laboratory workflows. Such aggregation of basic functionalities enables efficient fluidic design at a higher level of integration. Furthermore, we analyze how novel, ground-breaking unit operations may foster the integration of more complex applications. Among these are the storage of pneumatic energy to realize complex switching sequences or to pump liquids radially inward, as well as the complete pre-storage and release of reagents. In this context, centrifugal microfluidics provides major advantages over other microfluidic actuation principles: the pulse-free inertial liquid propulsion provided by centrifugal microfluidics allows for closed fluidic systems that are free of any interfaces to external pumps. Processed volumes are easily scalable from nanoliters to milliliters. Volume forces can be adjusted by rotation and thus, even for very small volumes, surface forces may easily be overcome in the centrifugal gravity field which enables the efficient separation of nanoliter volumes from channels, chambers or sensor matrixes as well as the removal of any disturbing bubbles. In summary, centrifugal microfluidics takes advantage of a comprehensive set of fluidic unit operations such as liquid transport, metering, mixing and valving. The available unit operations cover the entire range of automated liquid handling requirements and enable efficient miniaturization, parallelization, and integration of assays.

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