Author
Conny Höflich
Other affiliations: Humboldt University of Berlin, Humboldt State University
Bio: Conny Höflich is an academic researcher from Charité. The author has contributed to research in topics: Cytokine & Cytotoxic T cell. The author has an hindex of 18, co-authored 29 publications receiving 2263 citations. Previous affiliations of Conny Höflich include Humboldt University of Berlin & Humboldt State University.
Topics: Cytokine, Cytotoxic T cell, Interleukin 10, CD28, Immunodeficiency
Papers
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TL;DR: It is suggested that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
Abstract: Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-γ–deficient mice, or administration of IFN-γ at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-γ response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the β-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
797 citations
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TL;DR: It is postulated that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role, which helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies.
Abstract: Psoriasis is a chronic skin disease that affects about 1.5% of the Caucasian population and is characterized by typical macroscopic and microscopic skin alterations. Psoriatic lesions are sharply demarcated, red and slightly raised lesions with silver-whitish scales. The microscopic alterations of psoriatic plaques include an infiltration of immune cells in the dermis and epidermis, a dilatation and an increase in the number of blood vessels in the upper dermis, and a massively thickened epidermis with atypical keratinocyte differentiation. It is considered a fact that the immune system plays an important role in the pathogenesis of psoriasis. Since the early 1990s, it has been assumed that T1 cells play the dominant role in the initiation and maintenance of psoriasis. However, the profound success of anti-tumor necrosis factor-alpha therapy, when compared with T-cell depletion therapies, should provoke us to critically re-evaluate the current hypothesis for psoriasis pathogenesis. Recently made discoveries regarding other T-cell populations such as Th17 and regulatory T cells, dendritic cells, macrophages, the keratinocyte signal transduction and novel cytokines including interleukin (IL)-22, IL-23 and IL-20, let us postulate that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role. Our model helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies.
530 citations
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TL;DR: For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized and results demonstrated the independence of this test from flow cytometer and instrument settings.
Abstract: Background: Single-center trials have shown that monocytic HLA-DR is a good marker for monitoring the severity of temporary immunodepression after trauma, major surgery, or sepsis. A new test for measuring monocytic HLA-DR is now available.
Methods: We evaluated a new test reagent set for monocytic HLA-DR expression (BD Quantibrite™ HLA-DR/Monocyte reagent; Becton Dickinson) in single-laboratory and interlaboratory experiments, assessing preanalytical handling, lyse-no-wash (LNW) vs lyse-wash (LW) values, reference values, and the effect of use of different flow cytometers and different instrument settings on test variance.
Results: For preanalytical handling, EDTA anticoagulation, storage on ice as soon as possible, and staining within 4 h after blood collection gave results comparable to values obtained for samples analyzed immediately after collection (mean increase of ∼4% in monocytic HLA-DR). Comparison of LNW and LW revealed slightly higher results for LNW (∼18% higher for LNW compared with LW; r = 0.982). Comparison of different flow cytometers and instrument settings gave CVs <4%, demonstrating the independence of the test from these variables and suggesting that this method qualifies as a standardized test. CV values from the interlaboratory comparison ranged from 15% (blood sample unprocessed before transport) to 25% (stained and fixed before transport).
Conclusions: For the BD Quantibrite HLA-DR/Monocyte test, preanalytical handling is standardized. Single-laboratory results demonstrated the independence of this test from flow cytometer and instrument settings. Interlaboratory results showed greater variance than single-laboratory values. This interlaboratory variance was partly attributable to the influence of transport and can be reduced by optimization of transport conditions.
232 citations
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TL;DR: Screening for neutralizing anti-IFN-Gamma autoantibodies should supplement testing for IFN-gamma and IL-12 pathway defects in patients with recurrent infections with intracellular pathogens, especially with nontuberculous mycobacteria.
189 citations
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TL;DR: Intravenous methylprednisolone administration before hepatic resection significantly reduced systemic inflammatory cytokine release and the convalescence score and the length of hospital stay in the steroid group.
Abstract: Background/Purpose
Major abdominal surgery such as liver resection is associated with an excessive hyperinflammatory response and transient immunosuppression. We investigated the immunomodulating effect of preoperative pulse administration of high-dose methylprednisolone in patients undergoing hepatic resection without pedicle clamping.
78 citations
Cited by
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TL;DR: The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
Abstract: This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
2,125 citations
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TL;DR: Gaining a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.
Abstract: Immunity and inflammation are key elements of the pathobiology of stroke, a devastating illness second only to cardiac ischemia as a cause of death worldwide. The immune system participates in the brain damage produced by ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that promotes fatal infections that threaten the survival of people after stroke. Inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion to the late regenerative processes underlying post-ischemic tissue repair. Recent developments have revealed that stroke engages both innate and adaptive immunity. But adaptive immunity triggered by newly exposed brain antigens does not have an impact on the acute phase of the damage. Nevertheless, modulation of adaptive immunity exerts a remarkable protective effect on the ischemic brain and offers the prospect of new stroke therapies. As immunomodulation is not devoid of deleterious side effects, a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.
1,949 citations
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University of Paris1, Rockefeller University2, French Institute of Health and Medical Research3, National Institutes of Health4, University of Tartu5, Lyon College6, Tartu University Hospital7, Utrecht University8, Vita-Salute San Raffaele University9, Yale University10, Pasteur Institute11, Collège de France12, University of Amsterdam13, McGill University Health Centre14, Garvan Institute of Medical Research15, University of New South Wales16, Ghent University Hospital17, University of Barcelona18, University of Vic19, Catalan Institution for Research and Advanced Studies20, Science for Life Laboratory21, Karolinska University Hospital22, Howard Hughes Medical Institute23, Aarhus University24, Aarhus University Hospital25, University of Milano-Bicocca26, University of Lorraine27, Karolinska Institutet28, Haukeland University Hospital29, University of Bergen30, Canadian Real Estate Association31, University of Brescia32, University of Pavia33
TL;DR: A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested.
Abstract: Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
1,913 citations
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TL;DR: Ustekinumab seems to be efficacious for the treatment of moderate-to-severe psoriasis; dosing every 12 weeks maintains efficacy for at least a year in most patients.
1,715 citations
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TL;DR: The diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections and had a higher positive likelihood ratio and lower negative likelihood ratio than didCRP markers in both groups.
Abstract: A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.
1,590 citations