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Article ; Online: Twee patiënten met kattenkrabziekte.

de Leijer, Jan F / Stutvoet, Thijs S / Huugen, Dennis

2023 Volume 167

Abstract: Background: Cat scratch disease (CSD) is caused by Bartonella henselae infection. CSD is usually characterized by self-limiting regional lymphadenopathy. However, sometimes CSD presents as a disseminated disease with multiple organ involvement.: Case ... ...

Title translation	Two patients with cat scratch disease.
Abstract	Background: Cat scratch disease (CSD) is caused by Bartonella henselae infection. CSD is usually characterized by self-limiting regional lymphadenopathy. However, sometimes CSD presents as a disseminated disease with multiple organ involvement. Case descriptions: We describe two patients with CSD. Patient A, an 18-year old woman, was referred because of fatigue, a subfebrile temperature and axillary lymphadenopathy. Patient B, a 50-year old man, visited the emergency ward with fever, back pain and painful inguinal lymphadenopathy. MRI showed osteitis of vertebrae and hepatic abcesses. In both patients symptoms started after being scratched by a cat and both were tested positive for infection with Bartonella henselae. Patient B was treated with antibiotics. Both patients made a full recovery. Conclusion: Recent contact with a cat in a patient with unexplained fever and lymphadenopathy raises the possibility of CSD. Diagnosis can be confirmed by serologic testing, histopathology or PCR. Antimicrobial treatment must be considered in all cases.
MeSH term(s)	Humans ; Cat-Scratch Disease/complications ; Cat-Scratch Disease/diagnosis ; Cat-Scratch Disease/drug therapy ; Bartonella henselae ; Anti-Bacterial Agents/therapeutic use ; Lymphadenopathy/diagnosis ; Lymphadenopathy/etiology ; Liver
Chemical Substances	Anti-Bacterial Agents
Language	Dutch
Publishing date	2023-03-08
Publishing country	Netherlands
Document type	Case Reports ; English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Injection of ANCA-No Neutrophils, No Glomerular Damage: The Role of Neutrophils in the Induction of Glomerulonephritis by Anti-Myeloperoxidase Antibodies. Am J Pathol 167: 39-45, 2005.

Xiao, H / Heeringa, P / Liu, Z / Huugen, D / Hu, P / Maeda, N / Falk, R J / Jennette, J C

Journal of the American Society of Nephrology : JASN

2023 Volume 16, Issue 9, Page(s) 2521–2527

Language	English
Publishing date	2023-03-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/01.asn.0000926740.18373.6b
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Zs.A 3344: Show issues

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Article ; Online: Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients.

Rutgers, Abraham / Westerweel, Peter E / van der Holt, Bronno / Postma, Simone / van Vonderen, Marit G A / Piersma, Djura P / Postma, Douwe / van den Berge, Maarten / Jong, Eefje / de Vries, Marten / van der Burg, Leonie / Huugen, Dennis / van der Poel, Marjolein / Kampschreur, Linda M / Nijland, Marcel / Strijbos, Jaap H / Tamminga, Menno / Mutsaers, Pim G N J / Schol-Gelok, Suzanne /

Dijkstra-Tiekstra, Margriet / Sidorenkov, Grigory / Vincenten, Julien / van Geffen, Wouter H / Knoester, Marjolein / Kosterink, Jos / Gans, Reinold / Stegeman, Coen / Huls, Gerwin / van Meerten, Tom

PloS one

2022 Volume 17, Issue 8, Page(s) e0271807

Abstract: Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.: Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with ... ...

Abstract	Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. Results: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). Conclusions: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone. Trial registration: https://www.trialregister.nl/trial/8504.
MeSH term(s)	Aged ; Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy ; Dexamethasone/therapeutic use ; Female ; Humans ; Male ; Oxygen ; Respiration, Artificial ; SARS-CoV-2 ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal, Humanized ; Dexamethasone (7S5I7G3JQL) ; tocilizumab (I031V2H011) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-08-12
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0271807
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Article ; Online: Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing.

Kessler, Nina / Viehmann, Susanne F / Krollmann, Calvin / Mai, Karola / Kirschner, Katharina M / Luksch, Hella / Kotagiri, Prasanti / Böhner, Alexander M C / Huugen, Dennis / de Oliveira Mann, Carina C / Otten, Simon / Weiss, Stefanie A I / Zillinger, Thomas / Dobrikova, Kristiyana / Jenne, Dieter E / Behrendt, Rayk / Ablasser, Andrea / Bartok, Eva / Hartmann, Gunther /

Hopfner, Karl-Peter / Lyons, Paul A / Boor, Peter / Rösen-Wolff, Angela / Teichmann, Lino L / Heeringa, Peter / Kurts, Christian / Garbi, Natalio

The Journal of experimental medicine

2022 Volume 219, Issue 10

Abstract: Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development of targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic ... ...

Abstract	Autoimmune vasculitis is a group of life-threatening diseases, whose underlying pathogenic mechanisms are incompletely understood, hampering development of targeted therapies. Here, we demonstrate that patients suffering from anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) showed increased levels of cGAMP and enhanced IFN-I signature. To identify disease mechanisms and potential therapeutic targets, we developed a mouse model for pulmonary AAV that mimics severe disease in patients. Immunogenic DNA accumulated during disease onset, triggering cGAS/STING/IRF3-dependent IFN-I release that promoted endothelial damage, pulmonary hemorrhages, and lung dysfunction. Macrophage subsets played dichotomic roles in disease. While recruited monocyte-derived macrophages were major disease drivers by producing most IFN-β, resident alveolar macrophages contributed to tissue homeostasis by clearing red blood cells and limiting infiltration of IFN-β-producing macrophages. Moreover, pharmacological inhibition of STING, IFNAR-I, or its downstream JAK/STAT signaling reduced disease severity and accelerated recovery. Our study unveils the importance of STING/IFN-I axis in promoting pulmonary AAV progression and identifies cellular and molecular targets to ameliorate disease outcomes.
MeSH term(s)	Animals ; Interferon Type I ; Lung ; Macrophages ; Membrane Proteins/metabolism ; Mice ; Nucleic Acids ; Nucleotidyltransferases ; Vasculitis
Chemical Substances	Interferon Type I ; Membrane Proteins ; Nucleic Acids ; Sting1 protein, mouse ; Nucleotidyltransferases (EC 2.7.7.-)
Language	English
Publishing date	2022-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20220759
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Ua VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Correction: Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing.

Hopfner, Karl-Peter / Lyons, Paul A / Boor, Peter / Rösen-Wolff, Angela / Teichmann, Lino L / Heeringa, Peter / Kurts, Christian / Garbi, Natalio

The Journal of experimental medicine

2022 Volume 219, Issue 12

Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Published Erratum
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.2022075911022022c
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Article ; Online: TNF-alpha bioactivity-inhibiting therapy in ANCA-associated vasculitis: clinical and experimental considerations.

Huugen, Dennis / Tervaert, Jan Willem Cohen / Heeringa, Peter

Clinical journal of the American Society of Nephrology : CJASN

2006 Volume 1, Issue 5, Page(s) 1100–1107

Abstract: Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing crescentic glomerulonephritis, and Churg-Strauss syndrome are associated with the presence of ANCA with specificity for myeloperoxidase or proteinase 3. Current therapy consists ... ...

Abstract	Wegener's granulomatosis, microscopic polyangiitis, idiopathic necrotizing crescentic glomerulonephritis, and Churg-Strauss syndrome are associated with the presence of ANCA with specificity for myeloperoxidase or proteinase 3. Current therapy consists mainly of corticosteroids and cyclophosphamide, but because this treatment regimen is associated with considerable morbidity, other treatment modalities remain desirable. There is compelling evidence that TNF-alpha plays an important role in the pathogenesis of ANCA-associated vasculitis. Consequently, inhibition of TNF-alpha bioactivity potentially results in attenuation of disease. This review discusses whether TNF-alpha bioactivity-inhibiting drugs are useful in the treatment of ANCA-associated vasculitis. The results of in vitro and in vivo experiments, as well as clinical studies, are evaluated. Although the importance of TNF-alpha during lesion development is evident, clinical trials that use TNF-alpha blockers in patients with ANCA-associated vasculitis give mixed results. Importantly, in a large-scale, randomized trial, treatment with etanercept was found not to be effective and resulted in an excess of treatment-related morbidity. It remains to be investigated whether inhibition of TNF-alpha bioactivity is effective in a subgroup of patients.
MeSH term(s)	Animals ; Antibodies, Antineutrophil Cytoplasmic/blood ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Churg-Strauss Syndrome/drug therapy ; Churg-Strauss Syndrome/immunology ; Churg-Strauss Syndrome/metabolism ; Disease Models, Animal ; Etanercept ; Glomerulonephritis/drug therapy ; Glomerulonephritis/immunology ; Glomerulonephritis/metabolism ; Granulomatosis with Polyangiitis/drug therapy ; Granulomatosis with Polyangiitis/immunology ; Granulomatosis with Polyangiitis/metabolism ; Humans ; Immunoglobulin G/adverse effects ; Immunoglobulin G/therapeutic use ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Infliximab ; Receptors, Tumor Necrosis Factor/therapeutic use ; Treatment Outcome ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Antibodies, Monoclonal ; Immunoglobulin G ; Immunosuppressive Agents ; Receptors, Tumor Necrosis Factor ; Tumor Necrosis Factor-alpha ; Infliximab (B72HH48FLU) ; Etanercept (OP401G7OJC)
Language	English
Publishing date	2006-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2226665-3
ISSN	1555-905X ; 1555-9041
ISSN (online)	1555-905X
ISSN	1555-9041
DOI	10.2215/CJN.02181205
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Zs.A 6584: Show issues

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Article: Anti-neutrophil cytoplasmic autoantibodies and leukocyte-endothelial interactions: a sticky connection?

Heeringa, Peter / Huugen, Dennis / Tervaert, Jan Willem Cohen

Trends in immunology

2005 Volume 26, Issue 11, Page(s) 561–564

Abstract: Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificity for myeloperoxidase (MPO) or proteinase 3 (Pr3) are associated with systemic small-vessel vasculitides (SVV). Detection of ANCA is an established clinical tool in disease diagnosis and ... ...

Abstract	Anti-neutrophil cytoplasmic autoantibodies (ANCA) with specificity for myeloperoxidase (MPO) or proteinase 3 (Pr3) are associated with systemic small-vessel vasculitides (SVV). Detection of ANCA is an established clinical tool in disease diagnosis and monitoring. Based on clinical and in vitro experimental evidence, a pathogenic role for ANCA has long been suspected, however, in vivo models in which causality can be tested have been lacking. Recently, an exciting novel rat model of MPO-ANCA-associated vasculitis has been described, which provides compelling evidence that MPO-ANCA are a primary pathogenic factor in SVV by augmenting leukocyte-endothelial interactions and vascular wall damage.
MeSH term(s)	Animals ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Cell Adhesion/immunology ; Disease Models, Animal ; Endothelial Cells/immunology ; Humans ; Leukocytes/immunology ; Models, Immunological ; Myeloblastin ; Peroxidase/immunology ; Rats ; Serine Endopeptidases/immunology
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Peroxidase (EC 1.11.1.7) ; Serine Endopeptidases (EC 3.4.21.-) ; Myeloblastin (EC 3.4.21.76)
Language	English
Publishing date	2005-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2036831-8
ISSN	1471-4981 ; 1471-4906
ISSN (online)	1471-4981
ISSN	1471-4906
DOI	10.1016/j.it.2005.08.010
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Zs.A 1601: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Advantages and limitations of (non-)myeloablative allogeneic stem cell transplantation.

Huugen, D / Schouten, H C / Bos, G M J

The Netherlands journal of medicine

2002 Volume 60, Issue 4, Page(s) 162–169

Abstract: Allogeneic stem cell transplantation (allo-SCT) is the treatment of choice for a variety of malignant diseases, not only as a method to regain haematopoiesis after myeloablative therapy, but also for its apparent antitumour effect. However, treatment- ... ...

Abstract	Allogeneic stem cell transplantation (allo-SCT) is the treatment of choice for a variety of malignant diseases, not only as a method to regain haematopoiesis after myeloablative therapy, but also for its apparent antitumour effect. However, treatment-related morbidity and mortality are considerable. A potential way to overcome this problem is by decreasing the intensity of chemotherapy and/or radiotherapy given prior to transplantation. This reduced-intensity conditioning regimen is the basis of non-myeloablative allo-SCT (also referred to as mini SCT), a new treatment modality that relies more heavily on the antitumour effect exerted by the donor cells than on the antitumour effect of the conditioning therapy. The aim of this article is to place the concept of non-myeloablative SCT in a historical context and to discuss the advantages and disadvantages of regular myeloablative SCT compared with non-myeloablative SCT. Furthermore, human trials regarding non-myeloablative SCT are reviewed, and several experimental techniques are discussed that aim to augment the antitumour effect of an allogeneic graft.
MeSH term(s)	Animals ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Histocompatibility ; Humans ; Transplantation Conditioning/adverse effects ; Transplantation Conditioning/methods ; Transplantation, Homologous
Language	English
Publishing date	2002-05
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	193149-0
ISSN	1872-9061 ; 0300-2977
ISSN (online)	1872-9061
ISSN	0300-2977
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Article: Antineutrophil cytoplasmic autoantibodies and pathophysiology: new insights from animal models.

Huugen, Dennis / Tervaert, Jan Willem Cohen / Heeringa, Peter

Current opinion in rheumatology

2003 Volume 16, Issue 1, Page(s) 4–8

Abstract: Purpose of review: Since the discovery of antineutrophil cytoplasmic autoantibodies (ANCA) and their association with the occurrence of several types of small-vessel vasculitis, a causal relation between the two has been suggested. Various in vitro and ... ...

Abstract	Purpose of review: Since the discovery of antineutrophil cytoplasmic autoantibodies (ANCA) and their association with the occurrence of several types of small-vessel vasculitis, a causal relation between the two has been suggested. Various in vitro and in vivo experimental data provide indirect evidence in support of this view. This article comprises a review of the animal models that have been used to investigate the pathogenesis of ANCA-associated vasculitis, and focuses on recent developments in this field. Recent findings: Xiao et al. provide definite proof of the pathogenic potential of ANCA in a novel mouse model of myeloperoxidase (MPO)-ANCA-associated vasculitis, in which transfer of splenocytes or IgG from MPO-/- mice immunized with murine MPO, to naive wild-type or Rag2-/- (lacking mature B and T lymphocytes) mice causes a disease remarkably similar to its human counterpart. In addition, preliminary studies by Smyth et al. show that immunization of Wistar Kyoto rats with human MPO induces antihuman MPO antibodies that cross-react with rat MPO, as well as a disease closely resembling human small-vessel vasculitis. Another murine ANCA model is the SCG/Kj mouse. A recent publication by Neumann et al., however, puts an important limitation on the use of this mouse model for the study of ANCA-associated vasculitis, demonstrating multiple immune complex deposits in the spontaneously occurring vascular lesions. SUMMARY Recently developed animal models of MPO-ANCA-associated vasculitis convincingly demonstrate that MPO-ANCA are pathogenic. Whether similar strategies can be used to develop an appropriate model for proteinase 3-ANCA-associated vasculitis remains to be investigated.
MeSH term(s)	Animals ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Disease Models, Animal ; Mice ; Rats ; T-Lymphocytes/immunology ; Vasculitis/immunology ; Vasculitis/physiopathology
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic
Language	English
Publishing date	2003-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1045317-9
ISSN	1531-6963 ; 1040-8711
ISSN (online)	1531-6963
ISSN	1040-8711
DOI	10.1097/00002281-200401000-00003
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Article: The role of neutrophils in the induction of glomerulonephritis by anti-myeloperoxidase antibodies.

Xiao, Hong / Heeringa, Peter / Liu, Zhi / Huugen, Dennis / Hu, Peiqi / Maeda, Nobuyo / Falk, Ronald J / Jennette, J Charles

The American journal of pathology

2005 Volume 167, Issue 1, Page(s) 39–45

Abstract: In humans, circulating anti-neutrophil cytoplasm autoantibodies (ANCAs) with specificity for myeloperoxidase (MPO) are strongly associated with the development of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN). In mice, we have ... ...

Abstract	In humans, circulating anti-neutrophil cytoplasm autoantibodies (ANCAs) with specificity for myeloperoxidase (MPO) are strongly associated with the development of pauci-immune necrotizing and crescentic glomerulonephritis (NCGN). In mice, we have demonstrated that intravenous injection of mouse antibodies specific for mouse MPO induces NCGN that closely mimics the human disease. We now report that the development of NCGN in this experimental model is accompanied by glomerular accumulation of neutrophils and macrophages. Neutrophil infiltration was most conspicuous at sites of glomerular necrosis and crescent formation, with macrophages also most numerous in crescents. Lymphocytes, however, were sparse in acute lesions. Importantly, mice that were depleted of circulating neutrophils with NIMP-R14 rat monoclonal antibodies were completely protected from anti-MPO IgG-induced NCGN. These findings provide direct evidence that neutrophils play a major role in the pathogenesis of anti-MPO-induced NCGN in this animal model and implicate neutrophils in the induction of human ANCA disease. This raises the possibility that therapeutic strategies to reduce circulating neutrophils could be beneficial to patients with ANCA-induced NCGN.
MeSH term(s)	Animals ; Antibodies, Antineutrophil Cytoplasmic/immunology ; Disease Models, Animal ; Glomerulonephritis/immunology ; Glomerulonephritis/pathology ; Macrophages/immunology ; Mice ; Neutrophil Activation/immunology ; Neutrophils/immunology ; Peroxidase/immunology
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Peroxidase (EC 1.11.1.7)
Language	English
Publishing date	2005-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/S0002-9440(10)62951-3
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