Publications by authors named "Daan M Gerlag"

2 Publications

  • Page 1 of 1

FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis in rheumatoid arthritis.

Arthritis Res Ther 2013 ;15(6):R209

Introduction: The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients.

Methods: The levels of Flt3L in (paired) serum and synovial fluid (SF) were quantified by enzyme-link immunosorbent assay (ELISA). Expression of Flt3L and CD135 in paired peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) was quantified by fluorescence-activated cell sorting (FACS). The expression of Flt3L, CD135 and TNF-Converting Enzyme (TACE) in synovial tissues (STs) and in vitro polarized macrophages and monocyte-derived DCs (Mo-DCs) was assessed by quantitative PCR (qPCR). CD135 ST expression was evaluated by immunohistochemistry and TACE ST expression was assessed by immunofluorescence. Flt3L serum levels were assessed in RA patients treated with oral prednisolone or adalimumab.

Results: Flt3L levels in RA serum, SF and ST were significantly elevated compared to gout patients and healthy individuals (HI). RA SF monocytes, natural killer cells and DCs expressed high levels of Flt3L and CD135 compared to HI. RA ST CD68+ and CD163+ macrophages, CD55+ fibroblast-like synoviocytes (FLS), CD31+ endothelial cells or infiltrating monocytes and CD19+ B cells co-expressed TACE. IFN-γ-differentiated macrophages expressed higher levels of Flt3L compared to other polarized macrophages. Importantly, Flt3L serum levels were reduced by effective therapy.

Conclusions: The Flt3L/CD135 axis is active in RA patients and is responsive to both prednisolone and adalimumab treatment. Conceivably, this ligand receptor pair represents a novel therapeutic target.
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November 2014

[Vasculitis associated with Churg-Strauss syndrome].

Ned Tijdschr Geneeskd 2011 ;155:A2170

Academisch Medisch Centrum/Universiteit van Amsterdam, afd. Inwendige Geneeskunde en Klinische Immunologie en Reumatologie, Amsterdam, the Netherlands.

A 52-year-old man was admitted to hospital with abdominal pain, erythema and mild eosinophilia. Medical history revealed fatigue and dyspnoea on exertion after returning from the Gambia a year previously, and allergic rhinitis with nasal polyps that were surgically excised. Before a cause of the abdominal symptoms was determined he developed mononeuropathy, severe eosinophilia and arthralgia in combination with positive anti-neutrophil cytoplasmic antibodies (ANCA) against myeloperoxidase, which lead to the diagnosis of 'Churg-Strauss syndrome'. Despite treatment with high-dose corticosteroids (prednisone 1 mg/kg) his abdominal complaints intensified. A CT-scan of the abdomen showed a soft tissue mass around the caecum. Subsequent colonoscopy showed severe ulcerative lesions and signs of colonic ischemia. When PCR for cytomegalovirus appeared to be negative, treatment was intensified with cyclophosphamide 2 mg/kg, resulting in resolution of the abdominal complaints and healing of the ulcerative lesions in the colon.
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September 2011