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Witte T.,Klinik fur Immunologie und Rheumatologie
Zeitschrift fur Rheumatologie | Year: 2010

Sjögren's syndrome is a common autoimmune disorder. Several genetic risk factors such as STAT-4, ILT6 and the haplotype HLAB8/DR3 have been identified. In addition, there are environmental risk factors, possibly chronic viral infections. In the pathophysiology of Sjögren's syndrome T and B cells infiltrate the salivary and lacrimal glands. As a consequence of the destruction of glandular cells by cytotoxic T cells, production of cytokines and autoantibodies inhibiting glandular fu nction, the production of saliva and tears is decreased. The feeling of dry eyes and mouth is frequently not noticed by the patients. Therefore, Sjögren's syndrome should also be considered when extraglandular manifes-tations such as vasculitis, polyneuropathy or arthritis occur, even when the patients do not complain of dry eyes and mouth. Establishing the diagnosis of Sjögren's syndrome requires verification of reduced glandular function, for example using Schirmer's test and the Saxon test. The confirmation of Sjögren's syndrome as a cause of sicca syndrome is subsequently performed by the detection of autoantibodies against Ro (SS-A) and La (SS-B) and/or by a salivary gland biopsy. © Springer-Verlag 2009.

Classic polyarteritis nodosa and Kawasaki syndrome are vasculitic disorders of medium-sized arteries. Kawasaki syndrome is almost exclusively affecting children. The peak incidence of polyarteritis nodosa is at an age between 50 and 60 years. In this review, the pathophysiology, diagnostic procedures and treatment of the vasculitides are discussed. © Georg Thieme Verlag KG Stuttgart, New York.

Witte T.,Klinik fur Immunologie und Rheumatologie
Zeitschrift fur Rheumatologie | Year: 2016

In contrast to the other IgG subclasses, IgG4 does not bind to low affinity Fc receptors or activate the classical complement pathway. In addition, it is unstable and can dissociate into two hemimolecules; therefore, IgG4 most likely has an immunosuppressive role. On the other hand, there a few examples of an immunostimulatory role of IgG4 antibodies; therefore, the function of IgG4 in IgG4 related diseases is not yet entirely clear. The trigger factors of IgG4 related diseases (allergic or autoimmune) are still under debate. The activation of T helper (Th) 2 and regulatory T cells has been shown to be important in the pathophysiology of IgG4 related diseases as they produce cytokines which contribute to the formation of IgG4 and to fibrosis of various tissues. © 2016 Springer-Verlag Berlin Heidelberg

Baerlecken N.T.,Klinik fur Immunologie und Rheumatologie | Schmidt R.E.,Klinik fur Immunologie und Rheumatologie
Zeitschrift fur Rheumatologie | Year: 2012

Adult onset Still's disease (AOSD) with an incidence of 1-3 cases per 1 million belongs to the most difficult diagnosis of febrile diseases. The lack of biomarkers and its similarity to infectious and malignant and rheumatic diseases lead to a prolongation of its diagnosis. The following report focuses on providing an overview of the current knowledge of relevant symptoms and laboratory parameters for the diagnosis of AOSD and new treatment possibilities. © Springer-Verlag 2012.

Witte T.,Klinik fur Immunologie und Rheumatologie
Zeitschrift fur Rheumatologie | Year: 2014

Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the tear and salivary glands leading to dryness of the mouth and eyes. The awareness that extraglandular manifestations, such as polyneuropathy, arthritis or recurrent airway infections may indicate Sjögren's syndrome is important. In the diagnostic procedure, the tear and saliva production and antibodies against Sjögren's syndrome A (SS-A) and SS-B should be measured. A salivary gland biopsy should be performed when the diagnosis is not still clear. The therapy of oral and ocular dryness is mainly symptomatic whereas the treatment of extraglandular manifestations is based on experience with treatment of these manifestations in systemic lupus erythematosus (SLE). © 2014 Springer-Verlag.

Thomas R.,Klinik fur Immunologie und Rheumatologie | Matthias T.,Klinik fur Immunologie und Rheumatologie | Witte T.,Klinik fur Immunologie und Rheumatologie
Clinical Reviews in Allergy and Immunology | Year: 2010

Leukocyte immunoglobulin-like receptors (LILR) are a family of at least 13 receptors mainly expressed on lymphoid and myelomonocytic cells. They are involved in the activation of the immune system. Inhibitory LILR (termed LILRB) signal through immunoreceptor tyrosine-based inhibitory motives in the cytoplasmic domain, whereas LILRA with short cytoplasmic domains are stimulatory receptors. Polymorphisms and deletions of leukocyte immunoglobulin-like receptors have been shown to be associated with autoimmune disorders, and some of the receptors are involved in the generation of regulatory Tcells. Therefore, leukocyte immunoglobulin-like receptors may be central in the pathogenesis of autoimmunity. The data linking these receptors to autoimmune diseases is reviewed here. © Humana Press Inc. 2009.

Witte T.,Klinik fur Immunologie und Rheumatologie | Schulze-Koops H.,Ludwig Maximilians University of Munich
Arthritis Research and Therapy | Year: 2015

IgG4-related disease is rare, but a frequent differential diagnosis for malignant and for autoimmune diseases. Li and colleagues report the largest cohort of patients with IgG4-related sialadenitis. The observations reveal that the most important diagnostic step is obtaining biopsies. In addition, the IgG4 serum concentration may be a biomarker for the disease progression. © 2015 Witte and Schulze-Koops.

Background: The prognosis of rheumatoid arthritis has been substantially improved by the treatment with biologics; however, it is still unclear which combination of biological and conventional disease-modifying antirheumatic drugs (DMARDs) is optimal to achieve remission as in clinical trials biologics were mainly studied in combination with methotrexate or as monotherapy. There are, however data that the efficacy of tumor necrosis factor (TNF) inhibitors is better in combination with methotrexate, whereas the efficacy of tocilizumab is optimal even as a monotherapy. In this article the differing dependence of TNF inhibitors and of tocilizumab on the combination with methotrexate is explained from the viewpoint of an immunologist. Methods: A selective search and evaluation of the literature were carried out in relation to the mechanism of action of TNF inhibitors, tocilizumab and methotrexate in rheumatoid arthritis. Results and conclusions: Methotrexate mainly targets the activation of T and B lymphocytes and TNF inhibitors suppress monocytes and myeloid dendritic cells. Tocilizumab corrects the errant activation and differentiation of T and B lymphocytes and in addition inhibits monocytes, dendritic cells and neutrophils. Therefore, TNF inhibitors and methotrexate act optimally only in combination to exert an effect on all components of the cellular immune system in rheumatoid arthritis. In contrast, tocilizumab has a broad mode of action even in monotherapy. © 2013 Springer-Verlag Berlin Heidelberg.

Witte T.,Klinik fur Immunologie und Rheumatologie
Developments in Ophthalmology | Year: 2010

Establishing a diagnosis of Sjögren's syndrome (SS) has been difficult without sensitive laboratory markers, and in light of the non-specificity of the symptoms of dry eyes and mouth. Rather than complaints about dry eyes or dry mouth, objective symptoms and extraglandular manifestations should raise suspicion of SS. This evaluation requires the detection of antibodies against Ro (SSA) and La (SSB) or a pathologic salivary gland biopsy. Since an invasive biopsy is not always performed, further diagnostic markers are required. Recently antibodies against α-fodrin have been shown to be present in the majority of untreated patients, and can be used in the screening process of SS as an additional marker. © 2010 S. Karger AG, Basel.

Witte T.,Klinik fur Immunologie und Rheumatologie
Zeitschrift fur Rheumatologie | Year: 2016

Background: Intravenously administered immunoglobulins have multiple modes of action that are anti-inflammatory. They can therefore be beneficial in a number of autoimmune disorders. Objective: The aim of this article is to analyze and summarize studies on the administration of intravenous immunoglobulins in rheumatological diseases. Methods: A selective search and analysis of the literature was carried out related to the mode of action and efficacy of intravenous immunoglobulins in rheumatological diseases. Results and conclusion: Intravenous immunoglobulins have a broad mode of action and can therefore be beneficial in almost all autoimmune diseases. Conditions in which they are of special benefit include immunothrombopenia (ITP), Kawasaki disease and idiopathic inflammatory myopathies. In rare situations, they may also be indicated in systemic lupus erythematosus (SLE), Sjögren’s syndrome and neuropathies, catastrophic antiphospholipid syndrome (APS), scleroderma, antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, pyoderma gangrenosum and scleromyxedema. Severe adverse events are rare. In view of the high costs of the therapy, intravenous immunoglobulins are mostly applied in emergency situations, as salvage therapy when other standard therapies have failed or when severe infections are a contraindication to the administration of immunosuppressants. © 2016 Springer-Verlag Berlin Heidelberg

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