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K Warnatz

Publications and source records attributed to K Warnatz.

At least 19 recordsLinked to original sources

Influence of corticosteroid treatment on MRI findings in giant cell arteritis.

Giant cell arteritis (GCA) remains a diagnostic challenge. With the use of a high-resolution MRI protocol, visualization of the superficial cranial arteries is feasible and mural inflammation can be assessed noninvasively. Until today, it is not known how soon inflammatory signals in diagnostic MR imaging vanish after initiation of treatment. Here, we report sequential MR imaging findings during the initial weeks of corticosteroid treatment in a 79-year-old female patient with histologically proven GCA. Mural inflammatory changes decreased within the first 2 weeks and have almost entirely vanished after 2 1/2 months of continued treatment. Moreover, MR angiography revealed sequential stenoses of the subclavian artery, which improved in variable extent with some residuals despite high dose steroid medication. This report underlines the value of high-resolution MRI in diagnosis and follow-up of GCA and illustrates the potential of MRI to detect and monitor intra- and extra-cranial involvement patterns of GCA in high detail.

Adrenal Cortex Hormones↗

Analgesic and disease modifying effects of interferential current in psoriatic arthritis.

Interferential current (IFC) was suggested to improve the skin manifestations of psoriasis vulgaris, possibly by enhancing the intracellular concentration of cyclic AMP. We assessed the efficacy of IFC on psoriatic arthritis (PsA). Nine consecutive patients were analyzed at baseline and after 16 weeks of IFC therapy. Bipolar IFC was applied twice daily to hands, feet plus all affected joints. IFC improved SF-36 assessed body pain, but not other SF-36 subscales. Morning stiffness, tender joint counts, and physician assessed disease activity improved. In contrast, visual analogue scale assessed pain, CRP and ESR measurements were unchanged. MRI of the most affected hand or foot documented a tendency towards worsened tendinitis, soft tissue swelling, and new joint space narrowing and erosions. Bone scintigraphy showed a trend towards deterioration. New joints became inflamed within treated sites. Thus IFC has analgesic effects in PsA, but does not have a satisfactory disease modifying effect.

Adult↗

Assessment of the cranial involvement pattern of giant cell arteritis with 3T magnetic resonance imaging.

OBJECTIVE: To noninvasively determine the involvement pattern of the cranial arteries in giant cell arteritis (GCA), with high-resolution magnetic resonance imaging (MRI). METHODS: The superficial cranial arteries of 21 patients with suspected GCA were examined using a 3T high-field MRI scanner. Postcontrast T1-weighted spin-echo images were acquired with submillimeter spatial resolution, to assess mural thickness and lumen diameter of the major cranial arteries on both sides of the head. In all cases, MRI results were compared with findings of clinical examination and laboratory tests. In addition, temporal artery biopsy specimens from 10 patients were examined by histology. RESULTS: MRI sharply revealed all of the major superficial cranial arteries, allowing for an evaluation of their lumen and vessel wall. Nine of the 21 patients were diagnosed as having GCA according to the criteria of the American College of Rheumatology. In all of these patients with clinically diagnosed GCA, multiple cranial arteries showed signs of inflammation on MRI. In 1 patient, the occipital arteries were inflamed, while the temporal arteries were spared. CONCLUSION: Postcontrast high-resolution MRI visualizes the major cranial arteries on both sides of the head within a single examination. The cranial involvement pattern in GCA can be assessed precisely and noninvasively. In the majority of GCA patients, several cranial arteries were affected simultaneously, with a predominance of involvement of the frontal branch of the superficial temporal artery. Inflammation of the occipital arteries, with sparing of the temporal arteries, was also encountered.

Aged↗

Measurement of peripheral B cell subpopulations in common variable immunodeficiency (CVID) using a whole blood method.

Recent reports have described reduced populations of CD27+ memory B cells and increased percentages of undifferentiated B cells in peripheral blood of patients with common variable immunodeficiency (CVID). This work has prompted two attempts to classify CVID based on rapid flow cytometric quantification of peripheral blood memory B cells and immature B cells. Evidence to support the hypothesis that such in vitro B cell classification systems correlate with clinical subtypes of CVID is being sought. For the classification to be useful in routine diagnosis, it is important that the flow cytometric method can be used without prior separation of peripheral blood mononuclear cells (PBMC). We have examined 23 CVID patients and 24 controls, using both PBMC and whole blood, and find an excellent correlation between these methods. The reproducibility of the method was excellent. We classified the CVID patients by all three of the existing classifications, including secretion of immunoglobulin by B cells in vitro as described by Bryant, as well as the more recent flow cytometric classification methods. Only one patient changed classification as a result of using whole blood.

Adolescent↗

Immunosuppressive treatment of chronic periaortitis: a retrospective study of 20 patients with chronic periaortitis and a review of the literature.

BACKGROUND: Retroperitoneal fibrosis (RPF) and inflammatory aneurysm of the abdominal aorta (IAAA) are regarded as two manifestations of the same disease, termed "chronic periaortitis". OBJECTIVE: To determine the optimal therapeutic and diagnostic approaches to IAAA. METHODS: The outcome of medical immunosuppressive and surgical treatment of 20 patients was examined. Measurements of the C reactive protein (CRP) were compared with contrast enhanced imaging studies in the follow up of the patients. RESULTS: The diameter of the periaortic mantle and its contrast enhancement improved in 13/15 (87%) patients given immunosuppressive treatment for a period of more than 6 months. Strong contrast enhancement was associated with a substantial rise in CRP, but no correlation between the CRP value and thickness of the fibrotic mass was found, even at intraindividual follow up. CONCLUSIONS: Immunosuppressive treatment should be included in the first line treatment of patients with RPF and should be maintained long term. Imaging studies are better than CRP measurements in the evaluation of response to treatment.

Adult↗

[Classification and diagnosis of immunodeficiency syndromes].

Primary immunodeficiency diseases of the adult are rare disorders, but often lead to serious consequences. Therefore an early diagnosis is critical. The variety in the clinical presentation, the complexity of the immune system and the ongoing discovery of new defects render it a difficult area for the involved physician. Due to the often imprecise complaint of a weak immune system the primary task is the identification of patients with true immunodeficiency. Subsequently, the immune defect needs to be identified in collaboration with a center for immunodeficiency disorders. The diagnostic procedure is dependent on the pattern of infections and follows a defined series of steps. This procedure should prevent costly diagnostic evaluation when not indicated, and also prevent the delayed diagnosis of patients with manifest immunodeficiency disease.

Adult↗

Reduction of soluble complement receptor 2/CD21 in systemic lupus erythomatosus and Sjogren's syndrome but not juvenile arthritis.

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The amount of sCD21 in serum may modulate immunity as sCD21 levels are correlated with several clinical conditions. We report here the serum levels of sCD21 in juvenile arthritis (JA), systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). Using enzyme-linked immunosorbent assay, we determined sCD21 levels in SLE, SS and JA patients. Mann-Whitney test for nonparametric two-tail P value was performed to obtain statistical significance. Cytometrical analysis of synovial fluid leucocytes of JA patients was done on a FACSsort. While sCD21 levels in SLE and SS are reduced to levels previously found in rheumatoid arthritis (RA), JA sCD21 levels were normal. sCD21 levels did not correlate with clinical parameters and immunophenotype of synovial cells. CD4 T cells in the synovium were almost all of the CD45RO memory type and 13 of 40 patients displayed synovial expansion of gammadeltaT cells. CD21 shedding in JA differs from RA/SS/SLE. JA sCD21 levels in synovial fluid are always lower compared to blood levels of the same patients. Analysis of JA synovial T cells indicates a T-cell driven response.

Arthritis, Juvenile↗

Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii.

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5-10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.

Acute Disease↗

Linkage of autosomal dominant common variable immunodeficiency to chromosome 5p and evidence for locus heterogeneity.

Common variable immunodeficiency (CVID, OMIM 240500) and selective immunoglobulin A deficiency (IgAD) are the most frequent primary immunodeficiencies in humans. Of the cases with CVID/IgAD, 20%-25% are familial, but the only previous claims of linkage or association are to the HLA region on chromosome 6p. We report the results of a genome-wide scan in three multiplex families with CVID, IgAD, and dysgammaglobulinemia, where affection is inherited in an autosomal dominant pattern. Two of the families are consistent with linkage to the telomeric region of chromosome 5p, whereas the third is consistent with linkage to the HLA region. Using a locus heterogeneity model and a conservative penetrance model, we obtained a LOD score of 3.35 for the 5p region. We sequenced the exons of one promising candidate gene within this region (PDCD6, also known as ALG-2) but found no causative mutation.

Adolescent↗

Infectious CNS disease as a differential diagnosis in systemic rheumatic diseases: three case reports and a review of the literature.

BACKGROUND: Immunosuppressive treatment of rheumatic diseases may be associated with several opportunistic infections of the brain. The differentiation between primary central nervous system (CNS) involvement and CNS infection may be difficult, leading to delayed diagnosis. OBJECTIVE: To differentiate between CNS involvement and CNS infection in systemic rheumatic diseases. METHODS AND RESULTS: Three patients with either longstanding or suspected systemic rheumatic diseases (systemic lupus erythematodes, Wegener's granulomatosis, and cerebral vasculitis) who presented with various neuropsychiatric symptoms are described. All three patients were pretreated with different immunosuppressive drugs (leflunomide, methotrexate, cyclophosphamide) in combination with corticosteroids. Magnetic resonance imaging of the brain was suggestive of infectious disease, which was confirmed by cerebrospinal fluid analysis or stereotactic brain biopsy (progressive multifocal leucoencephalopathy (PML) in two and nocardiosis in one patient). DISCUSSION: More than 20 cases of PML or cerebral nocardiosis in patients receiving corticosteroids and cytotoxic drugs for rheumatic disease have been reported. The clinical aspects of opportunistic CNS infections and the role of brain imaging, cerebrospinal fluid analysis and stereotactic brain biopsy in the differential diagnosis are reviewed.

Adult↗

Impaired up-regulation of CD70 and CD86 in naive (CD27-) B cells from patients with common variable immunodeficiency (CVID).

CVID is characterized by reduced serum levels of all switched immunoglobulin isotypes (IgG, IgA, IgE) predisposing patients to recurrent infections of their respiratory and gastrointestinal tract. Correspondingly, most CVID patients exhibit a severely decreased proportion of class switched memory B cells (CD19+CD27+IgD-IgM-IgG+ or IgA+) in their peripheral blood (CVID type I). We previously identified a subgroup of CVID patients showing a significantly reduced expression of CD86 and CD137 following activation in vitro of PBMC or purified B cells (CD19+) with anti-IgM plus IL-2. Here we extend our previous studies by asking whether highly purified, cell-sorted naive B cells show already an expression defect of B cell surface molecules relevant in activation (CD39, CD69), differentiation (CD24, CD27, CD38) or T-B interaction (CD25, CD70, CD86). We stimulated cell-sorted, naive B cells (CD19+CD27-IgM+IgDhighIgG-IgA-) from 10 CVID patients and 10 healthy controls for 4 days with anti-IgM plus IL-2 in the absence or presence of autologous CD4+ T cells and measured the expression of the referred surface molecules. Based on reduced or normal numbers of switched memory B cells the CVID patients had previously been classified into eight type I patients and two type II patients, respectively. Interestingly, only the molecules CD25, CD70 and CD86, all relevant in cognate T-B interaction, showed a significantly lower expression in naive B cells from CVID patients compared to controls. While coculture with autologous CD4+ T cells normalized the CD25 expression, CD70 and CD86 expression remained subnormal, notably in the eight CVID patients of type I. These findings strongly suggest an intrinsic signalling or expression defect for CD70/CD86 at the level of naive B cells in type I CVID patients.

Adult↗

Successful IL-2 therapy for relapsing herpes zoster infection in a patient with idiopathic CD4+ T lymphocytopenia.

Idiopathic CD4+ T lymphocytopenia (ICL) has been defined by the center of disease control as a rare cause of immunodeficiency with a variable clinical course and an unknown aetiology. Here we describe a 65-year old patient with relapsing generalized herpes zoster infection due to ICL and a severe panlymphocytopenia. In vitro assays revealed an enhanced activation of CD8+ T cells and an increased sensitivity of activated CD4+ T cells for cell death. The clinical outcome was substantially improved after starting the patient on a subcutaneous therapy with IL-2.

Adult↗

Efficient generation of transgenic BALB/c mice using BALB/c embryonic stem cells.

BALB/c is one of the most widely used and best characterized mouse strains in immunology. For various applications, it is necessary to generate BALB/c transgenic mice. However, using the conventional microinjection technique it is extremely inefficient to produce transgenic BALB/c mice since the one-cell stage BALB/c embryos are highly vulnerable to pronuclear DNA microinjection. To overcome this problem, we have investigated the generation of Egr-1 (early growth response gene) transgenic mice via the transfection of BALB/c embryonic stem cells. Transfectants carrying Egr-1 constructs comprising either the immunoglobulin heavy chain or the MHC class II promoter/enhancer system were injected into C57BL/6 host blastocysts resulting in chimeric mice. For both type of expression vectors, transgenic offspring of the germline chimeras expressed recombinant Egr-1 in lymphoid tissues containing B cells. This demonstrates the successful generation of Egr-1 transgenic BALB/c mice using transfected ES cell.

Animals↗

Rheumatoid factor B cell tolerance via autonomous Fas/FasL-independent apoptosis.

Normal individuals do not express the high-affinity autoantibodies specific for self-IgG (rheumatoid factors, RF) that are commonly seen in rheumatoid arthritis patients. Studies of transgenic mice expressing a human IgM rheumatoid factor have shown that one mechanism by which higher affinity RF B cells are tolerized to IgG is through abortive RF B cell activation followed by deletion in the absence of T cell help. We show that RF B cell deletion occurs through an intrinsic apoptotic mechanism that is independent of the Fas/FasL pathway and does not involve active killing by T cells, as it occurs in RAG-1-deficient RF transgenic mice to the same extent as in the parental RF transgenic line.

Animals↗