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P Lamprecht

Publications and source records attributed to P Lamprecht.

At least 19 recordsLinked to original sources
PubMed2007

[Report on the 34th meeting of the German Clinical Immunology Workgroup, Frankfurt, 03.-04.11.2006].

The annual meeting of the Clinical Immunology Workgroup focused on autoimmune vasculitides. The role of innate immunity, T- and B-cells, and innovative therapies for autoimmune vasculitides was discussed. Further topics of the meeting were the role of endothelial microparticles, ghrelin and leptin, regulatory and effector-memory T-cells in ANCA-associated vasculitides, as well as the lethal midline granuloma, intracytoplasmic cytokine-profile in Behcet's disease, autoantibodies in rheumatoid arthritis, polyarteritis nodosa with cranial manifestation, ILT6 as genetic marker in multiple sclerosis and Sjögren's syndrome, alpha-fodrin autoantibodies in multiple sclerosis, interferon-g autoantibodies in a patient with atypical mycobacteriosis, and autoreactive T-cells in murine lupus.

Allergy and Immunology↗
PubMed2005

B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions.

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) are highly specific for Wegener's granulomatosis (WG). Evidence for a pivotal role of PR3-ANCA in the induction of vasculitis has been demonstrated. B cell clusters have been observed within endonasal biopsy specimens. OBJECTIVES: To determine whether B cell selection and maturation take place in granulomatous lesions of WG. METHODS: Granulomatous lesions and the immunoglobulin (VH) gene repertoire from nasal tissue of six WG patients-two active and two smouldering localised WG (ANCA negative, restricted to respiratory tract), plus one active and one smouldering PR3-ANCA positive generalised WG-were characterised by immunohistochemistry, polymerase chain reaction, cloning, DNA sequencing and database comparison. RESULTS: B lymphocyte-rich, follicle-like areas were observed proximal to PR3 positive cells and plasma cells in granulomatous lesions; 184 VH genes from these granulomatous lesions were compared with 84 VH genes from peripheral blood of a healthy donor. The mutational pattern of VH genes from active WG resembled memory B cells. Structural homologies of VH genes from granulomatous lesions to PR3-ANCA encoding genes were detected. Significantly more genes (55%, 45%, and 53%, respectively) from active WG compared with the healthy repertoire carried mutations to negatively charged amino acids within the binding site coding regions, favouring affinity to the positively charged PR3. CONCLUSIONS: Selection and affinity maturation of potentially PR3-ANCA producing autoreactive B cells may start in granulomatous lesions, thereby contributing to disease progression from ANCA negative localised to PR3-ANCA positive generalised WG.

Aged↗
PubMed2005

Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations.

OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) in patients with refractory Wegener's granulomatosis (WG). PATIENTS AND METHODS: Eight consecutive patients with active refractory WG were included. In all patients disease activity had persisted despite standard treatment with cyclophosphamide and prednisolone, as well as tumour necrosis factor alpha blockade 3 months before inclusion in the study. Patients had particular granulomatous manifestations like retro-orbital granulomata (n=5), nodules of the lungs (n=1), and subglottic stenosis (n=2). RTX was given intravenously every 4th week in combination with the standard treatment in five patients and with methotrexate in two others. Disease extent and activity were monitored clinically by interdisciplinary care, immunodiagnostics (ANCA serology, B cells by flow cytometry), and magnetic resonance imaging. RESULTS: Beneficial response and a reduction in disease activity were seen in three patients, two of whom went into complete remission. In three other patients, disease activity remained unchanged while the disease progressed in the remaining two patients. In all patients peripheral blood B cells fell to zero during treatment with RTX. cANCA titres remained unchanged in all except one patient. CONCLUSION: In this pilot study, B lymphocyte depletion was not associated with a change of the ANCA titres or obvious clinical improvement of refractory granulomatous disease in patients with WG. Further studies are needed to evaluate the role of RTX in WG.

Adult↗
PubMed2005

[Jaccoud arthritis in systemic lupus erythematosus].

Jaccoud arthritis is a manifestation of systemic lupus erythematosus and other rheumatic diseases. It is characterized by non-erosive subluxation and synovialitis ultimately leading to severe deformity of the hands. The clinical aspect may be misleading and suggestive of rheumatoid arthritis manifestations.

Adult↗
PubMed2005

[Early diagnosis of vasculitides].

The often unspecific symptoms like myalgias, fever and weight loss at the onset of vasculitides are a frequent cause for a delay in diagnosis. Organ-specific symptoms like hemoptysis, dyspnoea, epistaxis, edema and organ infarcts a present when organ dysfunction occurs as a result of vasculitis. Targeted serologic testing including antineutrophil cytoplasm antibodies (ANCA) and cryoglobulins allows early diagnosis of certain vasculitides. Modern imaging techniques like magnetic resonance imaging, computed tomography, positron-emission tomography and ultrasound are cornerstones for an early diagnosis as they allow the detection of subclinical disease and are helpful in the identification of a site for biopsy. Bioptic proof of vasculitis is still the gold standard for diagnosis. Functionally relevant damage caused by systemic inflammatory disorders can by reduced or sometimes avoided by early initiation of treatment. This requires a correct diagnosis is made as early as possible.

Diagnosis, Differential↗
PubMed2005

Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides.

There is substantial evidence that T-cells are off balance in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Genetic risk factors may influence shaping of the TCR repertoire and regulatory control of T-cells in predisposed individuals. T-cells are found in inflammatory lesions. Vigorous Th1-type responses are seen in Wegener's granulomatosis and microscopic angiitis, whereas a Th2-type response predominates in Churg-Strauss syndrome. Oligoclonality and shortened telomers indicate antigen-driven clonal expansion and replicative senescence of T-cells in ANCA-associated vasculitides. Potent CD28(-) Th1-type cells displaying an effector-memory/late differentiated, senescent phenotype are expanded in peripheral blood and are found in granulomatous lesions in Wegener's granulomatosis. Differences in proliferative peripheral blood T-cell responses to the autoantigens proteinase 3 (PR3)- and myeloperoxidase (MPO) have not consistently been detected between patients with ANCA-associated vasculitides and healthy controls in vitro. To recognize an autoantigen, break tolerance, and maintain autoimmune disease T- and B-cells require particular triggers and lymphoid structures. There is preliminary evidence of lymphoid-like structures and possible maturation of autoreactive PR3-ANCA-specific B-cells in granulomatous lesions in Wegener's granulomatosis. Alteration of the T-cell response and anomalous autoantigen-presentation in lymphoid-structures could facilitate development of autoimmune disease in ANCA-associated vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Is PR3-ANCA formation initiated in Wegener's granulomatosis lesions? Granulomas as potential lymphoid tissue maintaining autoantibody production.

In Wegener's granulomatosis (WG), antiproteinase 3 (PR3) autoantibodies (PR3-ANCA) are crucial in the development of generalized vasculitis. Wegener's pathognomonic lesion, a granulomatous inflammation of the upper and lower respiratory tract, contains abundant lymphocytes and macrophages. Lymphocyte clusters in germinal center-like formation within the granulomatous lesion are frequently observed, which suggests antigen-driven B cell maturation. Wegener's autoantigen PR3, the target for autoreactive B and T cells, is expressed in granulomatous lesions. Disease progression in WG is accompanied by a profound generalized alteration of T cell differentiation with an increase of effector memory T cells (CD4(+)CD28(-)). The cytokine profile suggests an aberrant Th1-type response either to an environmental trigger and/or the autoantigen PR3 itself. Staphylococcus aureus, a risk factor for disease exacerbation, is widely present in the upper airways in WG. The Ig gene repertoire from WG lesions indicates a predominance of VH3+ B cells with affinity to PR3 as well as to the S. aureus B cell superantigen SPA. Hence, within the WG lesion, S. aureus might support the maturation of PR3-affinity B cells that enter a germinal center reaction in contact with PR3 and T cells and expand, leading to PR3-ANCA production. Thus, granulomatous lesions could represent a potential lymphoid tissue-maintaining autoantibody production rather than a simple, random leukocyte accumulation in WG.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2004

[Trypanosomiasis in a woman from Cameroon mimicking systemic lupus erythematosus].

HISTORY: A 27-year-old woman from Cameroon was admitted because of arthralgia, myalgia and severe thrombocytopenia (20,000/ micro l). She had been suffering from weakness, recurrent febrile episodes, generalized lymphadenopathy and pancytopenia for 2 years. Having a typical autoantibody constellation and fulfilling four (pleurisy, autoimmune-hemolytic anemia, antinuclear antibodies (ANA), anti-Sm antibodies) of the American College of Rheumatology (ACR) classification criteria, systemic lupus erythematosus (SLE) had been diagnosed at another hospital. Treatment with corticosteroids and azathioprine did not improve her condition. INVESTIGATIONS: Abnormal laboratory findings were pancytopenia, elevated markers of inflammation and extreme hypergammaglobulinemia (70 %) with polyclonal IgM (73 g/l). Antinuclear antibodies (ANA), anti-Sm-, anti-Scl 70-, anti-U1-RNP-, anti-histo-, anti-leukocyte- and IgM anticardiolipin antibodies were detected. A bone marrow biopsy showed polyclonal B-cell and plasma cell infiltrates. Examination of peripheral blood smears disclosed trypanosoma brucei infection. DIAGNOSIS, TREATMENT AND COURSE: After the diagnosis of stage 2 West African trypanosomiasis (sleeping sickness) specific treatment was initiated leading to subsequent remission of the disease. CONCLUSION: This case report underlines the importance of a thorough differential diagnosis in cases of suspected autoimmune disease. Induction of autoantibodies during infectious diseases may be misleading. The use of the ACR criteria for SLE must be restricted to the classification of proven connective tissue diseases.

Adult↗
PubMed2004

Maintenance of remission with leflunomide in Wegener's granulomatosis.

OBJECTIVE: To investigate the safety and efficacy of leflunomide plus low-dose prednisolone for the maintenance of remission in Wegener's granulomatosis (WG). METHODS: This was a Phase II, single-centre, open-label clinical investigation of patients with generalized WG treated with leflunomide after the induction of complete (n = 4) or partial (n = 16) remission by cyclophosphamide/prednisolone combination therapy. Leflunomide treatment was initiated at 20 mg/day and increased to 30 mg/day after 12 weeks and, in patients with partial remission, to 40 mg/day after 24 weeks. Concomitant low-dose prednisolone (< or =10 mg/day) was allowed during the study. In addition to the frequency of relapse, treatment efficacy was assessed by the standard measures of disease activity/extent. RESULTS: A total of 20 patients were enrolled in the trial. During a treatment period of up to 2.5 yr (median 1.75 yr, range 1-2.5 yr), one patient had a major relapse and required retreatment with cyclophosphamide/prednisolone. Eight patients had minor relapses that were successfully treated by dose increases to 40 mg/day leflunomide. Disease activity remained unchanged for the duration of the study. The most frequently reported adverse events were mild respiratory infection (40%), arthralgia (35%) and hypertension (35%); dry skin, nail disorder and diarrhoea were each reported by 30% of patients. Despite the aggressive pretreatment with cyclophosphamide, adverse events with leflunomide treatment at the higher dose (30-40 mg/day) were comparable with those seen with the standard dose (20 mg/day) for rheumatoid arthritis patients. CONCLUSION: Leflunomide appears to be safe and well tolerated for the maintenance of complete or partial remission of WG. The results of this pilot study encourage further controlled trials comparing leflunomide with alternative remission maintenance therapies.

Adult↗
PubMed2004

[Hereditary periodic fever].

Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D periodic fever syndrome (HIDS), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are hereditary periodic fever syndromes. FMF is caused by mutations in the Mediterranean fever gene, HIDS by mutations in the mevalonat-kinase gene, and TRAPS by mutations in the TNF-receptor superfamily 1A gene. Impaired function of the encoded proteins, i.e. pyrin in FMF, mevalonat-kinase in HIDS, and the p55 TNF-receptor in TRAPS, induces a dysregulated cytokine balance. Clinical manifestations are relapsing fever, serositis, arthralgia, myalgia, and miscellaneous forms of rash. The diagnosis is made through moleculargenetic analysis of mutations of the MEFV-gene (FMF), MVK-gene (HIDS), or TNFRSF1A-gene (TRAPS). Colchicine is the therapy of choice in FMF. HIDS is treated symptomatically. Impaired TNF-alpha regulation in TRAPS can be treated with etanercept.

Cytokines↗