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F Hiepe

Publications and source records attributed to F Hiepe.

At least 19 recordsLinked to original sources
PubMed1998

Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome.

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.

Antigens↗
PubMed1998

A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus.

The SmD1 protein is a specific target for the autoantibody response in SLE. To further analyze this reactivity epitope, mapping was performed with cellulose-bound 13-mer peptides overlapping 10 amino acids (aa). In this initial approach, 4 out of 15 SLE sera recognized more than five overlapping peptides of the SmD1 C-terminus. Therefore, longer oligopeptides of up to 37 aa of this region were generated and probed for as antigens by ELISA. For the SmD1 aa 83-119 polypeptide, there was a striking increase of reactivity with 70.0% positive reactions out of 167 SLE sera. In contrast, 105 healthy control sera were negative, and only 8.3% of sera from patients with other inflammatory diseases (n = 267) exhibited a response, which was of low level only. The anti-SmD183-119 reactivity was significantly higher in anti-dsDNA antibody positive vs. negative sera (P < 0.001) and correlated with disease activity. Four of five human monoclonal anti-dsDNA antibodies also reacted with SmD183-119. The specificity for SmD1 was demonstrated by inhibition experiments and immunization of rabbits with SmD183-119 inducing SmD1-specific antibodies. In conclusion, the SmD183-119 peptide was demonstrated to be an important and highly specific target of the autoimmune response in SLE. The high sensitivity of this ELISA probably depends on a conformational epitope, which appears not to be accessible in the full-size SmD1 protein.

Amino Acid Sequence↗
PubMed1998

[Iloprost administration over 21 days as an effective therapy in systemic scleroderma--case report and review of the literature].

A 57-years old female patient with systemic sclerosis underwent a prolonged intravenous therapy during 21 consecutive days with iloprost, a stable analogue of prostacyclin. Beginning with 0.5 ng/ kg/minute the dose was increased every 2 days up to 2 ng/kg/minute. At the end of follow up, Iloprost was shown to enhance the perfusion of the finger and to improve pulmonary-function tests including the diffusion-capacity. Furthermore, the Erythrocyte Sedimentation Rate and the C-reactive protein decreased. The case report shows the necessity of a controlled study of prolonged iloprost therapy.

Clinical Trials as Topic↗
PubMed1997

Value of anticardiolipin antibodies for monitoring disease activity in systemic lupus erythematosus and other rheumatic diseases.

The prevalence of anticardiolipin antibodies in active systemic lupus erythematosus (SLE) was compared with that in inactive SLE and other rheumatic and non-rheumatic diseases to determine the value of these autoantibodies in monitoring rheumatic diseases. Pairs of IgG- and IgM-aCL were measured by ELISA in 173 consecutive hospitalised patients, including 141 with rheumatic diseases (18 active SLE, 21 inactive SLE, 19 rheumatoid arthritis, 13 reactive arthritis, 7 other spondyloarthropathies, 16 vasculitis, 47 other autoimmune diseases) and 32 non-rheumatic controls. A further 101 aCL pairs were determined during follow-up in 19 patients with SLE. Serum concentrations were analysed with respect to SLE activity and compared between the different patient groups. IgG- and IgM-aCL levels in excess of 10 GPL and 9 MPL respectively were considered positive. 30.6% of all patients (53/173) were found to be positive for IgG-aCL, as against only 9.8% (17/173) for IgM-aCL. IgG-aCL serum levels in active SLE differed significantly from all other groups, including inactive SLE (all p < 0.005). Median IgM-aCL levels were below the cut off point in all groups, although measurable values were obtained almost exclusively in active SLE and RA. In this study IgM-aCL measurement was of less value in monitoring rheumatic diseases. IgG-aCL positivity in SLE was associated with a significantly higher odds ratio (OR) for active disease (OR 16.0, 95% confidence interval: 2.8-90.0). The results show that disease activity in SLE was accompanied by significantly increased IgG-aCL, whereas no elevation was found in other diseases. This parameter may therefore be useful in monitoring SLE activity.

Adult↗
PubMed1997

[Persistent facial swelling of unclear etiology. The differential diagnostic considerations].

A 54-year-old, obese woman suffered from massive symmetrical swelling of the face, especially of the upper and lower eyelids. Initially the swelling occurred intermittently, but after 2 years it was permanent and progressive markedly limiting her visual fields. Neither laboratory findings nor imaging procedures provided any firm evidence of an underlying cardiac, renal or endocrinological disease. There was no suggestion of a storage disease. Skin biopsy showed foam cells and granulomatous inflammation, so the patient was tentatively diagnosed as having a monosymptomatic Melkersson-Rosenthal Syndrome. Eyelid surgery was performed to improve her visual fields. Treatment with clofazimine 100 mg daily was initiated. Regular follow-up visits over 7 months revealed no evidence of recurrence. The patient died a sudden cardiac death a few months later. The relatives refused an autopsy. The definite cause of her facial swelling remains unclear as we discuss the differential diagnostic possibilities.

Biopsy↗
PubMed1997

[Autoantibodies against centrosomes in a patient with limited systemic sclerosis with ulcera cruris and arteriopathy--case report and review of the literature].

A 63 year old woman developed painful, up to 15 x 7 cm large ulcers on both lower limbs and an acral necrosis on the right big toe. The patient had no symptoms of intermittent claudication, but a history of 40 package years of cigarette smoking. Angiography showed circumscript stenosis of medium-sized vessels, deformed vessel segments, and rarification and obstruction of peripheral vessels. Arterial occlusive disease was diagnosed, and percutaneous transluminal angioplasty (PTA) of the right common iliac artery and both femoral arteries performed. However, despite documented patency of these vessels clinical symptoms worsened. The consulting rheumatologist found a history of Raynaud's syndrome, acral necrosis of the fourth finger of the right hand, sclerodactylia, and microstomia. Capillaroscopy revealed megacapillaries and vessel rarification. High titers of antinuclear antibodies with specificity for centrosomes (1:10240), which have not been described in this context to date, were detected and limited systemic sclerosis of the CREST type was diagnosed. Treatment with iloprost (50 micrograms/day i.v.) and pulsed cyclophosphamide (800 mg i.v./month) resulted in almost complete healing of the crural and digital ulcers and a significant reduction of the analgetic medication.

Antibodies, Antinuclear↗
PubMed1996

Proteasome alpha-type subunit C9 is a primary target of autoantibodies in sera of patients with myositis and systemic lupus erythematosus.

Autoantibodies occur in low frequencies among patients with myositis characterizing only distinct subsets of this disease. Most of these known antibodies are directed to enzymatically active complexes. The 20S proteasome represents an essential cytoplasmatic protein complex for intracellular nonlysosomal protein degradation, and is involved in major histocompatibility complex class I restricted antigen processing. In this study we investigated whether the 20S proteasome complex is an antibody target in myositis and in other autoimmune diseases. 34 sera of poly/dermatomyositis patients were assayed for antiproteasomal antibodies using enzyme-linked immunosorbent assay, immunoblot, and two-dimensional non-equilibrium pH gradient electrophoresis (NEPHGE). Sera was from patients with systemic lupus erythematosus (SLE), mixed connective tissue disease, and rheumatoid arthritis; healthy volunteers served as controls. In 62% (21/34) of the cases sera from patients with myositis and in 58% (30/52) of the cases sera from patients with SLE reacted with the 20S proteasome. These frequencies exceeded those of sera from patients with mixed connective tissue disease, rheumatoid arthritis, and healthy controls. The alpha-type subunit C9 of the 20S proteasome was determined to be the predominant target of the autoimmune sera in myositis and SLE. Lacking other frequent autoantibodies in myositis, the antiproteasome antibodies are the most common humoral immune response so far detected in this disease entity.

Antibodies, Monoclonal↗
PubMed1996

Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial.

OBJECTIVE: To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA). METHODS: Ninety patients with RA (disease duration < or = 3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study. RESULTS: There were no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy. CONCLUSION: Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have good response to such therapy.

Administration, Oral↗
PubMed1996

Differential recognition of the 52-kd Ro(SS-A) antigen by sera from patients with primary biliary cirrhosis and primary Sjögren's syndrome.

Antibodies against the 52-kd Ro(SS-A) protein are significantly associated with the primary Sjogren's syndrome (pSS). A small proportion of patients suffering from primary biliary cirrhosis (PBC) with secondary Sjogren's syndrome (PBC/SS) who are serologically characterized by antimitochondrial type 2 antibodies also express anti-52-kd Ro(SS-A) antibodies. The primary B-cell-derived antigenic responses by autoimmune sera were analyzed in both entities using truncated recombinant proteins to examine whether different epitopes are associated with these diseases. Sera were collected from 25 patients with pSS and 9 anti-52-kd Ro(SS-A)-positive patients suffering from PBC/SS. B-cell epitope mapping was performed using different 52-kd Ro(SS-A) fusion proteins in enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Sera from patients with pSS showed the broadest reactivity against antigenic epitopes at AA 153-245 compared to the significantly limited reactivity against AA 228-245 of sera from patients with PBC. B-cell epitopes within AA 190-245 represent immunodominant epitopes recognized by pSS sera in a significantly higher degree than by PBC sera, which react predominantly with AA 228-245 (P < .0001). Anti-La(SS-B) antibodies were significantly associated with anti-52-kd Ro(SS-A) in sera from patients with pSS compared with PBC patients (P < .025). Thus, the antibody response to 52-kd Ro(SS-A) in PBC appears to be induced differently than in pSS. Although a limited immune response to 52-kd Ro(SS-A) occurs in PBC/SS patients, a more extended epitope spreading is evident in patients with pSS.

Adult↗
PubMed1996

Behet's syndrome with pulmonary involvement-combined therapy for endobronchial stenosis using neodym-YAG laser, balloon dilation and immunosuppression.

We present a case report of a patient suffering from Behet's syndrome with pulmonary involvement. The development of endobronchial granulomatosis in the bronchus intermedius and right upper lobe bronchus led to severe bronchial stenosis and dyspnoea. Also aphthous ulcerations in the bronchial mucosa occurred. Treatment of the granulomatous stenosis consisted of Neodym-YAG laser resection and immunosuppression. On follow-up there was a recurrence of the stenosis, characterised by fibrotic strictures. Therefore a balloon dilation was performed and immunosuppression instituted, which led to an increase in airway diameter and a reduction in dyspnoea. These clinical results suggest that recanalisation therapy with Neodym-YAG laser and/or balloon dilation with additional immunosuppression is suitable in benign stenosis (granulomatous or fibrotic), caused by Behet's disease.

Adult↗
PubMed1996

Diagnosis of alveolitis in interstitial lung manifestation in connective tissue diseases: importance of late inspiratory crackles, 67 gallium scan and bronchoalveolar lavage.

The diagnostic relevance of bronchoalveolar lavage (BAL) and associated non-invasive findings in connective tissue diseases (CTD) has not been established regarding alveolitis so far. The goal of the study was to determine the relations between BAL cell differential count and findings of non-invasive diagnostic procedures for alveolitis to predict the clinical value of BAL in CTD. One hundred-five patients (92 non-smokers; 13 smokers) with CTD (73 patients with systemic sclerosis, 19 with systemic lupus erythematosus, 13 with primary Sjögren's syndrome) had symptoms or signs of lung involvement and were further examined (lung function test, chest radiography, thoracic computed tomography, 67 gallium scintigraphy and BAL). The relations between BAL in middle lobe and cell count differentiation to non-invasive investigations were analyzed by logistic regression. In all CTD patients investigated a pulmonal involvement occurred based on non-invasive methods. Regarding non-invasive methods, alveolitis determined by BAL cell differential count was significantly associated with an increased 67-gallium uptake and late inspiratory crackles (P < 0.01), and to a lesser extent with an abnormal interstitial pattern in CT (P < 0.055). Parameters of lung function and laboratory parameters were related to alveolitis using multivariate testing. Considering the alveolitis subtype (granulo- or lymphocytosis), only a reduced FEV1 showed a relationship to granulocytic alveolitis (P < 0.01). Late inspiratory crackles and increased 67 gallium uptake as non-invasive diagnostic findings point out alveolitis in CTD remarkably. Therapeutic and prognostic aspects necessitate BAL to specify the type of alveolitis (lymphocytosis or granulocytosis or mixed forms) in CTD patients with lung manifestation. Non-invasive diagnostic procedures cannot predict the type of alveolitis sufficiently.

Adult↗
PubMed1996

Anti-52 kDa Ro(SSA) autoantibodies in different autoimmune diseases preferentially recognize epitopes on the central region of the antigen.

OBJECTIVE: Antibodies against the 52 kDa Ro(SSA) protein are an important laboratory variable in autoimmune diseases, most notably in the diagnosis of primary Sjogren's syndrome (SS), congenital heart block (CHB), and certain varieties of systemic lupus erythematosus (SLE). However, there is controversy about the differential reactivity of these sera, both with regard to immunogenic regions on the target protein and the respective antibody titers. Therefore, sera from various autoimmune diseases were tested against a broad panel of recombinant 52 kDa Ro(SSA) fusion proteins. METHODS: Sera were obtained from 20 patients with SLE, 10 with primary SS, 15 children with CHB, 6 healthy anti-52 kDa Ro(SSA) positive infants born to mothers with SLE and 7 anti-52 kDa Ro(SSA) positive patients with primary biliary cirrhosis/secondary SS. Epitope mapping was performed using different fusion proteins in ELISA and immunoblot. RESULTS: All sera reacted with whole recombinant antigen as well as with the protein carrying the amino acid sequence (AA) 1-245. The proportion of positive sera against the 52kDa Ro fusion proteins tested was found in descending order in patients with CHB, down to primary SS, the healthy infants group, patients with SLE and finally primary biliary cirrhosis/secondary SS. In general, CHB and primary SS sera exhibited the broadest reactivity against the recombinant protein compared to the limited and lower reactivity of sera from patients with primary biliary cirrhosis. Sera from infants with CHB had significantly higher antibody levels to AA 1-245 compared to SLE sera (p < 0.0005) and to sera from healthy infants born to SLE mothers (p < 0.05), as well as to serum samples from patients with primary biliary cirrhosis/SS (p < 0.005). The strongest antigenicities recognized by anti-52 kDa Ro(SSA) autoantibodies are located within the AA 197-245 region that represents an essential epitope. Further antigenic sites preferentially recognized by SS, CHB, and healthy infant sera are located within AA 153-196. CONCLUSION: Thus, the central region AA 153-245 is the major immunogenic region of the 52 kDa Ro(SSA) antigen containing a strong antigenic epitope between AA 197-245. The antibody response is directed to this major antigenic region regardless of the underlying autoimmune disease. However, the strikingly different quantities of antibody levels and the recognition of epitopes on AA 153-196 may be associated with different disease expressions.

Adolescent↗
PubMed1996

Production of autoantibodies against DNA and collagen after inoculation of rabbits with Trypanosoma equiperdum.

The aim of the study was to investigate the induction of autoantibodies in rabbits after the inoculation with Trypanosoma equiperdum. Eight female rabbits were inoculated s.c. with 5 x 10(6) parasites of Trypanosoma equiperdum. Four of these animals were treated with Diminazen (Berenil) at a dosage of 28 mg per rabbit by intramuscular injection 35 days p. i. Two additional non-infected rabbits served as negative controls. 9 days p.i. all infected animals possessed serum antibodies against Typanosoma equiperdum. Titers peaked to 1:2048, measured between 14 and 30 days p.i. and were persistent until the end of examinations. In parallel, there was an increase of anti-dsDNA and anti-collagen autoantibodies, but not of autoantibodies against recombinant U1RNP and La antigens. In comparison to patients with systemic lupus erythematosus, the anti-DNA binding of rabbit's sera was reduced more strongly in presence of increasing salt concentrations. In addition, the sera of inoculated rabbits recognized several unknown bands of a cell extract in immunoblotting. The parallel increase of antibodies against Trypanosoma, control foreign antigens, DNA and collagen suggests a polyclonal stimulation of the immune system. It was concluded that this rabbit model seems to be sufficient to investigate the mechanisms which are able to induce autoimmune phenomena.

Animals↗