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F Hiepe

Publications and source records attributed to F Hiepe.

At least 19 recordsLinked to original sources
PubMed1999

Autoantibodies in primary Sjögren's syndrome are directed against proteasomal subunits of the alpha and beta type.

OBJECTIVE: The proteasome subunit HC9 (alpha3) has recently been identified as a major target of the humoral autoimmune response in patients with autoimmune myositis and systemic lupus erythematosus. Since B cell hyperreactivity is a common feature of systemic autoimmune diseases, patients with primary Sjögren's syndrome (SS) and other control groups were investigated to evaluate the significance of autoantibodies against the proteasome. METHODS: Analyses of autoantibodies directed against the 20S proteasome were performed using enzyme-linked immunosorbent assay, immunoblot, and 2-dimensional electrophoresis. Forty-three patients with primary SS, 47 patients with rheumatoid arthritis including 9 with secondary SS, 19 patients with gastrointestinal tumors, and 80 healthy controls were tested for antiproteasome antibodies. RESULTS: Antiproteasome antibodies were detected in 39% of patients (17 of 43) with primary SS. In contrast, only 1 of 47 patients with rheumatoid arthritis showed positive reactivity (P < 0.001). Serum samples from 19 tumor patients (P < 0.003) and 80 healthy controls (P < 0.001) were serologically negative. Moreover, immunoblotting and 2-dimensional analysis of the antiproteasome response revealed a polyspecific recognition pattern in 7 patients with primary SS. Different proteasomal subunits of the alpha and beta type, including subunits that carried the proteolytic active sites, were recognized by the patients' sera. CONCLUSION: The humoral antiproteasome response in primary SS, in contrast to its secondary form, is characterized by an extensive recognition pattern of several subunits, indicating a polyspecific B cell activation against the 20S proteasome. Moreover, proteolytically active beta-type subunits, which are important for the generation of major histocompatibility complex class I-restricted antigens, appear to be targets of the autoimmune response. The data indicate that the proteasome itself may stand on a cross point of pathways that links mechanisms of the immune defense with features of systemic autoimmunity.

Antibodies, Antinuclear↗
PubMed1999

Anti-phospholipid antibodies and CD5+ B cells in HIV infection.

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.

Adolescent↗
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↗