Meningeal involvement in Wegener's granulomatosis confirmed and monitored by positive circulating antineutrophil cytoplasm in cerebrospinal fluid.

MRI and CSF investigations revealed meningeal involvement in a 29-year-old patient with biopsy-confirmed Wegener's granulomatosis. The intracranial manifestation of Wegener's granulomatosis was supported by the detection of pathologic circulating antineutrophil cytoplasm (c-ANCA) in the CSF. We monitored disease activity by c-ANCA measurement in the CSF. After repeated cycles of intrathecal administration of methotrexate and corticoids, progression of meningeal infiltration stopped, and CSF c-ANCA titers became negative.

125I-Angiotensin II binding to human blood cells.

The binding of 125I-angiotensin II to human blood cells was investigated. Blood was drawn from healthy volunteers and platelets prepared with minimal contamination of red cells and white blood cells (less than 0.1%). Using thin layer chromatography, degradation of 125I-angiotensin II by platelets could be demonstrated in the presence of various enzyme inhibitors. However, when incubated with 1 mM diisopropylfluorophosphate (DFP) or 1 mg/ml bacitracin, no breakdown of 125I-angiotensin II could be detected. The amount of specifically bound 125I-angiotensin II increased linearly with the number of cells per tube. Binding reached a plateau within 90-120 min at 37 degrees C, and was stable thereafter. Specific binding was reversible. No binding could be detected at 4 degrees C. Specific binding of 125I-angiotensin II was saturable. Scatchard analysis of binding by platelets of healthy volunteers revealed one class of binding sites with an apparent Kd of 127 +/- 16 pM and a maximal binding capacity of 7.9 +/- 1.5 binding sites per cell. Competitive displacement of 125I-angiotensin II binding by angiotensin II-analogues showed a rank order of effectiveness. Unrelated peptides, e.g. bradykinin, vasopressin and enkephalin, did not displace specifically bound angiotensin II. Human mononuclear leucocytes were prepared by a Ficoll-isopaque gradient. However, these cells could not be used for studies of specific binding, since enzymatic degradation of 125I-angiotensin II could not be prevented despite addition of various enzyme inhibitors. Time-dependent uptake of 125I-angiotensin II showed no stable plateau. Thus our study shows specific binding of 125I-angiotensin II to human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level.

The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.

Anti-chromatin and anti-C1q antibodies in systemic lupus erythematosus compared to other systemic autoimmune diseases.

OBJECTIVE: To evaluate the prevalence, sensitivity, and specificity of anti-chromatin and anti-C1q antibodies in systemic lupus erythematosus (SLE) and lupus nephritis compared to small vessel vasculitis and other connective tissue diseases. To provide long-term follow-up data for anti-chromatin antibodies in lupus nephritis. METHODS: We determined the significance of anti-nuclear antibodies (ANA), anti- double-stranded DNA (anti-dsDNA), anti-chromatin, and anti-C1q antibodies, as well as complement factors C3 and C4, in relation to disease activity in SLE patients with (n = 47; long-term follow-up data for 33 patients) and without (n = 31) biopsy-confirmed lupus nephritis, microscopic polyangiitis (n = 37), Wegener's granulomatosis (n = 66), primary Sjögren's syndrome (n = 17), limited scleroderma (CREST syndrome) (n = 6), and progressive systemic scleroderma (PSS) (n = 11). RESULTS: Anti-chromatin antibodies were more specific and sensitive than anti-C1q antibodies in distinguishing SLE patients from those with other systemic autoimmune diseases [anti-chromatin: sensitivity 64.1%, specificity 99.2%, odds ratio (OR) 219.6; anti-C1q: sensitivity 50%, specificity 72.6%, OR 2.65]. Anti-C1q antibodies were present in 75% of patients with Sjögren's syndrome and 35.1% of patients with microscopic polyangiitis. Anti-chromatin antibodies could identify SLE in patients with positive ANA but negative anti-dsDNA antibodies. Persisting anti-chromatin antibodies indicated SLE disease activity, even if anti-dsDNA antibodies had become negative. In long-term follow-up, those SLE patients with negative anti-dsDNA antibodies but persisting ANA and anti-chromatin antibodies relapsed if immunosuppression had been tapered. Anti-chromatin antibodies correlated with the SLE disease activity index (SLEDAI) as a marker of disease activity. CONCLUSIONS: The measurement of anti-chromatin, but not anti-C1q, antibodies in patients with systemic autoimmune diseases increases diagnostic sensitivity and specificity for SLE and assists in treatment decisions in anti-dsDNA-negative patients.

CRP levels in autoimmune disease can be specified by measurement of procalcitonin.

Autoimmune diseases (AID) are prone to infection particularly under immunosuppression. The differentiation of infection from active AID is often difficult. In order to specify the diagnostic value of measurement of procalcitonin (PCT) in AID 81 patients with anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis were analyzed, 27 with rheumatoid arthritis and 25 patients with systemic lupus erythematosus at various stages of the disease. Although PCT levels (95th percentile) were below 0.5 ng/ml in patients with active systemic lupus erythematosus and rheumatoid arthritis, the cutoff for normal values (95th percentile) in patients with active ANCA-positive vasculitis was 0.89. Therefore PCT levels of < 1 ng/ml are recommended as cutoff for invasive infections in patients with ANCA-positive vasculitis. In view of the increased mortality under immunosuppression in patients with AID and additional bacterial infection the measurement of PCT is helpful when an infectious origin is suspected.

Specific binding of angiotensin II and atrial natriuretic factor in non-nephropathic type I diabetes mellitus.

We examined ten patients with type I diabetes mellitus and ten age- and sex-matched healthy controls. Median duration of diabetes was 7 years (range 0.5-24). None of the diabetic patients had hypertension, microalbuminuria, or proliferative retinopathy. Maximal specific binding capacity for angiotensin II to thrombocytes was significantly increased in diabetics (Bmax 11.9 +/- 1.6 sites per cell vs 7.0 +/- 0.9 in controls; P less than 0.01). In contrast, maximal binding for atrial natriuretic factor tended to be lower in type I diabetics (8.84 +/- 1.25 sites per cell vs 16.8 +/- 2.97; P less than 0.07). There was no difference of apparent dissociation constant (KD) for either receptor. Angiotensin II values (RIA) were greater in diabetics (16.2 +/- 1.5 pg/ml vs 8.5 +/- 1.4 in controls; P less than 0.02) and concentrations of atrial natriuretic factor (RIA) were not significantly different. The data suggest increased angiotensin II binding despite high angiotensin II concentrations in non-nephropathic type I diabetic patients. These findings may be relevant when considering the evolution of hypertension and microangiopathy lesions.