Relationship between urinary sialylated saccharides, serum amyloid A protein, and C-reactive protein in rheumatoid arthritis and systemic lupus erythematosus.

The urinary excretion of sialic-acid-containing oligosaccharides, total sialic acid, serum amyloid A protein (SAA), and C-reactive protein (CRP) has been studied in 48 patients with rheumatoid arthritis (RA) and in 17 patients with systemic lupus erythematosus (SLE). Linear regression analysis revealed a close positive correlation between serum SAA and CRP levels in both RA (r = 0.71, p less than 0.001) and SLE (r = 0.86, p less than 0.001). The urinary excretion of sialyl lactose showed a positive correlation with the serum levels of SAA and CRP in RA (r = 0.45 and r = 0.45, respectively, p less than 0.01) but not in SLE (r = 0.05 and r = 0.10 respectively). Changes in serum total sialic acid levels paralleled those in CRP and SAA in RA as well as in SLE. Patients with very active RA had higher urinary sialyl oligosaccharide excretion (p less than 0.001), higher CRP levels (p less than 0.01), and higher SAA levels ( p less than 0.05) than those with moderately active disease.     

Circulating DNA-antibodies in systemic lupus erythematosus

Summary Sera from 57 patients with systemic lupus erythematosus (SLE) were tested for DNA-antibodies by three different methods: a radioimmunological test using the Farr technique, the Crithidia luciliae immunofluorescence assay for anti-double-stranded (native) DNA (anti-ds-DNA), and a solid-phase immunoenzymatic assay for anti-single-stranded (denatured) DNA (anti-ss-DNA) of IgG and IgM classes. There was a positive correlation between the activity of the disease and the levels of ds-DNA-antibodies and IgG anti-ss-DNA. Patients with active nephritis had a higher amount of anti-ds-DNA and anti-ss-DNA of IgG class than patients with inactive nephritis (P<0.05 and 0.01, respectively). Patients with SLE nephritis had lower levels of ss-DNA-antibodies of IgM class than patients without nephritis (P<0.02). There was a positive correlation between the IgG-anti-ss-DNA/IgM-anti-ss-DNA ratio and the activity score of the disease. These results suggest that the anti-ss-DNA assay may be useful in the follow-up of SLE. Complement fixing anti-ds-DNA and the highest levels of anti-ds-DNA by Farr assay were usually associated with an active disease, especially nephritis and joint involvement.     

Coronary Flow Reserve Is Impaired in Young Men With Familial Hypercholesterolemia

Objectives. We sought to investigate whether functional abnormalities in coronary vasomotion exist in young adults by studying 15 men (age 31 ± 8 years [mean ± SD]) with familial hypercholesterolemia (FH) and a matched group of 20 healthy control subjects.

Background. Precursors of morphologic coronary artery disease are known to be present in adolescents and young adults with a high risk factor profile.

Methods. Myocardial blood flow was measured at the basal state and during dipyridamole-induced hyperemia using positron emission tomography and oxygen-15–labeled water.

Results. Serum total and low density lipoprotein cholesterol concentrations were higher in the patients than in the control subjects (mean ± SD): 7.7 ± 1.9 versus 5.3 ± 1.5 mmol/liter (298 ± 73 vs. 205 ± 58 mg/dl) and 6.1 ± 1.8 versus 3.5 ± 1.4 mmol/liter (236 ± 70 vs. 135 ± 54 mg/dl), respectively (both p < 0.001). The baseline myocardial blood flow was similar in the patients and control subjects: 0.92 ± 0.24 versus 0.83 ± 0.13 ml/g per min, respectively (p = 0.21). A significant increase in flow was observed in both groups after dipyridamole infusion, but the flow at maximal vasodilation was 29% lower in the patients: 3.19 ± 1.59 versus 4.49 ± 1.27 ml/g per min (p = 0.011). Consequently, coronary flow reserve (the ratio of hyperemia flow to basal flow) was 35% lower in the patients than in the control subjects: 3.5 ± 1.6 versus 5.4 ± 1.5 (p = 0.0008). Total coronary resistance during hyperemia was higher in the patients than in the control subjects: 36 ± 25 versus 21 ± 10 mm Hg/min per g per ml (p = 0.045). Coronary flow reserve was inversely associated with serum total cholesterol concentration: r = −0.43 (p = 0.009).

Conclusions. Coronary flow reserve is reduced in young men with FH, and, consequently, coronary resistance during hyperemia is increased. The results demonstrate very early impairment of coronary vasomotion in hypercholesterolemic patients.

(J Am Coll Cardiol 1996;28:1705–11)     

Urinary excretion of sialic acid-containing saccharides in systemic lupus erythematosus

Urinary sialic acid-containing trisaccharides, total sialic acid, and serum sialic acid were studied in 17 patients with systemic lupus erythematosus (SLE) and in 15 healthy controls. The urinary excretion of sialyllactose, measured by a gas chromatographic method, was significantly greater in patients with SLE (37.4 ± 21.4 mg/24 hours, SD) than in the control subjects (13.7 ± 3.8 mg/24 hours, P < 0.001). The mean excretion of sialyl-N-acctyllactosamine (16.6 ± 8.5 mg/24 hours) and total sialic acid (82.5 ± 29.4 mg/24 hours) was also greater in the SLE group than in the controls (8.7 ± 2.8 and 58.0 ± 16.0 mg/24 hours, respectively; P < 0.01). Serum levels of sialic acid were correspondingly higher in the SLE patients (84.4 ± 20.4 mg/100 ml) than in the controls (63.7 ± 6.5 mg/100 ml, P < 0.001). Urinary excretion of sialyl-lactose correlated positively with clinical disease activity (P < 0.001) and with anti-DNA antibody levels (P < 0.05). On the average, patients with moderate or severe disease excreted three times more sialyl-lactose than did those with mild or inactive disease. Our results suggest that the excretion of sialyl-oligosaccharides reflects disease activity in SLE.     

Clinical value of serum amyloid A and C-reactive protein measurements in secondary amyloidosis

Serum amyloid A protein (SAA) and C-reactive protein (CRP) are acute-phase reactants synthesized by the liver. A close relationship was found between SAA and CRP concentrations in various rheumatic diseases (rs = 0.74 to 0.83). The serum concentration of these proteins reflected the activity of the rheumatic inflammation in a sensitive way. In secondary amyloidosis, persistently high SAA and CRP levels correlated closely with the progression of the renal amyloid manifestations. The findings show that measurements of SAA and CRP concentrations are valuable in assessing disease activity and the effect of therapy in rheumatic diseases, as well as in the assessment of the prognosis in secondary amyloidosis. Therapeutic measures that decrease SAA levels may reduce amyloid formation.     

Change in Cellular Phenotype from Lymphoid to Erythroid in a Case of ALL

Acute leukaemia was diagnosed in a 3-month-old boy. Initial blood leucocyte count was 97 × 10⁹/1, 92% of the cells were morphologically small lymphoblasts which according to surface marker analysis were of the common ALL (non-T non-B) type. Remission was achieved with initial treatment. During relapse 5 months later a morphologically different leukaemic cell appeared in the bone marrow, blood and liquor. This cell type which dominated during the terminal stage of the disease was larger and had an abundant bosophilic cytoplasm which contained PAS-positive granulae. Sudan, myeloperoxidase and benzidine staining gave negative results. Neither T nor B lymphocyte markers were seen but a strong surface expression of glycophorin A was found by indirect immunofluorescence with specific rabbit anti-glycophorin A antiserum. The cells showed a unique surface glycoprotein pattern. Bone marrow karyotype analysis gave in about 80%: 47,XY, + 8,t(4:11) indicating that this blast cell represented a malignant clone. As glycophorin A is expressed exclusively on erythroid cells and their precursors, this finding indicates a change from a ‘lymphoid’ to an erythroid phenotype of the leukaemic cells during the course of the disease.