Evaluation of paraoxonase activity in patients with mixed connective tissue disease.

OBJECTIVE: Mixed connective tissue disease (MCTD) is a systemic inflammatory autoimmune disease. The connection between inflammatory measures and atherosclerosis in MCTD has not been described. Paraoxonase (PON) is known to have an antioxidant function. We evaluated lipid profiles and PON activity in patients with MCTD. METHODS: Thirty-seven patients with MCTD were enrolled. Patients had taken no antihyperlipidemic drugs in the past 2 months. Thirty healthy individuals served as controls. The mean age of patients was 51.2 +/- 9.5 years; disease duration was 11.0 +/- 7.2 years. PON activity was determined with spectrophotometry, von Willebrand factor (vWF) antigen was investigated with the immunoturbidimetry method, and thrombomodulin and antiendothelial cell antibody (AECA) measurements were carried out by ELISA. RESULTS: PON activity in patients with MCTD was significantly lower than in the controls (patients 118.5 +/- 64.6 U/l, controls 188.0 +/- 77.6; p < 0.001). Arylesterase activity was significantly reduced in patients (p < 0.001). Reduction of PON activity showed a close correlation with the age of the patients, duration of the disease, and vascular events (eye, cardiac, cerebral). There was a close association between the low PON activity and endothelial cell activation markers (thrombomodulin, vWF, AECA). CONCLUSION: Our results indicate that in patients with MCTD there is an increased risk for atherosclerosis. In the development of atherosclerosis, besides the elevated levels of cholesterol and triglyceride, reduced PON concentrations and PON activity may play a crucial role.

Abnormal cell-specific expressions of certain protein kinase C isoenzymes in peripheral mononuclear cells of patients with systemic lupus erythematosus: effect of corticosteroid application.

We have studied the expressions of various protein kinase C (PKC) isoenzymes in T cells and monocytes from patients with systemic lupus erythematosus (SLE), in comparison to those of healthy controls and patients with other immunological disorders. As measured by Western blotting, the levels of PKCbeta, delta, eta, epsilon, theta and zeta (but not of PKCalpha) significantly decreased in T cells of SLE patients. In monocytes, however, we observed marked suppressions only in the expressions of PKCdelta, epsilon and zeta but not in the expressions of other PKC isoforms. In vivo corticosteroid application, as well as in vitro steroid treatment of monocytes, elevated the expressions of most isoforms close to normal values; however, the decreased levels of PKCtheta and zeta were not affected by steroid application. These alterations were characteristic to SLE because we could not detect any changes in the PKC levels in mononuclear cells of primary Sjögren's syndrome and mixed connective tissue disease patients. These results suggest that impaired PKC isoenzyme pattern may exist in the T cells and monocytes of SLE patients. Furthermore, the clinically efficient glucocorticoid application in SLE can increase the expression of some members of PKC system.

Identification of retroviral conserved pol sequences in serum of mixed connective tissue disease and systemic sclerosis patients.

Human endogenous retroviruses (HERVs) expression has been suspected as a factor participating in the development of autoimmune diseases. Employing the dot blot hybridisation, we observed that 90.9% of mixed connective tissue disease (MCTD) (n = 22) patients exhibited the presence of human immunodeficiency virus type 1 (HIV-1) conserved pol sequence in DNA isolated from serum. The same investigation conducted in the group of systemic sclerosis (SSc) (n = 79) patients identified a conserved retroviral pol sequence in 34.6% of antinuclear antibodies (ANA) positive (n = 52) and 40.7% of ANA negative (n = 27) patients. However, 100% of anti-U1-ribonucleoprotein (RNP) positive SSc (n = 9) patients exhibited the presence of HIV-1 conserved pol sequence. Our findings suggest that the presence of retroviral sequence in serum of MCTD and SSc patients may correlate with development of autoimmune response directed against U1-70 kDa polypeptide antigen.

Increased serum angiotensin I-converting enzyme activity in patients with mixed connective tissue disease and pulmonary hypertension.

The relationship between serum angiotensin I-converting enzyme (ACE) activity, a possible marker of pulmonary endothelial injury, and the occurrence of pulmonary hypertension (PH) in patients with mixed connective tissue disease (MCTD) was investigated. Before corticsteroid therapy, the mean serum ACE level was 26.4 +/- 14.0 mU/ml in patients with MCTD and PH (n = 6), 16.8 +/- 4.1 mU/ml in patients with MCTD but without PH (n = 18), 16.8 +/- 4.1 mU/ml in patients with undifferentiated connective tissue disease (n = 14), and 16.5 +/- 3.9 mU/ml in controls (n = 18). No significant difference in the enzyme activity was found among the groups. However, 4 patients with MCTD showed increased ACE levels (> 28.3 mU/ml), and all of them had PH. Our results suggest that elevation of serum ACE activity may be related to the occurrence of PH in patients with MCTD.

Serum adenosine deaminase activity in systemic sclerosis (scleroderma) and related disorders.

BACKGROUND: Adenosine deaminase (ADA) activity in serum is mainly derived from T lymphocytes. OBJECTIVE: Our purpose was to clarify the significance of ADA activity in systemic sclerosis (PSS) and related disorders. METHODS: ADA activity was determined with an enzymatic method in 34 patients with PSS, 4 with mixed connective tissue disease (MCTD), 6 with dermatomyositis (DM), 11 with localized scleroderma (LS), and 13 with other collagen diseases. RESULTS: Serum ADA activity was elevated over the mean (+2 standard deviations) of the control in 85% of the patients with PSS, all with MCTD, 83% of those with DM, and 82% of those with LS. The mean values in 10 PSS patients with anti-topoisomerase I antibodies, 14 patients with anti-RNP antibodies, 12 patients with anticentromere antibodies (ACAs), and 5 patients without antinuclear antibodies (ANAs) were 26.1, 24.9, 22.6, and 16.8 IU/L, respectively. In most cases, except for ACA-positive patients, serum ADA activity changed almost in parallel with ANA titers. CONCLUSION: These results support the notion that T cells are involved in the pathogenesis of PSS and related disorders.

Serum collagenase-like peptidase activity in rheumatoid arthritis and systemic lupus erythematosus.

Collagenase-like (CL) peptidase activity in serum, which was measured using a newly synthesized substrate, (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide, was significantly lower in patients with advanced rheumatoid arthritis or with systemic lupus erythematosus than that in normal controls. Decrease of the serum enzyme activity was more pronounced in systemic lupus erythematosus. No significant change in serum CL-peptidase activity was found in other connective tissue diseases such as mixed connective tissue disease and Sjögren's syndrome.