Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis.

BACKGROUND: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ involvements or cutaneous subgroups of SSc patients. METHOD: MPs in platelet-poor plasma from 121 patients with SSc, 79 and 42 with limited and diffuse cutaneous disease, respectively, were characterized by flow cytometry for their capacity to bind annexin V in combination with surface markers of either platelets (PMPs), leukocytes (LMPs) or endothelial cells (EMPs). Soluble E- and P-selectin levels were determined in plasma. By correlation analyses, this was held against involvement of skin, lung function, lung fibrosis, pulmonary artery hypertension, and serology. RESULTS: None of the markers were associated with cutaneous subgroups of SSc. Concentrations of annexin V non-binding EMPs and annexin V non-binding LMPs were negatively correlated to pulmonary diffusing capacity (DLCO) (r = -0.28; p = 0.003; r = -0.26; p = 0.005) and forced vital capacity (FVC) (r = -0.24; p = 0.009; r = -0.29; p = 0.002), driven by patients with limited and diffuse cutaneous disease, respectively. Soluble E-selectin levels correlated negatively to DL(CO) (r = -0.21, p = 0.03) and FVC (r = -0.25; p = 0.007); and soluble P-selectin correlated negatively to DL(CO) (r = -0.23, p = 0.01). CONCLUSION: Negative correlations between annexin V non-binding EMP and LMP concentrations with lung function parameters (DL(CO) and FVC) differed between limited and diffuse cutaneous subsets of SSc, indicative of various pathogeneses of lung involvement in SSc, possibly with a differential role of MPs.

[Development of scleroderma renal crisis in a patient with undiagnosed scleroderma].

Less than 10% of the patients with systemic scleroderma develop renal crisis, i.e. acute renal failure and severe hypertension in most cases. Kidney biopsy shows hypertensive arteriolar changes. This complication was lethal until treatment with captopril was introduced in 1976. Since that time the survival of the patients has improved. If treatment is started early, further deteoriation of the kidney may be prevented.

Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis.

Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according to gender, age, height, and weight. The yearly changes in VC and DLco were calculated, Delta VC and Delta DLco, respectively. IgM RF was measured at the beginning of the study. Smoking was defined as having ever smoked. Statistically significant deterioration of VC and DLco in patients with circulating IgM RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association and whether the presence of IgM RF in smoking patients with SSc actually confers an increased risk of pulmonary damage remains to be determined.

Prognostic factors in lupus nephritis: diagnostic and therapeutic delay increases the risk of terminal renal failure.

OBJECTIVE: To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis. METHODS: Ninety-one patients with lupus nephritis were included in the study. Renal biopsies were classified according to the WHO criteria and examined for the presence of active and chronic histological changes. Predictors of endstage renal disease (ESRD) were identified by univariate and multivariate analyses. RESULTS: The median followup time was 6.1 years (0.1-30.0 yrs). In all cases, immunosuppressive treatment was initiated or intensified within one month following renal biopsy. The cumulative incidence of ESRD after 1, 5, and 10 years was 3.5%, 15%, and 17%, respectively. A variety of clinical and biopsy findings including several histological markers of chronic renal damage were identified as univariate predictors of ESRD. In multivariate regression analyses, duration of nephritis symptoms > 6 months prior to biopsy, s-creatinine > 140 micromol/l, diffuse proliferative glomerulonephritis, and tubular atrophy emerged as the strongest combination of independent risk factors (relative hazard ratios: 9.3, 5.6, 8.9, and 3.1, respectively). CONCLUSION: Our results confirm the negative prognostic impact of hypercreatininemia, class IV histopathology, and tubular atrophy in lupus nephritis. Our data show that delay between onset of nephritis and renal biopsy constitutes an important risk factor of ESRD. Patients with SLE should have kidney biopsy as soon as clinical signs of nephritis are evident in order to accelerate treatment decisions and minimize risk of inflammation-induced irreversible kidney damage.