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Objective: Defective expression of Ras guanil releasing protein-1 (RasGRP-1) and increased apoptosis have been reported in lymphocytes from SLE patients. Whether these aberrations are correlated and linked to disease activity has not been elucidated. Methods: Expression of normal 90 kDa RasGRP-1, its most prevalent 86 kDa isoform and full PARP-1 116 kDa and its cleavage fragment 84 kDa were determined in whole protein lysates of peripheral blood mononuclear cells (PBMC) in correlation with mitogen activated protein kinase (MAPK) activity and SLE clinical status in a large group of SLE patients during 1 year follow-up. Results: Expression of normal 90 kDa RasGRP-1 was comparable in patients and controls. However, SLE patients demonstrated a constitutively increased 86 kDa/90 kDA ratio (p < 0.01) and decreased full poly (ADP-ribose) polymerase protein-1 (PARP-1) expression (p < 0.002) compared with controls who were disease-independent. A remission in disease activity was associated with decreased RasGRP-1 expression. Expression of 84 kDa PARP-1 cleavage fragment was found in 15% of patients but in none of the controls. In addition, expression of PARP-1 correlated positively with normal 90 kDa RasGRP-1 expression and negatively with the RasGRP-1 86 kDa/90 kDA ratio. Conclusions: These data suggest that constitutive aberrant expression of PARP-1 and RasGRP-1 ratio may act in concert to impair survival of lymphocytes in SLE patients. [ABSTRACT FROM AUTHOR]

The association of the antiphospholipid syndrome with malignancy has been extensively reported. Raynaud's phenomenon has also been reported to be associated with various malignancies. In this report, we describe two patients who presented with severe digital ischemia mimicking Raynaud's phenomenon. The patients were found to have antiphospholipid syndrome, and upon extensive evaluation, a diagnosis of a malignancy was made. This report highlights the importance of malignancy workup in patients with severe digital ischemia associated with antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated. Mean patient age was 29.5 ± 4.7 years, and mean disease duration, 6.3 ± 6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-β2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients' children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine. We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE. [ABSTRACT FROM AUTHOR]

Although a few reports in recent years have suggested that patients with antiphospholipid antibodies (aPL) are prone to developing primary anetoderma (PA), it is still unclear how often aPL are detected in unselected PA patients. We studied nine consecutive PA patients for the presence of autoimmune antibodies and disorders in general and the presence of aPL in particular. Six of the nine patients had clinical evidence of associated autoimmune disorders (Graves'disease and autoimmune haemolysis in one, systemic scleroderma in one, Hashimoto's thyroiditis in one, alopecia areata in one) and/or signs of hypercoagulability (recurrent fetal loss in two, recurrent strokes in one, recurrent deep vein thrombosis in one). In four of these six patients the onset of PA preceded these signs. Positive aPL was found in all: anticardiolipin (aCL)in six, anti-β[sub 2]-glycoprotein-I(aβ[sub 2]GPI) in six and lupus anticoagulant (LAC) in four. The most frequent isotype was IgA. Among other autoantibodies found the most frequently was antinuclear antibodies. Four of the nine patients fulfilled the criteria for antiphospholipid syndrome (APS). It is concluded that PAis an important cutaneous sign for autoimmune disorders in general and the presence of aPL in particular. Hence, the work-up of these patients should include testing for LAC as well as for all different isotypes of aCL and a β[sub 2]GPI. We recommend that PA be added to the list of the cutaneous manifestations of APS. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus-associated irreversible organ/system damage was previously associated with various clinical and demographic features. We analysed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) in a cohort of 151 Israeli patients followed for a mean (± s.d.) period of 45.7 ± 37.4 months. Mean score of SLICC/ACR DI at the first and last encounters were 0.17 ± 64 and 1.64 ± 2.1, respectively (P < 0.0001). Multiple logistic regression analyses disclosed a statistically significant positive correlation with corticosteroid and cyclophosphamide therapy. Hydroxychloroquine therapy was significantly associated with lower SLICC/ACR DI. Although the size of our study group did not allow us to find specific organs/systems which were associated with the protective effect of hydroxychloroquine, we suggest this is due to the antiatherogenic effects attributed to antimalarial therapy in SLE. [ABSTRACT FROM AUTHOR]