B Leng

Th1 (IL‐2, interferon‐gamma (IFN‐γ)) and Th2 (IL‐10, IL‐4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE)

We investigated the production of IL‐2, IFN‐γ, IL‐10 and IL‐4 by PBMC from 24 patients with SLE and 10 healthy individuals. Basal and mitogen‐stimulated (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was determined in a whole blood assay (WBA). Supernatants were collected and assayed with specific ELISAs. Although the IL‐2 and IFN‐γ contents did not differ significantly between patients and controls under both conditions, statistically significant correlations were found between each cytokine and disease activity (SLAM index) after stimulation (respectively, r= 0.501, P = 0.01 and r = 0.631, P = 0.001). PBMC IL‐10 production was significantly higher for patients than controls (P = 0.05), but no correlation between IL‐10 levels and the SLAM index was obtained. IL‐4 production was not statistically different between SLE patients and controls. For stimulated WBAs, the IL‐10/IL‐2 and IL‐10/IFN‐γ ratios were significantly correlated with disease severity (P = 0.02; P = 0.001, respectively). Overall, our data suggest that SLE is characterized by an elevated production of IL‐10, reflecting the basal state of activation of the immune system. During exacerbation of SLE, IL‐2 and IFN‐γ are synthesized in larger amounts and may cause the tissue damage observed.

Anti‐platelet antibodies in patients with systemic lupus erythematosus and the primary antiphospholipid antibody syndrome: their relationship with the observed thrombocytopenia

The role of antiphospholipid antibodies in the pathogenesis of the thrombocytopenia observed during primary antiphospholipid antibody syndrome (APAS) and systemic lupus erythematosus (SLE) remains controversial. We have used the MAIPA test to examine the frequency and specificity of anti‐platelet antibodies directed against the major platelet membrane glycoproteins (GP IIb–IIIa, GP Ib–IX, GP Ia–IIa and GP IV) in patients where SLE and APAS were associated or not with thrombocytopenia. Results were compared with a series of 26 ITP patients, 46% of whom were shown to possess anti‐platelet antibodies directed against one or more of the platelet surface glycoproteins. When APAS was associated with thrombocytopenia, 7/10 patients possessed antibodies against GP IIb–IIIa and/or GP Ib–IX. For SLE patients with thrombocytopenia, 6/10 patients were shown to have antiplatelet antibodies against GP IIb–IIIa, GP Ib–IX or GP IV. In contrast, for APAS (n=11) and SLE patients (n=11) without thrombocytopenia, only one patient had an antibody directed against GP IIb–IIIa and one patient had an antibody to GP IV. Our results suggest that antibodies directed against major platelet membrane glycoproteins may play a role in the thrombocytopenia that is seen during SLE and APAS.

Asymptomatic Atherosclerosis in HIV-positive Patients: A Case-control Ultrasound Study

Atherosclerosis has been reported in some HIV-positive subjects without any known risk factor. The purpose of the present study was to investigate cervical arteries, abdominal aorta and femoral arteries by B-mode ultrasonography and doppler in 30 HIV-positive subjects matched to 18 controls for sex, age, tobacco consumption and arterial hypertension. Although no haemodynamically or clinically relevant lesions were found, plaques occurred more often in patients than in controls (11 patients, 36.7% vs. 2, 11.1%; P = 0.05). Compared to the HIV-positive patients without plaques, those with plaques had a tendency to have decreased lower HDL cholesterol, higher tobacco consumption and lower CD4-cell count (77 +/- 85/mm3 vs. 220 +/- 202/mm3). The patients with plaques (but not those without plaques) had lower HDL cholesterol than controls (P = 0.03). Asymptomatic atherosclerosis seems to be more frequent in HIV-positive patients and is associated to lower HDL cholesterol.

Autoantibodies to malondialdehyde-modified epitope in connective tissue diseases and vasculitides

Malondialdehyde (MDA), a peroxidative end‐product released during polyunsaturated fatty acid degradation, reacts strongly with lysine residues of cellular proteins. MDA‐modified proteins become immunogenic and may elicit specific autoantibody formation. We hypothesized that systemic diseases in which inflammatory events occur, could be an interesting model for studying oxidative stress. A few studies have suggested that MDA‐modified proteins may exist in systemic diseases, and that autoantibodies to MDA‐modified structures might reflect this oxidative process. Autoantibodies to MDA‐modified epitope(s) were therefore assayed in sera of patients with systemic lupus erythematosus (SLE, n = 29), scleroderma (SCL, n = 11), giant cell arteritis (GCA, n = 11), periarteritis nodosa (PAN, n = 10), rheumatoid arthritis (RA, n = 9), and healthy subjects (HS, n = 32). Significantly increased anti‐MDA‐modified epitope(s) autoantibodies were found in patients with SLE and also in other systemic diseases such as PAN and SCL. Autoantibodies to MDA‐modified epitope(s) were predominantly of IgM isotype, with low levels of IgG and no IgA activity. In SLE, anti‐MDA‐modified epitope(s) autoantibody titres correlated strongly with systemic lupus activity measure (SLAM, r = 0·702, P = 0·0001), anti‐nuclear antigen autoantibodies (ANA, r = 0·4, P = 0·029), IgG anti‐cardiolipin (r = 0·558, P = 0·03) and the steroid drug regimen (r = 0·52, P = 0·004). Autoantibodies to MDA‐modified epitope(s) may reflect oxidative modifications occurring in systemic diseases, and might be useful as clinical markers of SLE activity if further investigated.

Three cases of acquired von Willebrand disease associated with systemic lupus erythematosus

Acquired von Willebrand disease associated with systemic lupus erythematosus (SLE) has been detected in three middle‐aged women. In each case the first clinical manifestation was a bleeding syndrome. Plasma levels of von Willebrand factor (VWF) and ristocetin‐induced platelet agglutination were as found in type 1 von Willebrand disease for the first patient, type 3 for the second patient, and type 2 for the third patient. Intraplatelet levels of VWF were normal for all three patients. In all cases a mixture of patients plasma with normal plasma resulted in inhibition of ristocetin‐induced binding of VWF to normal platelets. Intravenous immunoglobulin given to patients 2 and 3 corrected the plasma VWF level of the second patient but not that of the third. Therapy with corticosteroids was partially beneficial for patient 3 and patient 2. For patient 2, the severity of the cutaneous lesions also led to the use of cyclophosphamide, and this therapy resulted in total correction of VWF levels. Our observations confirm previous reports of acquired von Willebrand syndrome associated with SLE and show heterogeneity both in the phenotypic form and in the response to treatment.

Atherogen lipid profile in HIV-1-infected patients with lipodystrophy syndrome.

Background: Cases of lipodystrophy syndrome and metabolic disorders have been described since the onset of highly active antiretroviral therapy in HIV-infected patients. The aim of our study was to estimate the prevalence of lipodystrophy (LD) and to define the associated lipid profile of these patients. Methods: The following were determined for each patient: lipid profile (cholesterol and its subfractions, atherogenicity ratios, and triglycerides), blood glucose, and immunovirological markers (CD4(+) cell count and plasma viral load). Patients were classified into two groups on the basis of whether or not they presented with clinical signs of LD. Results: Among 233 HIV-infected patients included in the study, 61 cases (26.1%) of lipodystrophy (LD) were noted. Compared with non-LD patients (NLD), LD patients were older men (P<10(-4)) with a lower CD4(+) lymphocyte cell count (P<0.007) and more often at the AIDS stage (P<10(-3)) (OR=3.2 (95% CI: 1.47-6.2)). Multivariate analysis showed a correlation between LD cases and age (10 years older) (OR=1.78 (95% CI: 1.23-2.57), P<0.002) and the decrease in CD4(+) cell count (100 CD4(+)/mm(3) lower) (OR=1.31 (95% CI: 1.09-1.58), P<0.004). An analysis of lipid subfractions and atherogenicity ratios clearly indicated a proatherogenic lipid profile for the LD patients. Conclusions: The underlying physiopathological mechanism of LD is still unknown. However, the lipid profile of HIV-1-infected patients with a LD syndrome appears to place these patients at an increased risk of progression of atherosclerosis.

Severe pancytopenia triggered by recombinant hepatitis B vaccine

We describe the case of a teenager who developed fever, arthritis, cutaneous vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late myeloid elements and, subsequently, maturation arrest. Interferon‐γ (IFN‐γ) production by peripheral blood mononuclear cells from the patient was dramatically increased. An underlying immune predisposition (HLA‐DR3) may have indirectly enabled the vaccine to trigger a hepatitis B virus‐specific cytotoxic T‐lymphocyte response. It is therefore possible that the pancytopenia was induced by a dysregulation of the CD8+ T‐cell compartment via increased IFN‐γ production.

Foscarnet decreases HIV-1 plasma load.

OBJECTIVE To evaluate the effect of foscarnet on HIV-1 replication in vivo. PATIENTS AND METHODS Seventeen AIDS patients with cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus (VZV) infection, Kaposis sarcoma (KS), or a combination of these were treated with foscarnet. HIV RNA quantification (bDNA 2.0, Chiron, Emeryville, CA, U.S.A.), CMV pp65 antigenemia (Argene Biosoft, Varilhes, France), and CMV viremia were determined before and during therapy. RESULTS Four patients had CMV retinitis (1 with KS), 2 patients had CMV pneumonia (1 with KS), 1 patient had CMV cholecystitis, 2 patients had VZV infection (1 with KS), 1 patient had HSV-2 infection, and 7 patients had KS alone. The decrease in HIV-1 load was -0.73 +/- 0.39 log copies/ml (p = 2.10(-6)) after 3 days of treatment and -1.15 +/- 0.49 log copies/ml (p < 10(-7)) after 10 days of treatment, compared with day 0. Furthermore, reduction of HIV-1 plasma load during foscarnet therapy did not depend on the presence or absence of CMV disease or on a positive pp65 antigenemia at day 0. CONCLUSION We observed decreased HIV-1 plasma load in all patients treated with foscarnet, regardless of presence or absence of clinical or biologic CMV infection. This decrease supports the proposition that foscarnet anti-HIV-1 activity may be of clinical importance.

Extensive brain calcifications in systemic sclerosis: two cases

Systemic sclerosis (scleroderma) is a multisystem connective tissue disease of unknown aetiology, characterised by progressive fibrosis of the skin and internal organs including the lungs and gastrointestinal tract.1 Pathological calcification of soft tissues (known as calcinosis) is a common feature in the CREST syndrome of scleroderma (calcinosis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia). By contrast, internal organ calcification is rare, and isolated cases of spinal calcinosis and calcific constrictive pericarditis have been reported.2 3 We report here the cases of two patients with systemic sclerosis whose CT examination disclosed extensive brain calcifications. Case 1, a 48 year old man was referred to hospital because of polyarthralgia involving the wrists and ankles, Raynaud’s phenomenon, and tightness of hand skin. The patient’s wife had noticed that during the previous months, he had a slowed mentation and a depressive mood. Physical examination disclosed a sclerodactyly but no telangiectasias. Routine haematological tests were normal. Antinuclear antibodies were positive at a 1/2000 dilution with nucleolar fluorescence. Rheumatoid factors, antidouble stranded DNA and antiphospholipid antibodies were negative. There was no cryoglobulinaemia. Complement was normal. Lung function tests showed a restrictive syndrome (forced vital capacity=75% predicted). Chest radiography was normal, as were oesophageal manometry and cardiac ultrasonographic examination. A diagnosis of systemic sclerosis …

Acides gras membranaires et anti-oxydants sériques chez 77 patients infectés par le VIH

We have measured the fatty acid (FA) composition of erythrocyte membranes and plasma anti-oxidants in HIV+ patients. Saturated FA are higher and poly-unsaturated FA lower than in controls (P = 0.02). Selenium (Se) is lower in patients less than 400 CD4 cells/mm3 (P = 0.002). Vitamin A is lower in the HIV+ regardless of the CD4 cell count. Se and vitamin A are correlated to nutritional markers (body mass index and albumin).