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.
Summary. 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-g (IFN-g) 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 1 T-cell compartment via increased IFN-g production.Keywords: hepatitis B vaccine, pancytopenia, lupus, interferon-g, CD81 T cells.Hepatitis B vaccine produced by genetic engineering technology is a safe and efficient means of preventing hepatitis B virus (HBV) infection and its possible chronic sequel. Although it is widely used, haematological abnormalities have rarely been described and include only thrombocytopenia and Evans' syndrome (Martinez & Domingo, 1992;Poullin & Gabriel, 1994). Here, we report on a teenage girl who presented with fever, polyarthritis, cutaneous vasculitis and severe pancytopenia that occurred 3 weeks after the third booster dose of recombinant hepatitis B vaccine. CASE REPORTA 16-year-old girl was referred to the Internal Medicine Clinic in May 1998 for fever, maculopapular rash and polyarthritis that had begun 15 d earlier. Three weeks before the onset of symptoms, she had received the third dose of recombinant hepatitis B vaccine (GenHevac, Pasteur Vaccines). At presentation (d 15), she was febrile (408C) and had severe polyarthritis and a diffuse pruritic maculopapular rash. Laboratory analyses revealed: pancytopenia (haemoglobin, 8 g/dl; platelet count, 30 Â 10 9 /l; leucocyte count, 0´7 Â 10 9 /l; neutrophils, 0´2 Â 10 9 /l); hepatic cytolysis (aspartate aminotransferase, 196 U/l; normal range 7± 40 U/L; alanine aminotransferase, 236 U/l; normal range 5±50 U/l); erythrocyte sedimentation rate of 80 mm/h; a negative direct Coombs' test and absence of antibodies directed against platelets; normal haptoglobin; complement activation with a low C4b level; polyclonal hypergammaglobulinaemia and high b2-microglobulin (3´20 mg/l; normal range 1´2±2´5 mg/l); antinuclear antibody (ANA) titre of 1:8000 without specificity; anti-hepatitis B surface antigen (HBs) antibody titre of 200 mIU/ml, but no circulating HBs antigen; negative serology for cytomegalovirus, Epstein±Barr virus, human immunodeficiency virus, hepatitis A and hepatitis C viruses. Absolute CD4 1 and CD8 1 T-lymphocyte counts were low (0´131 Â 10 9 /l and 0´302 Â 10 9 /L; normal range 0´7±1´1 and 0´6± 0´9 Â 10 9 /l respectively). Sixty per cent of the T CD3 1 lymphocytes expressed DR antigen at their surface, suggesting they were activated, and most of them belonged to the CD3 1 CD4 2 CD8 1 DR 1 phenotype. The HLA class II types were DR1/3 and DQ5/7. A skin biopsy specim...
Granulosa cell tumors (GCT) are ovarian neoplasms that tend to recur and spread in the pelvis and the abdomen several years after the initial treatment. Anti-Mülerian hormone (AMH) is a reliable serum marker of these tumors. To enhance the availability and the sensitivity of serum AMH determination, we developed an ultrasensitive enzyme-linked immunosorbent assay. In this work we compare the results of serum AMH levels, obtained using the ultrasensitive and the traditional assays, in 31 patients with ovarian GCT followed up for up to 7 yr. The ultrasensitive enzyme-linked immunosorbent assay has a significantly higher sensitivity than the traditional one. This resulted in the detection of low serum AMH levels, which were undetectable with the traditional assay, in several cases including one patient in whom a recurrence of a GCT had developed and two patients in whom the treatment had not been completely successful. These cases highlight the importance of the availability of a highly sensitive assay allowing evaluation with high precision of the results of treatment and to detect the recurrences of GCT at an early, preclinical stage.
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