Atsuko Murashima

Etanercept during pregnancy and lactation in a patient with rheumatoid arthritis: drug levels in maternal serum, cord blood, breast milk and the infant’s serum

Women with rheumatoid arthritis (RA) appear to be at a high risk of preterm delivery, preeclampsia and low birth weight infants.1 Reduction of inflammatory activity is of particular importance in those desirous of having children.2 3 The use of disease-modifying antirheumatic drugs, including biological preparations, has been shown to be essential for suppression of the activity of RA. Tumour necrosis factor inhibitors have been introduced for the treatment of RA, with the expectation of obtaining immediate and certain effect. Although no teratogenicity of these drugs has been recognised in animal experiments,4 5 the safety of their use in pregnancy has not yet been adequately established. In this …

Relation between soluble interleukin 2 receptor and clinical findings in patients with systemic lupus erythematosus.

The concentration of soluble interleukin 2 receptor (IL-2R) was determined in the serum of 54 patients with systemic lupus erythematosus (SLE) by an enzyme linked immunosorbent assay (ELISA) using two monoclonal antibodies with the IL-2R. Concentrations of soluble IL-2R in the serum of the patients with SLE (study group) were significantly higher than in 20 normal subjects (control group). The relation between concentrations of soluble IL-2R and clinical findings was investigated. The concentration of soluble IL-2R showed no particular relation with the clinical manifestations and did not correlate with the level of anti-DNA antibody or CH50. Significant correlation between the concentration of soluble IL-2R and disease activity did exist, however. Furthermore, the concentration of soluble IL-2R in some cases changed simultaneously with the disease activity. Thus the concentration of soluble IL-2R may serve as a new clinical indicator of disease activity in patients with SLE.

Relationship of Th1/Th2 cell balance with the immune response to influenza vaccine during pregnancy

To determine the optimal timing for influenza vaccination in pregnant women, we measured alterations in the types 1 and 2 T helper cell (Th1/Th2) balance during pregnancy, monitored specific immunity to inoculated antigens after vaccination with inactivated influenza vaccine, evaluated the relevance of the Th1/Th2 ratio and immune responses to the vaccination, monitored the maintenance of high antibody titers until delivery and measured the transplacental antibody transfer rate. No significant alterations of the Th1/Th2 balance were noted in the 65% of pregnant women among whom the Th1/Th2 ratio was lower than 9.9% in the first trimester. In those groups with a ratio higher than 10% in the first trimester, there was a tendency for the ratio to decrease as gestation advanced. The efficiency of immunization was not influenced by the Th1/Th2 status or by the stage of gestation. The antibody titer decreased steadily with time from 1 month after vaccination to the time of delivery. Conversely, the transfer rate of antibodies from maternal to fetal blood at the time of delivery increased with the duration of gestation after vaccination. Nevertheless, the antibody titers in both maternal and fetal blood were sufficient to afford protection against infection. Thus, efficient influenza vaccination can be undertaken at any stage of pregnancy. J. Med. Virol. 81:1923–1928, 2009.

Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to proliferating cell nuclear antigen in active lupus patients

Hybridoma producing monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) (TOB7, IgG1 κ) was newly established. Using TOB7, PCNA was detected in the peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). Forty-four of 58 patients with SLE had PBMC expressing PCNA. The percentage of PCNA-positive PBMC in patients with SLE was 0–20% (mean: 2.63%) which was significantly higher (P<0.01) compared with normal controls (mean: 0.18%), patients with rheumatoid arthritis (mean: 0.83%), and patients with mixed connective tissue disease (mean: 0.38%). Patients with high numbers of PCNA positive PBMC tended to complicate pulmonary disorders (P<0.005), especially pulmonary fibrosis (P<0.005). In addition, the percentage of PCNA-positive cells in SLE patients correlated with the disease activity (r=0.45,P<0.01). The lymphocyte subsets of PCNA-positive PBMC were examined, and most of those cells belonged to CD4- or CD8-positive T-cell populations in three lupus patients. Our findings indicate that PCNA-positive activated PBMC are present in SLE patients and the percentage of PCNA-positive PBMC may be used as an indicator of disease activity.

Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a pregnant patient.

BACKGROUND: Uncontrolled phagocytosis of normal hemopoietic cells by activated histiocytes in bone marrow is collectively referred to as hemophagocytic lymphohistiocytosis. CASE: We present a case of hemophagocytic lymphohistiocytosis associated with herpes simplex virus-2 infection in the second trimester. Cytopenia, elevated C-reactive protein, ferritin, soluble interleukin-2 receptor, and interleukin-6 with high-grade fever were observed following genital herpes infection, and the existence of hemophagocytes in bone marrow confirmed the diagnosis of hemophagocytic lymphohistiocytosis. Corticosteroid therapy failed to arrest the hemophagocytic process, whereas cyclosporin A was effective. The patient delivered a healthy infant after remission and has not experienced exacerbation. CONCLUSION: It is often important to take into consideration hemophagocytic lymphohistiocytosis when encountering cytopenia with high-grade fever. Cyclosporin A was a safe and available strategy for this corticosteroid-resistant case.

Very low-dose cyclosporin treatment of steroid-resistant interstitial pneumonitis associated with Sjögren's syndrome.

Cyclosporin is known to be effective for both transplantation and a spectrum of immune-mediated diseases. Because this agent also causes severe adverse effects, especially nephrotoxicity, careful monitoring is required for the development of such reactions. Here we report the successful treatment with extremely low-dose cyclosporin (1 mg/kg/day) of a patient who had steroidresistant interstitial pneumonitis and Sjögrens syndrome.

Efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy.

OBJECTIVE: To evaluate the efficacy of double vaccination with the 2009 pandemic influenza A (H1N1) vaccine during pregnancy. METHODS: A study of the 2009 H1N1 vaccine was conducted in 128 pregnant women, who were between 8 and 32 weeks of gestation in October 2009, to monitor the immune response to vaccination and the change in antibody positivity rate and to assess the immune response. Furthermore, the study aimed to assess the changes in these parameters after the first and second vaccination, monitor the maintenance of antibody titers in maternal blood, assess antibody transfer to umbilical cord blood, and evaluate the vaccine. RESULTS: The antibody positivity rate increased from 7.2% before vaccination to 89.5% after the second vaccination. The vaccine was efficacious, producing a sufficient immune response in 90% of patients, regardless of the stage of gestation. The antibody titers were maintained until delivery, and were higher in umbilical cord blood at delivery than in maternal blood. Although the second vaccination increased the antibody titers in 27% of patients, and the antibody titers in maternal and umbilical cord blood at delivery tended to be higher in the double vaccination group than in the single, the differences were not statistically significant. CONCLUSION: Single vaccination induces sufficient immune response and transfer of immunity to the fetus in pregnant women with no pre-existing antibodies. LEVEL OF EVIDENCE: III

Subsets of Activated T Cells in Patients with Systemic Lupus Erythematosus: the Relation to Cell Cycle

The correlation among the various markers of activated T cells (soluble interleukin 2 receptor (sIL-2R), HLA-DR+ and HLA-DP+ T cells, proliferating cell nuclear antigen (PCNA) positive lymphocytes) were examined in patients with systemic lupus erythematosus (SLE), and related to the cell cycle. The concentration of sIL-2R and the proportion of HLA-DR+ T cells, HLA-DP+ T cells or PCNA+ lymphocytes were increased significantly as compared to that in normal subjects. And, the concentrations of sIL-2R correlated with the proportions of PCNA+ lymphocytes, but not with the proportions of HLA-DR+ T cells, HLA-DP+ T cells. The correlation between sIL-2R and PCNA+ lymphocytes was attributed to both indicators being increased during the G1B or S phase in normal T cells upon stimulation by phytohemagglutinin (PHA). Upon cell cycle analysis it was learned that activated T cells could be found in the G1A and the S phases.

Primary prophylaxis to prevent obstetric complications in asymptomatic women with antiphospholipid antibodies: a systematic review.

Objective Obstetric complications are common in patients with antiphospholipid syndrome. However, the impact of antiphosholipid antibodies (aPL) in the pregnancy outcomes of asymptomatic aPL carriers is uncertain. The aim of this systematic review is to assess whether primary prophylaxis is beneficial to prevent obstetric complications during pregnancy in asymptomatic women positive for aPL who have no history of recurrent pregnancy loss or intrauterine fetal death. Methods Studies evaluating the effect of prophylactic treatment versus no treatment in asymptomatic pregnant aPL carriers were identified in an electronic database search. Design, population and outcome homogeneity of studies was assessed and meta-analysis was performed. The pooled Mantel–Haenszel relative risk of specific pregnancy outcomes was obtained using random effects models. Heterogeneity was measured with the I2 statistic. All analyses were conducted using Review Manager 5.3. Results Data from five studies involving 154 pregnancies were included and three studies were meta-analysed. The risk ratio and 95% confidence interval (CI) of live birth rates, preterm birth, low birth weight and overall pregnancy complications in treated and untreated pregnancies were 1.14 (0.18–7.31); 1.71 (0.32–8.98); 0.98 (0.07–13.54) and 2.15 (0.63–7.33),respectively. Results from the meta-analysis revealed that prophylactic treatment with aspirin is not superior to placebo to prevent pregnancy complications in asymptomatic aPL carriers. Conclusion This systematic review did not find evidence of the superiority of prophylactic treatment with aspirin compared to placebo or usual care to prevent unfavourable obstetric outcomes in otherwise healthy women with aPL during the first pregnancy.

Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.

Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study (n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0–29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR–) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6–16), p < 0.0001. Sensitivity, specificity, LR + and LR– for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.