BackgroundLymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features in systemic lupus erythematosus (SLE). We speculate whether lymphocyte subset counts are ...affected by pregnancy and if they relate to autoantibody profiles and/or IFN alpha protein in SLE pregnancy.MethodsRepeated blood samples were collected during pregnancy from 80 women with SLE and 51 healthy controls (HC). Late postpartum samples were obtained from 19 of the women with SLE. Counts of CD4 + and CD8 + T cells, B cells and NK cells were measured by flow cytometry. Positivity for anti-nuclear antibodies (ANA) fine specificities (double-stranded DNA dsDNA, Smith Sm, ribonucleoprotein RNP, chromatin, Sjogren's syndrome antigen A SSA and B SSB) and anti-phospholipid antibodies (cardiolipin CL and beta 2 glycoprotein I beta 2GPI) was assessed with multiplexed bead assay. IFN alpha protein concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.ResultsWomen with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principal component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chromatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-beta 2GPI), IFN alpha protein levels and disease activity. CD4 + T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4 + T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4 + T cell count was lower in IFN alpha protein positive relative to negative women. Finally, CD4 + T cell count was unrelated to treatment.ConclusionLymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFN alpha protein levels and disease activity, which could be due to divergent disease pathways.
ObjectivesAdverse pregnancy outcomes (APOs) are more common among women with SLE compared to the general population and the underlying immunopathological mechanisms are largely unknown. The type I ...interferon (IFN) signature persists in complicated SLE pregnancies, while it is downregulated in uncomplicated SLE pregnancies. Moreover, IFNα protein concentrations are higher in SLE compared to healthy pregnancies, but whether IFNα protein levels are associated with APOs in SLE is unknown. The aim of this study was to evaluate whether APOs are more common in Swedish women with SLE compared to healthy controls, and if this associates with circulating IFNα protein or autoantibodies.MethodsWe included 83 births from 77 women with SLE and 58 births from 58 healthy controls (HC). Repeated peripheral blood samples were collected and IFNα protein levels were quantified with Simoa. Anti-nuclear antibody (ANA) specificities and anti-phospholipid antibodies (aPL) during pregnancy was analysed using multiplexed bead technology. APOs were defined as an infant small for gestational age (SGA), preterm birth, low birth weight (LBW) and/or preeclampsia. Multivariate orthogonal partial least squares analysis (OPLS) was used to examine SGA, LBW and/or preterm (combined outcomes, Y-variable) in relation to mean IFNα protein level, IFNα positivity, ANA specificity and aPL positivity during pregnancy.ResultsAPOs were more common in women with SLE compared to healthy women (33% compared to 12%, p=0.005). The most common outcome was SGA, which was present in 17% of women with SLE compared to 3% of HC (p=0.01). In OPLS, SGA, LWB and/or preterm birth was most positively associated to mean IFNα protein level and IFNα positivity in plasma during pregnancy. Preeclampsia was unrelated to IFNα and autoantibody positivity in women with SLE. In univariate analysis, the mean IFNα protein level was significantly higher in women with SLE who had an infant who was SGA, LBW and/or preterm compared to women without these APOs.ConclusionIFNα protein level in plasma is a potential risk factor for giving birth to an infant who is small for gestational age, has low birth weight and/or is delivered preterm in SLE.
ObjectiveAdverse pregnancy outcomes are more common among women with systemic lupus erythematosus (SLE) compared to healthy women, but there is limited understanding on how pregnancy affects the ...immune system and what specific immunopathological processes that precede these complications. Lymphopenia, autoantibodies and activation of the type I interferon (IFN) system are common features SLE. We aimed to investigate the impact of pregnancy on lymphocyte subset counts in SLE and their associations with autoantibody profiles and IFNα concentrations.MethodsRepeated blood samples were collected from 80 pregnant women with SLE and 51 healthy controls (HC), with additional samples from 19 women with SLE postpartum. Flow cytometry was used to measure CD4+ and CD8+ T cells, B cells, and NK cells. Positivity for anti-nuclear antibodies (ANA) fine specificities and anti-phospholipid antibodies was assessed using multiplexed bead assay. IFNα concentration was quantified with Single molecule array (Simoa) immune assay. Clinical data were retrieved from medical records.ResultsWomen with SLE had lower counts of all lymphocyte subsets compared to HC throughout pregnancy, but counts did not differ during pregnancy compared to postpartum. Principle component analysis revealed that low lymphocyte subset counts differentially related to autoantibody profiles, cluster one (anti-dsDNA/anti-Sm/anti-RNP/anti-Sm/RNP/anti-chormatin), cluster two (anti-SSA/anti-SSB) and cluster three (anti-CL/anti-β2GPI), IFNα protein levels and disease activity. CD4+ T cell counts were lower in women positive to all ANA fine specificities in cluster one compared to those who were negative, and B cell numbers were lower in women positive for anti-dsDNA and anti-Sm compared to negative women. Moreover, CD4+ T cell and B cell counts were lower in women with moderate/high compared to no/low disease activity, and CD4+ T cell count was lower in IFNα protein positive relative to negative women. Finally, CD4+ T cell count was unrelated to treatment.ConclusionLymphocyte subset counts are lower in SLE compared to healthy pregnancies, which seems to be a feature of the disease per se and not affected by pregnancy. Our results also indicate that low lymphocyte subset counts relate differentially to autoantibody profiles, IFNα protein levels and disease activity, which could be due to divergent disease pathways.
To investigate the incidence of uveal melanoma in Sweden during the period from 1960 to 1998, with respect to age distribution, gender, and changes in incidence over time.
The Swedish Cancer Registry ...was searched for patients with uveal melanoma and cross-checked against hospital files over patients where an eye-sparing treatment had been applied, to ensure inclusion in the Registry even when no histologic specimen was available. The crude and age-standardized incidence was estimated separately for each gender. The Swedish population of 1970 to 1974 was used as a standard, and the annual change in incidence was calculated by using a regression model with logarithmic incidence numbers.
In total, 2997 patients met the criteria, of whom 1542 were males and 1455 females. During the 39-year period, the age-standardized incidence of uveal melanoma declined significantly in the male population, from 11.7 cases/million to 8.4 cases/million (P = 0.002). The trend toward reduced incidence in females, from 10.3 to 8.7 cases/million did not reach statistical significance (P = 0.108). The annual relative change in incidence was 1% (95% CI, 0.8%-1.2%) in males and 0.7% (95% CI, 0%-1.3%) in females. The age-specific incidence revealed a significantly higher incidence among men older than 45 years (23.5 cases/million) compared with the incidence in women of the same age group (19.2 cases/million; P < 0.001).
A Swedish national survey performed to establish the incidence of uveal melanoma during the period from 1960 to 1998 revealed a decreasing incidence in the male and a stable incidence in the female population.
This experimental study investigated differences in perceived restorativeness, mood, attention capacity and physiological reactions when visiting city and forest environments. Twenty female patients ...diagnosed with exhaustion disorder visited three different forest environments and one city environment in randomized order. They performed a standardized 90-min test procedure in each of these environments. Evaluation of the environments and psychological effects in mood were studied with self-administered questionnaires. Attention capacity was studied with Necker Cube Pattern Control task. Physiological responses were measured with regularly scheduled controls of heart rate and blood pressure, and a single test of heart rate recovery. Visits to the forest environments were perceived as significantly more restorative, enhancing mood and attention capacity compared to the city. This also applies to the results of heart rate and to some extent to the results of the diastolic blood pressure. The results from this experimental study support our hypothesis that short visits to forest environments enhance both psychological and physiological recovery and that visits to forest environments are likely to be beneficial when suffering from exhaustion disorder.
To investigate the crude and relative survival rates in patients with uveal melanoma in Sweden during the period from 1960 to 1998.
A population-based national survey revealed 2997 cases of uveal ...melanoma in the Swedish Cancer Registry. The survival rates were calculated by the Hakulinen life-table method, using relative survival as an estimate for deaths due to uveal melanoma. The excess mortality rates were calculated with confidence intervals for the first 15 years after diagnosis. Multivariate regression analysis was undertaken to evaluate the influence of gender, age, and calendar period on relative survival the first 5 years after diagnosis. The underlying causes of deaths in the patients with uveal melanoma, as found in the Cause of Death Registry were also investigated.
Up to December 31, 1998, 2003 patients had died. The 5-year crude survival rate was 60.3% and the relative survival 70.1%. After 10 years, the rates were 42.5% and 59.4%, respectively. Significant excess mortality existed up to 5.5 years after diagnosis. In the multivariate model, younger age (P < 0.001) and later calendar period (P = 0.002), but not gender (P = 0.117), were associated with better relative survival. Deaths due to uveal melanoma were misclassified in the Cause of Death Registry in more than half of the cases.
This study, covering more than 95% of the uveal melanoma cases in the Swedish population revealed an improvement in relative survival rates for patients with uveal melanoma over time and a significant excess mortality up to 5.5 years after diagnosis.
Highlights • We have identified a QRFP peptide-receptor pair in the amphioxus genome. • Pharmacological study confirmed that the cloned QRFP receptor can be activated by the amphioxus QRFP peptide. • ...The amphioxus QRFP receptor can also be activated by human QRFP peptides, 43RFa and 26RFa with high potencies.
To determine the long-term incidence of postirradiation hypothyroidism (HT) in patients with head-and-neck cancer.
The incidence of overt HT was assessed prospectively in 391 patients with nonthyroid ...head-and-neck cancer admitted for radiotherapy (RT) consecutively between 1990 and 1996. Eighty-three patients were excluded from the analysis because of known thyroid disease before treatment (
n = 27), no RT was given (
n = 15), or inadequate follow-up (
n = 41). Overt HT was defined as increased thyroid-stimulating hormone (TSH) in combination with decreased fT4/T4 or in combination with initiation of thyroxine replacement therapy.
With a median follow-up of 4.2 years (range, 3 months to 10.9 years) for 308 evaluable patients, the 5- and 10-year Kaplan-Meier actuarial risks of HT were 20% and 27%, respectively. The median time until development of HT was 1.8 years (3 months to 8.1 years). Multivariate analysis showed that patients with bilateral RT to the neck had a higher risk of HT in comparison with unilateral neck RT (relative hazard, 0.37;
p = 0.02). The addition of surgery to RT increased the overall risk of HT (
p < 0.001); and if surgery involved the thyroid gland, the relative hazard was 4.74 (
p < 0.001). For an elevated pre-RT TSH value, the relative hazard was 1.58 (
p < 0.001).
The incidence of overt HT after locoregional RT for nonthyroid head-and-neck cancer continues to increase with time, even after long-term follow-up. We recommend life-long TSH testing in these patients.
Diffusion anisotropy monitored with diffusion-weighted magnetic resonance imaging (DWMRI) is a sensitive marker to monitor developmental or pathological microstructural changes in spinal cord. The ...white matter is often treated as a unidirectional axonal bundle but collateral fibers branching off the main spinal pathways contradicts this assumption and affects the diffusion anisotropy. It is the aim of this study to investigate to what extent collateral fibers are apparent in diffusion tensor data and if collaterals can be detected as individual fiber directions using crossing fiber detection techniques. We calculate the diffusion tensor and the persistent angular structure (PAS), a multi-fiber reconstruction technique, from high quality post mortem data of a perfusion-fixed vervet monkey cervical spinal cord sample and simulated crossing fiber data. Our results show that (i) cylindrical geometry in the white matter of the spinal cord is an invalid assumption due to collateral fibers. We also demonstrate that (ii) collateral fibers can be resolved as distinct peaks in the water diffusion propagator in white matter using multi-fiber models. Finally, we show that (iii) crossing fibers are mainly located laterally and increase towards the cervical enlargement.
► A method for investigating spinal collaterals from diffusion MRI data. ► Post mortem data from a full cervical monkey spinal cord is presented. ► Collateral frequency increase in the arm and hand area of the cervical enlargement.
Highlights ► The Western clawed frog has six of the ancestral seven gnathostome receptors. ► Binding studies show interesting differences to mammals in peptide–receptor preferences. ► The peptides ...and receptors are widely expressed, notably in skin. ► NPY was detected in brain like in all other vertebrates investigated. ► PYY was not detected in brain, as in mammals but in contrast to fish, nor was PP.
