Positive Impact of Levothyroxine Treatment on Pregnancy Outcome in Euthyroid Women with Thyroid Autoimmunity Affected by Recurrent Miscarriage

Impaired thyroid hormone availability during early pregnancy is associated with recurrent miscarriage (RM) and adverse pregnancy outcomes. The main cause of thyroid dysfunction is thyroid-related autoimmunity (TAI), characterized by a significantly higher serum level of thyroid-stimulating hormone (TSH) compared to that of women without thyroid autoimmunity. TAI is associated with a significantly increased risk of miscarriage, and the incidence of TAI in women experiencing RM is higher compared to normal fertile women. In the present study, we have performed a retrospective analysis comparing the ability to conceive, the number of miscarriages and full-term pregnancies between 227 euthyroid women with autoimmune thyroid disease affected by RM and treated with levothyroxine (LT4) as adjuvant therapy, and a control group of 230 untreated women. We have observed a significant improvement of full-term pregnancies in treated women (59%) compared to untreated women (13%, p < 0.0001). Compared to the control group, treated women had a lower percentage of miscarriages (12% vs. 30%) and improved capacity to conceive (57% vs. 29%). Using age as a variable, the outcome in women younger than 35 years was not influenced by the LT4 therapy. Whereas, in women over 35 years, supplementation with LT4 significantly reduced the miscarriage rate (p < 0.05). We can conclude that a transient impairment of TH availability, not easily detectable before pregnancy, could be an important cause of RM in a subset of euthyroid women with autoimmune thyroid disease. This transient impairment may be reverted using adjuvant treatment with low doses of LT4.

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice

Background Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice. Methods The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33−/−) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infected mice. Results Worms from IL-33−/− and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33−/− and WT mice differed only slightly. At 6 wpi, IL-33−/− mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33−/− and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues. Conclusions Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice

Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, the morphology of worms and the number of eggs in intestinal tissues were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of infected and non-infected mice.Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The number of eggs in intestinal tissues did not differ much between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Otherwise there was no difference between IL-33-/- and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues.Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.

Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation, egg excretion, and the maintenance of egg-induced pathology in intestines of mice

Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be eliminated in the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, worm morphology, reproduction, and egg excretion were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of non- and infected mice.Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The worms' reproduction, expressed as eggs per worm pair, as well as the excretion of eggs, expressed as the number of eggs in intestinal tissues, did not differ between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Besides, there was no difference between IL-33-/- and WT mice in the levels of IL-25 and TSLP in intestinal tissues.Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation, reproduction, and egg excretion. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally induced type 2 immunity in intestinal tissues in schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.

5 Differentiating transient epileptic amnesia from epilepsy in dementia and mild cognitive impairment

Objectives/AimsPatients with TEA experience epileptic seizures characterised primarily by a transient impairment of memory. These seizures sometimes include brief periods of unresponsiveness and other ictal features, including olfactory hallucinations and motor automatisms. TEA patients also report interictal memory difficulties: autobiographical amnesia, accelerated long-term forgetting, and topographical amnesia. Epileptic seizures in dementia can lead to behavioural arrest and altered responsiveness, as well as periods of increased confusion and amnesia.We aimed to compare and contrast these conditions with the objective of developing a decision aid to distinguish them efficiently in typical clinical settings.MethodsThis retrospective study examined the case notes of two groups of patients enrolled in two separate studies. The Impairment of Memory in Epilepsy (TIME) study has established a cohort of 115 patients with TEA. The Presentation of Epileptic Seizures in Dementia (PrESIDe) study assessed 144 patients with MCI or dementia and identified a clinical suspicion of epilepsy in 37 (25.7%). The Addenbrooke’s Cognitive Examination - Version III (ACE-III) scores were compared as a measure of cognitive function. The prevalence of several key seizures features in both the TEA and epilepsy in dementia populations were identified.ResultsThe average age of seizure onset in the dementia group was 76.91 years, 15 years older than in the TEA group. A range of seizure features were seen in both groups. PrESIDe patients were more likely to have seizures where loss of awareness was a feature. Automatisms occurred in a similar prevalence across both groups, although olfactory hallucinations were significantly more common in the TEA group, as were seizures where amnesia was the sole manifestation. More than 50% of participants in both groups experienced amnestic episodes on waking. Patients with epilepsy in dementia scored significantly lower than patients with TEA on all domains of the ACE-III. However, despite typically normal results on the ACE-III, patients with TEA demonstrate impairments when recall is tested over longer delays (>24 hrs), or on measures of autobiographical memory.ConclusionsIn patients with TEA, the onset of seizures occurs at a younger age than in patients who experience seizures as a feature of their dementia, there are also key differences in the types of seizure reported by these two groups of patients. In contrast to patients with dementia, those with TEA commonly perform normally on standard cognitive tests.