Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
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Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights
Belimumab (Benlysta, HGSI, GSK) is the first new drug approved by the FDA during the last 50 years to treat Lupus or SLE. The EU expert panel has recommended its approval by the EMA. The EMA gave the MAA approval last friday.
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Belimumab (Benlysta, HGSI, GSK) Lupus Review - Krishan Maggon

Belimumab (Benlysta, HGSI, GSK) Lupus Review - Krishan Maggon | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
No new drug has been approved to treat Lupus during the past 50 years. Belimumab is one of the rare new biologics to complete Phase III trials with positive outcome. It has now been approved both in the US and EU.
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Gilbert C FAURE's comment, December 14, 2013 3:14 AM
nice ti illustrate with LBT
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Cutting Edge: Intracellular IFN-β and Distinct Type I IFN Expression Patterns in Circulating Systemic Lupus Erythematosus B Cells

Cutting Edge: Intracellular IFN-β and Distinct Type I IFN Expression Patterns in Circulating Systemic Lupus Erythematosus B Cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN–stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-β.
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Implementation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Documentation in Systemic Lupus Erythematosus (SLE) Patients at an Academic Medical Center

Implementation of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Documentation in Systemic Lupus Erythematosus (SLE) Patients at an Academic Medical Center | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Background/Purpose: The 2008 European League Against Rheumatism (EULAR) Task Force on SLE management encourages the use of at least one of the SLE disease indices for the monitoring of disease activity.
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Histamine receptor 2 modifies dendritic cell responses to microbial ligands

Histamine receptor 2 modifies dendritic cell responses to microbial ligands | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The induction of tolerance and protective immunity to microbes is significantly influenced
by host- and microbiota-derived metabolites, such as histamine.
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Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus

Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The role of extrafollicular B cells in human systemic lupus is unknown. Jenks et al.
define the main components of this pathway and its prominence in severe disease. Its activation is mediated by hyper-responsiveness to Toll-like receptor-7 and leads to the generation of autoreactive...
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Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients

Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Approximately 30% of psoriasis patients develop psoriatic arthritis (PsA) and early diagnosis is crucial for the management of PsA. Here, Patrick et al. develop a computational pipeline involving statistical and machine-learning methods that can assess the risk of progression to PsA based on...
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Electron microscopy of iPSC-CM mitochondria. (A) Note a | Open-i

Electron microscopy of iPSC-CM mitochondria. (A) Note a | Open-i | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Electron microscopy of iPSC-CM mitochondria. (A) Note a long mitochondrion (yellow outlined; 6 μm).(B) Small dense structures (arrows) connect sarcoplasmic re...
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The cysteinyl leukotriene 3 receptor regulates expansion of IL-25–producing airway brush cells leading to type 2 inflammation

The cysteinyl leukotriene 3 receptor regulates expansion of IL-25–producing airway brush cells leading to type 2 inflammation | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Inhaled environmental allergens elicit type 2 lung inflammation leading to an increase in the risk of developing allergies and asthma. Bankova et al . found that one step along this pathway depends on the lipid mediator leukotriene E4 signaling through a receptor on respiratory epithelial cells to increase the number of brush cells, a rare population of chemosensory cells in the lung epithelium that express receptors shared by taste bud cells. These brush cells were identified as the major pulmonary source for synthesis of interleukin-25 (IL-25), a proinflammatory protein increased in diseases associated with type 2 inflammation. These results highlight the contributions that leukotriene E4 and IL-25 make to the signaling pathways that perpetuate allergic diseases.

Respiratory epithelial cells (EpCs) orchestrate airway mucosal inflammation in response to diverse environmental stimuli, but how distinct EpC programs are regulated remains poorly understood. Here, we report that inhalation of aeroallergens leads to expansion of airway brush cells (BrCs), specialized chemosensory EpCs and the dominant epithelial source of interleukin-25 (IL-25). BrC expansion was attenuated in mice lacking either LTC4 synthase, the biosynthetic enzyme required for cysteinyl leukotriene (CysLT) generation, or the EpC receptor for leukotriene E4 (LTE4), CysLT3R. LTE4 inhalation was sufficient to elicit CysLT3R-dependent BrC expansion in the murine airway through an IL-25–dependent but STAT6-independent signaling pathway. Last, blockade of IL-25 attenuated both aeroallergen and LTE4-elicited CysLT3R-dependent type 2 lung inflammation. These results demonstrate that CysLT3R senses the endogenously generated lipid ligand LTE4 and regulates airway BrC number and function.
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Put to sleep by immune cells

Put to sleep by immune cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The sleep disorder narcolepsy is linked to immune-system genes and is caused by the loss of neurons that express the protein hypocretin. Hypocretin-targeting immune cells have now been found in people with narcolepsy.
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Issue: Cell Stem Cell

Copyright © 2018 Elsevier Inc. except certain content provided by third parties
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Serious Infections in Rheumatoid Arthritis Offspring Exposed to Tumor Necrosis Factor Inhibitors - Vinet - 2018 - Arthritis & Rheumatology - Wiley Online Library

Abstract Objective To evaluate the risk of serious infections in rheumatoid arthritis (RA) offspring exposed to tumor necrosis factor inhibitors (TNFi) in the gestational period compared to unexposed RA offspring, as well as to children from the general population. Methods We used US claim data (2011–2015) to identify 2,989 offspring born to women who have RA and a randomly selected group of 14,596 control children, matched ≥4:1 for maternal age, year of delivery, and state of residence. We defined TNFi exposure based on ≥1 filled prescription during pregnancy. We ascertained serious infections based on ≥1 hospitalization, with infection as a primary diagnosis, at ≤12 months of life. We performed multivariable analyses, adjusting for maternal demographics, comorbidities, pregnancy complications, and drugs. Results Among RA offspring, 380 (12.7%) were exposed to TNFi during pregnancy. The percentage of serious infections in RA offspring with no TNFi exposure (2.0%; 95% confidence interval [95% CI] 1.5, 2.6) was similar to that in non‐RA offspring (1.9%; 95% CI 1.9, 2.2), while the percentage of serious infections in RA offspring with TNFi exposure was 3.2% (95% CI 1.5, 5.6). In multivariable analyses, we were unable to establish an increased risk of serious infections in RA offspring exposed to TNFi versus both non‐RA offspring (odds ratio [OR] 1.7, 95% CI 0.8, 3.7) and RA offspring unexposed to TNFi (OR 1.4, 95% CI 0.7, 2.8). Conclusion We did not demonstrate a marked excess risk for serious infections in RA offspring exposed to TNFi during pregnancy versus unexposed RA offspring or general population controls. In North America, infections are the leading cause of mortality in children age <5 years, accounting for >30% of deaths 1. Tumor necrosis factor inhibitors (TNFi) are important drugs in the treatment of rheumatoid arthritis (RA), being used in one‐third of patients 2. Since animal studies did not show fetal risk, TNFi have been commonly and increasingly used during pregnancy, now prescribed in 20% of RA pregnancies, representing a 3‐fold increase over the past 10 years 2. Despite existing concerns that these potent drugs may cause immunosuppression, there are limited data on the risk of serious infection in exposed offspring. During pregnancy, there is active transplacental transport of maternal circulating immunoglobulins (IgG) through their Fc portion 3. TNFi are all monoclonal IgG with an Fc part, except for etanercept and certolizumab, which are, respectively, a fusion protein with an Fc portion and a PEGylated Fab fragment without an Fc component 4, 5. Thus, most TNFi are actively transported across the placenta, with some reaching higher fetal than maternal blood levels. For instance, infliximab and adalimumab have the highest transplacental transfer (reaching cord blood median levels at, respectively, 160% and 150% of maternal blood levels), while etanercept and certolizumab display the lowest passage (cord blood median levels at, respectively, 4–7% and <0.25% of maternal blood levels) (4-8). As fetuses could be exposed to therapeutic (and potentially supratherapeutic) TNFi doses, there are concerns that they could cause immunosuppression in the offspring. These concerns were initially raised following the case report in 2010 of a mother with Crohn's disease receiving infliximab throughout pregnancy 9. After an uncomplicated delivery, her healthy infant received a BCG vaccine at 3 months of age and died of disseminated tuberculosis (TB). Due to the potential for immunosuppression in exposed offspring and because of the TNFi differential half‐life and transplacental transfer, the European League Against Rheumatism recommends discontinuing infliximab and adalimumab before 20 weeks of gestation and etanercept before 31–32 weeks to minimize the risk of infections in offspring, while they state that certolizumab can be continued throughout pregnancy 10. The British Society of Rheumatology guidelines for use of drugs during pregnancy also state that certolizumab is compatible with all 3 trimesters of pregnancy, but differ slightly in recommending that infliximab be discontinued before 16 weeks, and that etanercept and adalimumab be stopped before the end of the second trimester (8). Until now, there has been no reported study on the risk of infection in RA offspring exposed in utero to TNFi versus unexposed offspring. Therefore, we aimed to evaluate serious infections in RA offspring exposed to TNFi in the preconception and/or gestational period compared to unexposed RA offspring, as well as to children from the general population. Patients And Methods Data source and study population. We assembled the Pregnancies in RA Mothers and Outcomes in Offspring in the United States (PAROUS) cohort, a population‐based cohort of children born to women who have RA and a matched control group of children born to unaffected mothers, using MarketScan commercial databases (January 1, 2011 to December 30, 2015). The MarketScan commercial database is a large prospective US database of >230 million subjects with employer‐provided health insurance 11. It contains data on hospitalizations, outpatient visits, and drug prescription claims. To create the PAROUS cohort, we identified women ages 15–45 years as RA subjects (using the International Classification of Diseases, Ninth and/or Tenth Revisions [ICD‐9/10] code 714/M05) if they had any of the following: 1) ≥1 hospitalization with a diagnosis of RA at or prior to delivery, or 2) ≥2 physician visits with a diagnosis of RA, the first occurring at any time prior to the delivery and the second at any point during the study period. This RA case definition demonstrated a high sensitivity (83%) and excellent specificity (99%) when using physician diagnosis as a reference 12. A group of women without RA was randomly selected and matched ≥4:1 for age, year of delivery, and geographic location (i.e., state, division, and region) of the primary beneficiary's residence. Only women continuously enrolled within MarketScan with medical and pharmacy coverage for ≥12 months prior to delivery were included in PAROUS. We then identified the children born live to RA and unexposed women, linking mothers with their infants deterministically using family identifiers and delivery dates corresponding to birth year. Children were followed up from birth until 12 months of age, first event of interest (i.e., serious infection), end of commercial insurance eligibility, death, or end of study period (December 30, 2015), whichever came first. Delivery was defined using any inpatient hospital admission record including a pregnancy‐related diagnosis or procedure code for vaginal or caesarean delivery identified by the relevant ICD‐9/10 codes and/or procedure codes (see Supplementary Table 1, available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.40536/abstract). We excluded deliveries with diagnostic and/or procedure codes related to a molar pregnancy, spontaneous abortion or termination, and ectopic pregnancy. Exposure. We defined TNFi exposure based on ≥1 filled prescription for adalimumab, certolizumab, etanercept, golimumab, infliximab, and/or ≥1 infusion procedure claim for golimumab and/or infliximab during the preconception and/or gestational periods. We identified the date of the last menstrual period (i.e., onset of gestational period) based on the delivery date after applying a validated algorithm to term and preterm deliveries separately 13. We further categorized TNFi exposure according to the timing of the filled prescription or the infusion procedure date in relation to the gestational period. The main exposure categories were as follows: 1) RA offspring with TNFi exposure at any time during pregnancy (i.e., any prescription filled or infusion procedure claim during the gestational period), 2) RA offspring with TNFi exposure in the last 12 weeks of pregnancy (i.e., any prescription filled or infusion procedure claim within 12 weeks of delivery), 3) RA offspring with TNFi in the preconception period only (i.e., at least 1 prescription filled or infusion procedure claim in the 12 weeks preceding the gestational period, but none within the gestational period), 4) RA offspring without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the gestational period and the 12 weeks preceding it), and 5) children born to non‐RA mothers without TNFi exposure (i.e., no prescription filled or infusion procedure claim within the preconception and gestational periods). Outcome measure. The outcome of interest was serious infection occurring in the offspring. We ascertained serious infections in the offspring based on ≥1 hospitalization with infection within the first 12 months of life, with a relevant diagnostic code, as primary reason for admission (i.e., hospitalization where the primary diagnosis was an infection, including ICD‐9/10 coding by organism and/or organ involvement). This approach of identifying serious infections has been shown to have a high sensitivity (80%) and specificity (84%) when using chart review as a reference 14. We only considered the first event if >1 event was identified. Assessment of covariates. We assessed the following maternal comorbidity and pregnancy complications based on at least 1 physician billing and/or hospitalization with relevant diagnostic codes: pregestational diabetes mellitus, gestational diabetes mellitus, and preterm birth. We also identified in utero drug exposures to systemic corticosteroids, nonbiologic disease‐modifying antirheumatic drugs (DMARDs) (i.e., hydroxychloroquine, sulfasalazine, methotrexate, and leflunomide), and biologic DMARDs other than TNFi (i.e., rituximab, abatacept, and tocilizumab), based on at least 1 prescription filled and/or perfusion procedure claim by the mother during the gestational period. Statistical analysis. We used descriptive statistics to characterize the different exposure groups and calculated crude measures of risk (i.e., proportions and incidence rates) with 95% confidence intervals (95% CIs). As mean follow‐up time for offspring was very similar across exposure groups (ranging from 285 to 296 days), we performed univariable and multivariable analyses using a generalized estimating equation (GEE) method to estimate the odds ratio (OR) for the outcome of interest (i.e., serious infections), for children born to women with RA with different TNFi exposures, relative to RA offspring unexposed to TNFi, as well as to unexposed children from unaffected mothers. The GEE method accounts for correlation between observations, which might arise from including >1 offspring from the same mother. In addition, we assessed the robustness of our effect estimates by conducting exploratory univariable and multivariable Cox proportional hazards analyses, which provided very similar results. In our multivariable analyses, we adjusted for maternal age, pregestational diabetes mellitus, gestational diabetes mellitus, preterm birth, and medications (i.e., corticosteroids and nonbiologic and biologic DMARDs). All analyses were performed using SAS, version 9.4. Patient involvement. Patient advocates from the Canadian Arthritis Patient Alliance (CAPA) were involved in setting the research question, developing the study protocol, and interpreting the study findings. We plan to disseminate the results of the research to relevant patient communities (e.g., CAPA, the Arthritis Society, the Arthritis Foundation, CreakyJoints, and the ArthritisPower patient registry). Results We identified 2,989 RA offspring and 14,596 matched offspring unexposed to maternal RA (see the patient selection flow chart, Supplementary Figure 1, available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.40536/abstract). Among RA offspring, 380 (12.7%) were exposed to TNFi during pregnancy, 133 (4.4%) were unexposed during pregnancy but exposed in the preconception period, and 2,476 (82.8%) were unexposed during both the pregnancy and preconception periods. Mean maternal age was similar across all RA groups and non‐RA mothers (Table 1). Characteristic RA and TNFi pregnancy (n = 380) RA and TNFi preconception (n = 133) RA and no TNFi (n = 2,476) Non‐RA (n = 14,596) Maternal age, mean ± SD years 32.6 ± 4.1 32.0 ± 4.4 32.5 ± 4.4 32.4 ± 4.9 Maternal comorbidities, no. (%) Preexisting hypertension 58 (15.3) 17 (12.8) 387 (15.6) 1,409 (9.7) Preexisting diabetes mellitus 26 (6.8) 8 (6.0) 208 (8.4) 754 (5.2) Asthma 21 (5.5) 11 (8.3) 201 (8.1) 665 (4.6) In utero drug exposures, no. (%) Corticosteroids 213 (56.1) 62 (46.6) 667 (26.9) 285 (2.0) Nonbiologic DMARDs 74 (19.5) 23 (17.3) 379 (15.3) 9 (0.1) Other biologic DMARDs 2 (0.5) 0 (0.0) 31 (1.3) 0 (0.0) Obstetric outcomes, no. (%) Gestational diabetes mellitus 82 (21.6) 26 (19.6) 483 (19.5) 2,384 (16.3) Multiple birth 17 (4.5) 2 (1.5) 81 (3.3) 479 (3.3) Preterm birth 45 (11.8) 20 (15.0) 273 (11.0) 1,313 (9.0) a PAROUS = Pregnancies in RA Mothers and Outcomes in Offspring in the United States; RA = rheumatoid arthritis; TNFi = tumor necrosis factor inhibitors; DMARDs = disease‐modifying antirheumatic drugs. Among mothers with RA a higher proportion had pregestational diabetes mellitus and a higher proportion experienced pregnancy complications, such as preterm births and gestational diabetes mellitus (Table 1), compared to unaffected mothers. In addition, in utero drug exposures to corticosteroids and nonbiologic DMARDs were more frequent in RA offspring compared to offspring of non‐RA mothers. Over the first year of life, the percentage of serious infections in RA offspring with no TNFi exposure (2.0%; 95% CI 1.5, 2.6) was almost identical to that in non‐RA offspring (1.9%; 95% CI 1.7, 2.2), while the percentage of serious infections in RA offspring with TNFi exposure was 3.2% (95% CI 1.5, 5.6). With regard to TNFi exposure in the third trimester, the percentage of serious infections was 3.2% (95% CI 1.2, 7.7), while for TNFi exposure in the preconception period only, it was 1.5% (95% CI 0.3, 5.9) (Table 2). Exposure categories Serious infection events, no. Person‐years Serious infections, % (95% CI) Incidence rate per 100 person‐years (95% CI) Non‐RA (n = 14,596) 279 11,592 1.9 (1.7, 2.2) 2.4 (2.1, 2.7) RA and no TNFi (n = 2,476) 49 1,977 2.0 (1.5, 2.6) 2.5 (1.9, 3.3) RA and TNFi preconception (n = 133) 2 106 1.5 (0.3, 5.9) 1.9 (0.5, 7.6) RA and TNFi pregnancy (n = 380) 12 287 3.2 (1.5, 5.6) 4.2 (2.4, 7.4) RA and TNFi third trimester (n = 156) 5 118 3.2 (1.2, 7.7) 4.2 (1.8, 10.2) a PAROUS = Pregnancies in RA Mothers and Outcomes in Offspring in the United States; 95% CI = 95% confidence interval; RA = rheumatoid arthritis; TNFi = tumor necrosis factor inhibitors. In multivariable analyses, we did not find an increased risk of serious infections in RA offspring exposed to TNFi versus non‐RA offspring (OR for TNFi pregnancy 1.7 [95% CI 0.8, 3.7], OR for TNFi preconception 0.9 [95% CI 0.2, 3.9]) (Table 3 and Figure 1). The OR estimates for serious infections in RA offspring exposed to TNFi during pregnancy versus unexposed RA offspring were fairly wide and precluded a definitive conclusion (OR 1.4, 95% CI 0.7, 2.8), as were the results when we restricted TNFi exposure to the third trimester versus unexposed RA offspring (OR 1.4, 95% CI 0.5, 3.6). Comparison Unadjusted OR (95% CI) Adjusted OR (95% CI) TNFi pregnancy vs. non‐RA offspring 1.7 (0.9, 3.0) 1.7 (0.8, 3.7) TNFi preconception vs. non‐RA offspring 0.8 (0.2, 3.2) 0.9 (0.2, 3.9) TNFi pregnancy vs. unexposed RA offspring 1.6 (0.9, 3.1) 1.4 (0.7, 2.8) TNFi third trimester vs. unexposed RA offspring 1.6 (0.6, 4.2) 1.4 (0.5, 3.6) a ORs = odds ratios; PAROUS = Pregnancies in RA Mothers and Outcomes in Offspring in the United States; 95% CI = 95% confidence interval; TNFi = tumor necrosis factor inhibitors; RA = rheumatoid arthritis. When we looked at the percentage of serious infections in RA offspring exposed to specific TNFi (Table 4), we observed a trend toward more serious infections in RA offspring exposed to infliximab as opposed to those exposed to other TNFi (absolute risk difference 5.4%; 95% CI −1.1, 20.4). However, the 95% CIs for all the estimates were overlapping and, particularly in the case of golimumab and certolizumab, very imprecise. TNFi Serious infections, % (95% CI) Adalimumab (n = 108) 1.9 (0.3, 7.2) Certolizumab (n = 19) 0.0 (0.0, 20.9) Etanercept (n = 195) 3.6 (1.6, 7.6) Golimumab (n = 10) 0.0 (0.0, 34.5) Infliximab (n = 37) 8.1 (2.1, 23.0) a TNFi = tumor necrosis factor inhibitor; RA = rheumatoid arthritis; 95% CI = 95% confidence interval. We evaluated the risk of serious infections in RA offspring exposed to infliximab as opposed to other TNFi in an exploratory multivariable analysis, adjusting for maternal age and in utero corticosteroid exposure (but unable to control for preterm birth and gestational diabetes mellitus since no case occurred for these covariates). Again, there was a trend for an increased risk of serious infections in RA offspring exposed to infliximab during pregnancy versus RA offspring exposed to other TNFi, although the 95% CI included the possibility of no difference (OR 3.0, 95% CI 0.7, 11.8). The most frequent type of serious infections in RA offspring exposed to TNFi, unexposed RA offspring, and non‐RA offspring was acute bronchiolitis due to respiratory syncytial virus, accounting for 36% (95% CI 14, 64), 31% (95% CI 19, 46), and 33% (95% CI 27, 38) of cases, respectively, in these 3 groups (Table 5). Among all cases of serious infection occurring in RA offspring (exposed and unexposed to TNFi), we did not identify any case of TB. Types of serious infection Cases of serious infection RA offspring exposed to TNFi in pregnancy and/or preconception (n = 14) RA offspring unexposed to TNFi (n = 49) Non‐RA offspring (n = 279) Acute bronchiolitis due to RSV 36 (14, 64) 31 (19, 46) 33 (27, 38) Acute bronchiolitis due to other organisms 36 (14, 64) 20 (11, 34) 18 (14, 23) Viral meningitis 7 (1, 31) 8 (3, 19) 4 (2, 7) Other 21 (6, 51) 41 (27, 56) 55 (49, 61) a Values are the % (95% confidence interval). TNFi = tumor necrosis factor inhibitors; RA = rheumatoid arthritis; RSV = respiratory syncytial virus. Discussion Within the largest cohort of RA offspring exposed to TNFi ever assembled, we did not detect a marked excess risk associated with overall TNFi exposure during the preconception and gestational period. In addition, we did not identify any cases of TB. We observed a trend in the risk of serious infections in RA offspring exposed to infliximab, as opposed to other TNFi, during pregnancy. In a recent study of 80 pregnant women with inflammatory bowel disease (IBD) exposed to adalimumab or infliximab, investigators assessed maternal and cord blood levels of TNFi 15. The median ratio of infant‐to‐mother drug concentration at birth was 1.21 for adalimumab (95% CI 0.94, 1.49) and 1.97 for infliximab (95% CI 1.50, 2.43). The investigators showed that the mean half‐life of infliximab and adalimumab was, respectively, 3.7 and 2.0 times longer in infants than in adult nonpregnant patients. This translated to a longer mean time to drug clearance in infants exposed in utero to infliximab as opposed to those exposed to adalimumab (respectively, 7.3 months [95% CI 6.2, 8.3] and 4.0 months [95% CI 2.9, 5.0]) 15. Of note, drug concentrations were detectable up to 12 months of age in offspring exposed to infliximab. These data suggest that the pharmacokinetic properties of TNFi (i.e., their half‐life) combined with their immunologic structure (i.e., harboring an Fc fragment or not) influence drug levels in exposed offspring and the potential risk of having a serious infection. Our study has many strengths. It is the first study to evaluate the risk of serious infections in RA offspring exposed to TNFi, using an RA group and general population unexposed group as comparators. Owing to the availability of data on maternal medical diagnoses and prescription claims preceding delivery, we were able to account for important confounding factors, such as other medications, and present adjusted effect estimates for each comparison. Another strength of our study resides in the use of a large health plan database, which allowed us to assess a rare outcome in RA offspring exposed to TNFi. In addition, we used case definitions for RA and serious infections that have been shown to be valid in prior studies 12, 14. Moreover, our data source (i.e., MarketScan) has been extensively used for the conduct of pharmacoepidemiologic studies in rheumatic diseases, particularly related to biologic DMARDs (such as TNFi) and RA outcomes 16-19. Furthermore, administrative database studies like ours are less prone to selection bias or recall bias compared to drug or pregnancy registries, which might differentially select drug‐exposed subjects based on certain characteristics and/or outcomes or collect exposure information after the outcome has occurred 20. We must acknowledge some potential limitations, particularly TNFi exposure misclassification. Exposure to TNFi was defined based on filled prescriptions, except for infliximab and golimumab exposures, which were also identified by infusion procedure codes. There might be some concerns that filled prescriptions may not have reflected actual use. However, it is likely that most women who filled a prescription for TNFi took at least 1 dose, because within the MarketScan commercial database the vast majority of subjects have out‐of‐pocket costs associated with prescriptions filled 21. Thus, we believe this would not have invalidated our findings. As MarketScan (like most administrative databases) does not provide information on the gestational age at birth and/or the last menstrual period, we estimated the gestational period by applying a validated algorithm to term and preterm deliveries separately 13. Thus, misclassification of TNFi during the gestational period is possible. However, since our sensitivity analysis restricted to RA offspring exposed to TNFi in the 12 weeks prior to delivery showed a similar effect estimate to the one obtained in our primary analysis, we do not think that misclassification explains all of our study findings. Since MarketScan does not explicitly record RA activity measures, our study might be subject to residual confounding by this factor. However, we adjusted for important drug exposures, such as the use of steroids and nonbiologic DMARDs, which might be associated with high disease activity. Thus, by accounting for medication exposures, this might have at least partially controlled for disease activity. To date, there have been limited data on the risk of serious infections in children born to mothers with inflammatory conditions such as IBD and exposed in utero to TNFi. Mahadevan et al have reported findings from the Pregnancy in Inflammatory Bowel Diseases And Neonatal Outcomes (PIANO) registry, a US prospective cohort of pregnant women with IBD and their offspring followed up until 12 months after delivery 22. PIANO includes 102 offspring exposed to TNFi monotherapy, 59 offspring exposed to combination therapy with TNFi and thiopurines, as well as an unexposed group of 265 children. The authors reported an increased risk of infections at 12 months of age in offspring exposed to combination therapy with TNFi and thiopurines relative to the unexposed group (relative risk [RR] 1.50, 95% CI 1.08, 2.09). However, they did not report a specific effect estimate for the risk of infections in children exposed to TNFi monotherapy (compared to unexposed offspring). In addition, the study results have only been reported in abstract form so far. In the study mentioned above that evaluated 80 IBD offspring exposed in utero to adalimumab or infliximab, Julsgaard et al assessed the risk of infections in the first year of life, as reported by the mothers 15. The investigators did not observe an increased risk of infections in children exposed to TNFi monotherapy after the thirtieth gestational week compared to those who were only exposed before the thirtieth gestational week (RR 0.54, 95% CI 0.26, 1.16). However, offspring exposed to both TNFi and thiopurines had a ≥2‐fold increase in the risk of infections compared to those only exposed to TNFi (RR 2.7, 95% CI 1.09, 6.78). These study findings and the preliminary results from the PIANO registry suggest that TNFi are associated with a potential increase in the risk of infections in IBD offspring when used in combination with thiopurines during pregnancy. In summary, we did not observe a marked excess risk for serious infections in RA offspring exposed to TNFi during pregnancy, including the third trimester, versus unexposed RA offspring and children from the general population. However, we cannot exclude a differential risk according to specific TNFi, with infliximab potentially resulting in a 3‐fold increase in the risk of serious infections compared to other TNFi. More studies are needed to further evaluate whether the risk of serious infections in exposed offspring is influenced by individual TNFi characteristics. Author Contributions All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. Dr. Vinet had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study conception and design Vinet, De Moura, Curtis, Bernatsky. Acquisition of data Vinet, Abrahamowicz, Curtis, Bernatsky. Analysis and interpretation of data Vinet, De Moura, Pineau, Abrahamowicz, Curtis, Bernatsky. Supporting Information References
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Aurinia Pharmaceuticals: Clear Winner In Lupus Nephritis - Aurinia Pharma (NASDAQ:AUPH)

Aurinia Pharmaceuticals: Clear Winner In Lupus Nephritis - Aurinia Pharma (NASDAQ:AUPH) | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Aurinia’s voclosporin has done very well in earlier trials. Currently, it is running a phase 3 trial with data due next year.The company looks like a good inve...
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Rheumatoid Arthritis - Knee | Blausen Medical

Rheumatoid Arthritis - Knee | Blausen Medical | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
The skeletal system provides the framework for the body and protects the internal organs. Joints exist where two bones meet to allow movement and flex...
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Therapeutic Potential of Mesenchymal Cell–Derived miRNA-150-5p–Expressing Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF

Therapeutic Potential of Mesenchymal Cell–Derived miRNA-150-5p–Expressing Exosomes in Rheumatoid Arthritis Mediated by the Modulation of MMP14 and VEGF | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial tissue inflammation and joint destruction associated with the activation of angiogenesis. Exosomes, which play a role in cell-to-cell communication as carriers of genetic information, transfer microRNAs (miRNAs or...
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Regulatory T cells in the treatment of disease

Regulatory T cells in the treatment of disease | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Abstract
Regulatory T (Treg) cells suppress inflammation and regulate immune system activity. In patients with systemic or organ-specific autoimmune diseases or those receiving transplanted organs, Treg cells are compromised. Approaches to strengthen Treg cell function, either by expanding them ex vivo and reinfusing them or by increasing the number or capacity of existing Treg cells, have entered clinical trials. Unlike the situation in autoimmunity, in patients with cancer, Treg cells limit the antitumour immune response and promote angiogenesis and tumour growth. Their immunosuppressive function may, in part, explain the failure of many immunotherapies in cancer. Strategies to reduce the function and/or number of Treg cells specifically in tumour sites are being investigated to promote antitumour immunity and regression. Here, we describe the current progress in modulating Treg cells in autoimmune disorders, transplantation and cancer.
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Fatty acid metabolism driven mitochondrial bioenergetics promotes advanced developmental phenotypes in human induced pluripotent stem cell derived cardiomyocytes

Fatty acid metabolism driven mitochondrial bioenergetics promotes advanced developmental phenotypes in human induced pluripotent stem cell derived cardiomyocytes | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Preferential utilization of fatty acids for ATP production represents an advanced
metabolic phenotype in developing cardiomyocytes. We investigated whether this phenotype could be attained in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and assessed its influence on...
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Targeting the Extracellular Signal-Regulated Kinase 5 Pathway to Suppress Human Chronic Myeloid Leukemia Stem Cells

Targeting the Extracellular Signal-Regulated Kinase 5 Pathway to Suppress Human Chronic Myeloid Leukemia Stem Cells | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Highlights

ERK5 is constitutively active in chronic myeloid leukemia (CML) cells

ERK5 pathway inhibition reduces the growth of CML cells in vitro and in vivo

ERK5 pathway inhibition strikingly reduces CML progenitor/stem cell maintenance

The combination of ERK5i with imatinib reduces the expression of stem cell proteins
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Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer
et al. investigate the gut microbiome’s role in pediatric UC treated with two conventional
therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including...
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Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation

Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
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Professional illustration by Patrick Lane, ScEYEnce Studios.[1]: pending:yes...
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Stem Cells Principal Topic for Doorstep Meeting and Keynote Lecture

Stem Cells Principal Topic for Doorstep Meeting and Keynote Lecture | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Both the day-long 2018 ASCB Doorstep Meeting on Saturday, December 8, and the Keynote Lecture that evening for the 2018 ASCB|EMBO Meeting will feature discussions of stem cells. In fact, this year’s Keynote speaker helped plan the lineup of presenters for the Doorstep Meeting.
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As stem cell and gene technologies advance, La Jolla conference mushrooms

As stem cell and gene technologies advance, La Jolla conference mushrooms | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
In 2006, a few hundred mostly local researchers gathered in La Jolla to discuss the emerging but still science-fictiony field of stem cells.
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Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells

Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are
a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional...
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Stem cells control their own fate, making lab-grown tissues less effective | Imperial News | Imperial College London

SIGNAL FAILURE - Tissues grown in the lab from stem cells may fail to live up their therapeutic promise because the cells choose their own fate.
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Dietary essential oil protects gastrointestinal tract against 1,2-dimethylhydrazine and dextran sodium sulfate induced ulcerative colitis associated colon carcinogenesis | Abstract

Dietary essential oil protects gastrointestinal tract against 1,2-dimethylhydrazine and dextran sodium sulfate induced ulcerative colitis associated colon carcinogenesis | Abstract | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Colorectal cancer (CRC) is the third common malignancy and a major cause of morbidity and cancer-related death worldwide. Carvacrol is a dietary essen..
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Stem Cells in Blood Vessels Could Repair Damage After Heart Attack

Stem Cells in Blood Vessels Could Repair Damage After Heart Attack | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Heart attacks kill heart tissue. Could the stem cells in that live in blood vessels be directed to repair damage after heart attack?
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Tissue-Specific RNA Carriers Give Cell-Level Delivery Confirmation

Tissue-Specific RNA Carriers Give Cell-Level Delivery Confirmation | Autoimmune diseases (Lupus, RA), Vaccines and Stem Cell Therapies Highlights | Scoop.it
Nanoparticle delivery of functional nucleic acids to specific tissues can be quickly confirmed at the cellular level with a new screening technique.
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