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Abstract Background Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population. Methods A case-control and a familial study were performed. Positions -1082, -819 and -592 of the IL-10 promoter were typed by TaqMan and allele specific PCR. IL10R and IL10G microsatellites were amplified with labelled primers, and they were subsequently run on an automatic sequencer. In this study 446 patients and 573 controls were included, all of them white Spaniards. Extended haplotypes encompassing microsatellites and SNPs were obtained in families and estimated in controls by the Expectation-Maximization algorithm. Results No significant associations after Bonferroni correction were observed in the SNPs or any of the microsatellites. Stratification by HLA-DQ2 (DQA1*0501-DQB1*02) status did not alter the results. When extended haplotypes were analyzed, no differences were apparent either. Conclusion The IL-10 polymorphisms studied are not associated with celiac disease. Our data suggest that the IL-10 alteration seen in patients may be more consequence than cause of the disease.

Research Question: Despite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction., Design: A retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes., Results: 79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes., Conclusion: The use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : A healthy pregnancy begins with an adequate endometrial state, even before the arrival of a blastocyst. Proper endometrial priming and the development of a tolerogenic decidua are key steps in creating the perfect environment for implantation and pregnancy. In these processes, the involvement of the maternal immune system seems to be of great relevance, modulating the different decidual immune populations to prepare the endometrium for a potential pregnancy. However, certain local pathologies of an inflammatory and autoimmune nature appear to have a direct impact on these phenomena, thus altering patients' reproductive outcomes. Methods : This literature review analyzes original articles, reviews, systematic reviews, and meta-analyses published between 1990 and 2024, concerning the impact of different inflammatory and autoimmune conditions on endometrial status and fertility. The included papers were obtained from Medline (Pubmed) and the Cochrane library. Results : There is evidence that endometriosis, adenomyosis, and chronic endometritis, through the promotion of a chronic inflammatory environment, are capable of altering endometrial immune populations, and, thus, processes essential for early pregnancy. Among other effects, these conditions have been linked to impaired decidualization, alterations in progesterone responsiveness, and hindered placentation. Similarly, antiphospholipid syndrome (APS), thyroid dysfunction, diabetes, and other pathologies related to glucose and gluten metabolism, due to their autoimmune nature, also appear to have a local impact on the uterine environment, affecting reproductive success through different mechanisms, including altered hormonal response and, again, impaired decidualization. Conclusions : The management of inflammatory and autoimmune diseases in assisted reproduction patients is gaining importance due to their direct impact on the endometrium. It is necessary to follow current expert recommendations and established therapeutic approaches in order to improve patients' prospects, ranging from antibiotic treatment in chronic endometritis to heparin and aspirin in APS, as well as hormonal treatments for endometriosis/adenomyosis or a gluten-free diet in celiac disease. All of them and the rest of the therapeutic perspectives, both current and under investigation, are presented throughout this work, assessing the possible improvements for reproductive outcomes.

Nowadays, recurrent pregnancy loss (RPL) is an undesirable condition suffered by many patients of reproductive age. In this scenario, certain immune cell populations and molecules, involved in maternal-fetal compatibility, have emerged as factors related with the pathogenesis of RPL. Among them, uterine Natural Killer cells (uNKs) appear to be of great relevance. These cells are involved in numerous processes during pregnancy, such as the remodeling of uterine spiral arteries or the control of trophoblast invasion. These functions are regulated by the interactions that these cells establish with the extravillous trophoblast, mainly through their Killer Immunoglobulin-like Receptors (KIRs) and the Human Leukocyte Antigen-C (HLA-C) molecules expressed by the embryo. A high level of polymorphism has been reported for both molecules involved in this interaction, with some of the possible KIR-HLA-C combinations being associated with an increased risk of RPL. However, the complexity of the maternal-fetal interface goes beyond this, as other HLA molecules also appear to be related to this reproductive pathology. In this review, we will discuss the role of uNKs in pregnancy, as well as the polymorphisms and clinical implications of KIR-HLA-C binding. We will also address the involvement of other, different HLA molecules in RPL, and the current advice on the appropriate management of patients with 'immunological mismatch', thus covering the main aspects regarding the involvement of maternal-fetal compatibility in RPL.

Objective: To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding., Design: Prospective observational cohort study., Setting: Clinic and university laboratories., Patient(s): Participants included 39 women with recurrent miscarriages who had undergone in vitro fertilization cycles with donated oocytes and 21 healthy oocyte donors with proven fertility., Intervention(s): Endometrial biopsy samples were collected from both patients and donors, and the KIR genotypes of the assisted reproductive technology patients were analyzed., Main Outcome Measure(s): Endometrial gene expression (cluster of differentiation [CD] antigens and anti-inflammatory and proinflammatory interleukins) and the number and percentage of regulatory T and NK cell populations in patients and donors were determined. Subsequently, the results obtained were categorized in the group of patients by KIR genotype. Killer cell immunoglobulin-like receptor-HLA-C binding was also examined in patients, considering their KIRs., Result(s): A higher percentage of CD56 dim CD16 + NK cells were observed in patients than those in healthy donors. Nevertheless, when categorizing patients by KIR genotype and comparing the KIR AA (35.9%), AB (43.6%), and BB (20.5%) groups, no statistically significant difference was observed in either endometrial gene expression or any of the immune cell populations analyzed. Finally, no differences in binding between KIR and HLA-C molecules were registered among these 3 sets of patients., Conclusion(s): The reported increase in the number of NK cells with a cytotoxic profile in the endometrium of women with a history of recurrent miscarriages cannot alone explain these events because no relationship is observed between such cellular increase and the KIR genotypes, which individually, and in combination with the different HLA-C alleles, have also been associated, by previous studies, with negative reproductive outcomes., Clinical Trial Registration Number: 1405-MAD-025-JG., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Nowadays, there are many efforts focused on improving embryo quality for assisted reproduction treatments. Nevertheless, there are important maternal aspects, such as decidualization, also essential for pregnancy, often forgotten. With this review, we intend to highlight the main events involved in this endometrial phenomenon, as well as the cells and molecules that have recently been related to it., Recent Findings: Decidualization entails a complete transformation of the endometrium, with recent research reaffirming progesterone as its main molecular trigger. Certain immune components and membrane molecules have also been found to play a role in it, notably the killer immunoglobulin-like receptors (KIR) of uterine natural killer (uNK) cells, as well as the human leukocyte antigen (HLA)-F., Summary: Progesterone directs the cellular changes that take place during decidualization, as well as the recruitment and maturation of uNKs, along with the coordinated action of interleukin-15. Likewise, the role of KIR and HLA-F in this process and in the subsequent development of pregnancy is being highlighted in many studies, with effects on reproductive outcomes related to the different genotypes of these molecules., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Research Question: Do patients with adenomyosis present a dysregulated endometrial receptivity that can be reversed with personalized embryo transfer (PET) by transcriptomic-based progesterone adjustment, improving IVF outcomes?, Design: A multicentre, retrospective, cohort study that transcriptomically analysed the endometrial receptivity of the endometrium in patients with adenomyosis (n = 81) and healthy women (n = 231). Subsequently, implantation, biochemical and clinical miscarriage, and live birth rates between adenomyosis patients with one previous implantation failure using donor oocytes who received (n = 59) or did not receive (n = 66) PET based on endometrial receptivity, were observed to evaluate if adjusted progesterone improves reproductive outcomes of adenomyosis patients., Results: Patients with adenomyosis significantly presented an altered endometrial receptivity (non-receptive) compared with healthy patients (53.1% versus 37.2%, P = 0.0179), elevating the risk of adenomyosis patients having a non-receptive endometrium 42.59% higher (95% CI 41.50 to 44.45). No significant differences were found in implantation (62.7% versus 78.8%, P = 0.0514), biochemical (13.5% versus 3.9%, P = 0.1223) and clinical (10.8% versus 15.4%, P = 0.7543) miscarriage, or live birth rates (75.7% versus 80.8%, P = 0.6066), in patients with PET compared with those without PET., Conclusions: Women with adenomyosis presented an altered expression of genes involved in decidualization, and a higher rate of non-receptive endometrial statuses than controls. Although progesterone is indispensable for implantation, adjusting progesterone before PET, using endometrial transcriptomic signatures, does not improve IVF outcomes in patients with adenomyosis. Other molecular mechanisms beyond progesterone regulation may be involved in implantation failure., (Copyright © 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the pregnancy, miscarriages, and live birth rates (LBRs) according to maternal killer cell immunoglobulin-like receptor (KIR) genes expressed by uterine natural killer cells and paternal or oocyte donor human leukocyte antigen-C (HLA-C) genes expressed by trophoblast cells in patients with recurrent reproductive failure., Design: Prospective observational cohort study., Setting: Private infertility center., Patient(s): Participants included 204 women with recurrent miscarriage or recurrent implantation failure., Intervention(s): The KIR and HLA-C genotypes of all women and HLA-C of their partners, gamete donors, miscarriage tissue, and babies were analyzed., Main Outcome Measure(s): All clinical variables (pregnancy, miscarriage, and LBRs) were analyzed and categorized based on KIR, oocyte origin, and single embryo transfer (SET)/double embryo transfer (DET)., Result(s): A higher miscarriage rate was observed after DETs in KIR AA mothers (47.8% egg donation and 37.5% in vitro fertilization [IVF]) compared with KIR AB (10.5% egg donation and 12.5% IVF) or KIR BB (6.7% egg donation and 0% IVF). A significantly decreased LBR was observed after DETs with oocyte donation in KIR AA patients (4.3%) compared with KIR AB (26.3%) or BB (46.7%). The LBR decreased significantly as the fetal HLA-C2 load increased in KIR AA women., Conclusion(s): Elective SET improves the reproductive outcomes compared with DET. An increased embryo HLA-C2 load has a negative impact on the LBR in KIR AA patients. The selection of HLA-C1 over HLA-C2 donors could have a positive impact on the LBR in KIR AA patients., Clinical Trial Registration Number: NCT04052438., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Problem: Which is the prevalence and seroprevalence of celiac disease (CD) in women with recurrent reproductive failure?, Method of Study: Retrospective study performed in a single infertility clinic from September 2016 to December 2017. A total of 690 women with unexplained history of recurrent miscarriage and/or recurrent implantation failure were consecutively recruited. IgA anti-transglutaminase 2 (TG2) antibody data were collected, as well as IgG anti-TG2 and IgA/IgG anti-deamidated gluten peptide (DGP) data in most cases, and IgG anti-gliadin antibodies occasionally. In selected women, HLA-DQ genotyping was requested. Biopsy was suggested to all women with positive serological results or belonging to CD risk groups. Reproductive outcomes were recorded from women with high suspicion of CD and a control group comprised of 49 women., Results: Anti-TG2-positive women comprised 1% of the sample. An additional 4% was observed considering less-specific antibodies (31 women). Only 39% of sero-positive women accepted duodenal biopsy. HLA and biopsy data discarded CD in 14 sero-positive cases (37%), only one with anti-TG2 antibodies. CD was suggested in 10 sero-positive and three sero-negative women (1.9%). Compared with controls, the live birthrate of the studied women with probable CD was significantly decreased before gluten removal of the diet (P = .015), but significantly increased after that (P = .020)., Conclusion: One percent CD prevalence should be expected after anti-TG2 serological screening. However, more sensitive approaches should be explored, especially considering the potential beneficial effect of the gluten-free diet on the reproductive outcomes of women with CD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Research Question: Granulocyte colony-stimulating factor (G-CSF) acts on reproductive function at different stages, but its effects on the early stages of embryo development are unknown. The aim of this study was to assess the effect of G-CSF administration during treatment with assisted reproductive technologies (ART) and early pregnancy on newborns., Design: Retrospective study in women undergoing egg donation, with a study group including 33 live-born children from a pregnancy in which G-CSF was administered, and a control group of 3798 children in which this medication was not ordered during pregnancy. The analysis was of perinatal outcomes resulting from G-CSF treatment administered off-label compared with a control group., Results: No significant differences were found in maternal age (40.9 ± 0.1 versus 38.9 ± 1.8, P = 0.055), body mass index (23.2 ± 0.2 versus 22.6 ± 1.5, P = 0.503), infant birthweight (2952 ± 200 versus 3145 ± 270 g, P = 0.184), gestational age (38 ± 1 versus 37 ± 1 weeks, P = 0.926) or length (50.2 ± 1.5 versus 48.7 ± 2.7 cm, P = 0.678) (between the control group and women treated with G-CSF, respectively). The prematurity rates of births before week 36 (10.0% versus 9.5%, P = 0.783) or week 32 (2.2% versus 0.0%, P = 0.585) were similar in the control and study groups, respectively. The incidence of low birthweight (<2500 g; 19.6% versus 11.8%, P = 0.570) or very low birthweight (1500 g; 2.5% versus 0.0%, P = 0.454) was not significantly different between non-treated and G-CSF-treated women, respectively., Conclusions: Administration of G-CSF at embryo transfer and during early pregnancy in recurrent miscarriage patients with KIR-HLA-C mismatch undergoing egg donation ART treatment does not convey a higher risk of perinatal complications., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

Pancreatic Autoimmunity is defined as the presence of autoantibodies and more frequent need for insulin treatment. Affected women presenting recurrent implantation failure (RIF) or recurrent miscarriage (RM) are often misdiagnosed. The objective of thestudy was to describe clinical and metabolic profiles suggestive of Pancreatic Autoimmunity and therapeutic strategy in patients with RIF/RM. We analyzed retrospectively 735 patients, and have identified a subset (N = 20) with similar metabolic characteristics. At the same time, we included a control group (n = 39), with similar demographic characteristics and negative for pancreatic, thyroid or celiac disease autoimmunity. The patients identified with autoimmune metabolic problem (N = 20) had relatives with diabetes mellitus. At 120 minutes after Oral Glucose Tolerance Test (OGTT) low level of insulin secretion (<2 IU/ml) was found in 70% of patients. Glutamic acid decarboxylase 65 (GAD 65) antibodies, with or without other autoantibodies, were positive in80% of patients and anti-IA2 alone were positive I the rest. Since pregestational period, insulin administration was recommended for 10 patients, metformin for 4 patients and exclusively diet control in 5 of them. Significantly increased live bith rates (LBR) per cycle were observed after metabolic control (52%) compared with live birth rate (LBR) after cycles without control (7.5%) (p<0.0001). We noticed 2 cases of pre-eclampsia and 6 low-birth weights. Insulin administration was needed during the pregnancy in 68% of patients and after childbirth in 31.57% of them. In our control group, all of patients (n = 39) underwent ART (53.8% SET and 46.1% DET) with a 50% (SET) and 61.9% (DET) live birth rate (LBR) per cycle. Patients with RIF/RM, normal BMI, low insulin levels after OGTT could benefit from additional metabolic immune testing. A correct diagnosis and treatment could have a positive impact on their reproductive results and live birth rate., Competing Interests: The authors have declared that no competing interests exist.

The immune system's role in recurrent reproductive failure is a controversial issue in assisted reproduction. Most studies into immune system implication in reproduction have focused on finding markers of peripheral blood and less on the uterine environment. Peripheral blood natural killer cells have become an "immune study core" for women with recurrent miscarriage or recurrent implantation failure, based on the mistaken notion that they cause reproductive failure by killing or "rejecting" the embryo. Maternal-fetal tolerance begins at the uterine level, so successful adaptation to the fetus occurs after a complicated process. Insufficient uterine lining invasion by an invading extravillous trophoblast is the primary defect in pregnancy disorders such as recurrent miscarriage. This process is regulated by the interaction between maternal killer immunoglobulin-like receptors (KIRs), expressed by uterine natural killer cells (uNK), and their ligand human leukocyte antigen (HLA) C, expressed by the extravillous trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR AA when the fetus has paternal HLA-C2. A recent report has indicated that the expression of more than one paternal HLA-C by the extravillous trophoblast in assisted reproduction may affect placentation in mothers with KIR AA. This review provides insight into the immune system's role in assisted reproductive treatments. These insights can have an impact on the selection of single-embryo transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent implantation failure and recurrent miscarriage depending on their KIR haplotype., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The immune system's role in recurrent reproductive failure is a controversial issue in assisted reproduction. New insight about maternal tolerance in assisted reproduction has been reported and could explain some of the recurrent miscarriage and/or recurrent implantation failure related causes named until now as unknown., Recent Findings: Most of the previous studies about immune system implication in reproduction were focused on finding markers on peripheral blood. Maternal tolerance begins at the uterine level, so successful adaptation to the fetus happens after a complicated process. Insufficient invasion of the uterine lining by invading extravillous trophoblast is the primary defect in pregnancy disorders such as recurrent miscarriage, and this process is regulated by interaction between maternal killer immunoglobulin-like receptors (KIRs) expressed by the uterine natural killer cells and their ligand human leukocyte antigen (HLA)-C expressed by extravillous trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR AA when the fetus has paternal HLA-C2. Recently, it has been reported that the expression of more than one paternal HLA-C by extravillous trophoblast in assisted reproduction may affect placentation in mothers with KIR AA., Summary: The review provides insight about the immune tolerance process. These insights could have an impact on the selection of single embryo transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent miscarriage or recurrent implantation failure and a KIR AA haplotype.

Problem: Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT-like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells)., Method of Study: Observational study of RRF women with NK or NKT-like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation., Results: By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001)., Conclusions: Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: Natural killer (NK, CD3(-)CD56(+)/CD16(+)) and NKT-like cells (CD3(+)CD56(+)/CD16(+)) activity is considered among the key factors for reproductive success. In the absence of immunological screening, beneficial effects of intravenous immunoglobulin (IVIG) in preventing recurrent reproductive failure (RRF) have not been reported. Here, we analyse the IVIG influence on pregnancy success in women with RRF and circulating NK or/and NKT-like cells expansion., Method of Study: One hundred fifty-seven women with previous recurrent miscarriage and/or recurrent implantation failure after in vitro fertilization were consecutively studied. Sixty-four patients with CD56(+) cell expansion, no apparent underlying disease and who maintained their desire to conceive were selected. Forty of them received IVIG during pregnancy., Results: Overall, the clinical pregnancy rate for the women under IVIG therapy was 92.5% and the live birth rate was 82.5%. Significantly lower pregnancy and live birth rates (25% and 12.5%, respectively) were observed for the patients with recurrent pregnancy loss and NK/NKT-like cells expansion without IVIG. After three cycles of IVIG, NK cell percentages decreased significantly and these values persisted throughout gestation., Conclusion: Intravenous immunoglobulin therapy for women with RRF and NK or NKT-like cell expansion was a safe and beneficial therapeutic strategy that associated with high clinical pregnancy and live birth rates., (© 2012 John Wiley & Sons A/S.)

Background: Studies in primary HIV-1 infection and advanced HIV-1 disease have demonstrated that HIV-1 DNA associated with peripheral blood mononuclear cells (PBMC HIV-1 DNA) has predictive value for disease progression., Objectives: To analyse in asymptomatic HIV-1 chronic infection the predictive value of PBMC HIV-1 DNA for virological failure., Study Design: In 115 individuals who had previously participated in study STIR-2102, we retrospectively analysed the PBMC HIV-1 DNA by quantitative real-time PCR. Antiretroviral naïve patients (baseline pre-ART) received 6 weeks of ART prior to randomisation (baseline post-ART). The predictive value of PBMC HIV-1 DNA, HIV-1 RNA in plasma and CD4+ T cells, at baselines pre-ART and post-ART, was determined by Kaplan-Meier and Proportional Hazards Regression analyses., Results: At baseline post-ART, 82% of patients showed suppression of HIV-1 RNA, however they maintained significant amounts of HIV-1 DNA (geometric mean: 690 copies/10(6) PBMC). Pre-ART and post-ART levels of HIV-1 DNA and pre-ART levels of HIV-1 RNA showed predictive value (Log-Rank test: p<0.001, p<0.001, p=0.003, respectively). In a multivariate model post-ART PBMC HIV-1 DNA was the stronger predictive variable (adjusted HR, 2.51 [95% CI, 1.33-4.73, p=0.004]) independently of HIV-1 RNA (HR 1.74 [95% CI, 1.16-2.61, p=0.007])., Conclusions: PBMC HIV-1 DNA is an effective prognostic marker for virological outcome in individuals with asymptomatic HIV-1 chronic infection., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Biological therapies have revolutionized the treatment of chronic systemic diseases in which the immune system disorders form a part of the disease mechanism. In these diseases, the patients follow different drug treatments for long periods of time that causes serious adverse reactions and often obtain unsatisfactory efficacy results. Due to the research conducted in the last 10 years, biological drugs have been introduced into the treatment that are aimed against specific targets, such as inflammatory and immunopathological responses that give rise to tissue injury. The new biological therapies have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. The present work aims to provide a global and up-dated view on the biological agents used most in the usual clinical practice and their importance in the management of the chronic immunologically based inflammatory diseases.

Background: Celiac disease (CD) is a chronic disorder characterized by a pathological inflammatory response after exposure to gluten in genetically susceptible individuals. The HLA complex accounts for less than half of the genetic component of the disease, and additional genes must be implicated. Interleukin-10 (IL-10) is an important regulator of mucosal immunity, and several reports have described alterations of IL-10 levels in celiac patients. The IL-10 gene is located on chromosome 1, and its promoter carries several single nucleotide polymorphisms (SNPs) and microsatellites which have been associated to production levels. Our aim was to study the role of those polymorphisms in susceptibility to CD in our population., Methods: A case-control and a familial study were performed. Positions -1082, -819 and -592 of the IL-10 promoter were typed by TaqMan and allele specific PCR. IL10R and IL10G microsatellites were amplified with labelled primers, and they were subsequently run on an automatic sequencer. In this study 446 patients and 573 controls were included, all of them white Spaniards. Extended haplotypes encompassing microsatellites and SNPs were obtained in families and estimated in controls by the Expectation-Maximization algorithm., Results: No significant associations after Bonferroni correction were observed in the SNPs or any of the microsatellites. Stratification by HLA-DQ2 (DQA1*0501-DQB1*02) status did not alter the results. When extended haplotypes were analyzed, no differences were apparent either., Conclusion: The IL-10 polymorphisms studied are not associated with celiac disease. Our data suggest that the IL-10 alteration seen in patients may be more consequence than cause of the disease.

Escherichia coli meningitis is a frequent pathology in children younger than 3 years old, but is an uncommon disease in adults. E. coli infection is the main cause of intrahospital bacteremia as a consequence of the employment of different medical procedures. Our patient, male, 69 years old, presented with fever, progressive difficulty in breathing, and shivers 24 h after transrectal prostate biopsy, with an absence of any other symptoms. He received prophylactic treatment with ciprofloxacin and later empirical treatment with ampicillin and tobramicin. After that, the patient presented with fever, headache, behavioral changes, somnolence, disorientation, a fluctuating level of conscience, cutaneous widespread pallor, and acute urinary retention. On physical exploration, we observed generalized hypoventilation, Glasgow 10, stiffness of the neck, inconclusive Kernig; the remaining neurological exploration was normal. Systematic of blood: leukocytes = 8,510/mm3 (94.5% polymorphonuclear), platelet = 87,000/mm3, pH = 7.51, pCO2 = 28.8 mmHg, pO2 = 61 mmHg, O2 saturation = 93.8%, and remaining values were normal. Chest X- ray, cranial CT scan, urine cultures were normal. Blood culture: E. coli. CSF: glucose <0.4 g/l, total proteins = 3.05 g/l, PMN = 7 cells. Microscopic examination of the CSF: Gram-negative bacilli; CSF's culture: abundant E. coli. The case of acute meningitis by multiresistant E. coli after transrectal prostate biopsy presented demonstrates that antibiotic prevention with ciprofloxacin is not absolutely risk free. Besides the use of antibiotic prevention for multiresistant microorganisms, the urologist and other physicians involved in the procedure must not forget that the rate of major complications of transrectal prostate biopsy is 1%, especially when it is performed in patients who will not benefit from that biopsy.