Activación inmune durante el embarazo y riesgo de Trastorno del Espectro Autista / Maternal immune activation and risk of Autism Spectrum Disorder

Resumen: En los últimos años se ha intentado comprender la etiología del Trastorno del Espectro Autista (TEA), evidenciandose que existe una compleja interacción entre factores genéticos y ambientales. Estudios epidemiológicos y en modelos animales sugieren que la activación inmune de la madre durante el embarazo puede asociarse un mayor riesgo de desarrollar TEA en los hijos, destacando el rol de las citoquinas proinflamatorias, los auto-anticuerpos y el rol de la microglia activada en la poda sináptica durante el desarrollo embrionario. Comprender mejor los factores asociados con los Trastornos del Neurodesarrollo permitirá en el futuro desarrollar estrategias de manejo y detección precoz en población de riesgo.

Abstract: Autism Spectrum Disorder (ASD) etiology has been related whit complex interaction between ge netic and environmental factors. In the last years, numerous studies have suggested that maternal immune activation during pregnancy could be related to ASD in the offspring. This relation could be explained by the effects of pro-inflammatory cytokines, autoantibodies and microglial synap tic pruning during early embryonic development. Better understanding of Neurodevelopmental Disorders risk factors will support appropriate strategies of screening and management of risk population.

Altered Tregs and oxidative stress in pregnancy associated lupus

Abstract Aim SLE is a systemic autoimmune disease generally affecting woman in the reproductive age. It is associated with an altered level of Tregs and oxidative stress while an increase in Tregs, and different antioxidant mechanisms to combat oxidative stress are essential for successful pregnancy. Hence, this study aims to determine the level of CD4+ and CD8+ Tregs and oxidative stress in pregnant lupus patients. Methods Ten healthy and 10 pregnant lupus volunteers from the North Indian population, within the age group of 20-30 years were enrolled in the study. All the patients were non-smokers, non-alcoholics and were not associated or undergoing therapy for any other disease. They had a SLEDAI of 37.4 ± 7.32 with 5.2 ± 1.93 years of disease duration. Oxidative stress was determined by measuring the enzyme activity of anti-oxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and the level of reduced glutathione and lipids peroxidised, spectrophotometrically. Flowcytometry was performed for immunophenotyping to determine CD8+ and CD4+ Tregs. Results Elevated CD8+ Tregs and diminished CD4+ Tregs were observed in pregnant lupus patients. Oxidative stress was significantly increased as the activities of anti-oxidant enzymes and level of reduced glutathione was considerably diminished. There was a substantial increase in the amount of lipids peroxidised. Conclusion Pregnant lupus patients undergo considerable level of oxidative stress in comparison to healthy pregnant woman. The decreased level of CD4+ Tregs and an increase in CD8+ Tregs might be another important factor responsible for pregnancy associated complications. Hence, lupus leads to alterations in the necessary conditions for a successful pregnancy, which might eventually cause higher mortality, morbidity and associated complications.

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage

Antinuclear antibodies [ANAs] in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. ANAs were detected in 74 of 560 [13.21%] patient with recurrent miscarriage, and in only 5 of 560 [0.9%] controls [p<0.001]. ANA positivity was generally found with low-positive results [1.40-1.80] in about 38% of positive cases, whereas moderate titres [1.160-1.320] and high titres [>1.640] were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients

Búsqueda prenatal de bloqueo aurículo ventricular congénito en población de riesgo: experiencia Universidad Católica de Chile / Congenital heart block in risk population: Universidad Catolica de Chile experience

Congenital heart block is a fetal arrhythmia detected by routine prenatal ultrasound. Natural history and risk factors for this condition are known. Patients having Ro/La antibodies have 2 to 4 percent risk of affected child and recurrence of up to 25 percent. There are standarized protocols for measuring the PR interval by ultrasound, as well as reference curves for different gestational ages. The experience at Hospital Clínico de la Universidad Católica de Chile is reported, describing follow up of 37 patients over a period of more than 4 years. A protocol based on monthly monitoring of risk group was adopted.

El bloqueo aurículo ventricular congénito constituye una de las arritmias fetales detectables mediante ultrasonido prenatal de rutina. Se conoce su evolución natural y la población de riesgo de sufrir esta afección. En portadoras de anticuerpos Ro/La el riesgo de un hijo afectado es entre 2 y 4 por ciento, y la recurrencia de hasta un 25 por ciento. Existen protocolos estandarizados para medir el intervalo PR mediante ultrasonido, como también curvas de referencia para las distintas edades gestacionales. Reportamos la experiencia en el Hospital Clínico de la Universidad Católica de Chile, con un seguimiento de 37 pacientes en un periodo de más de 4 años. Se adoptó un protocolo de seguimiento mensual del grupo de riesgo.

Pemphigus vulgaris during pregnancy - a case report

Pemphigus vulgaris [PV] is an uncommon immune-mediated bullous dermatosis which is very rare during pregnancy. Its management during pregnancy is a challenge and sometimes very difficult. Only few cases have been reported in literature so far. The disease may be associated with adverse fetal outcomes such as prematurity and fetal death. The neonate can develop transient skin lesions. We present a case of a patient who conceived during the active phase of PV required high doses of corticosteroids and delivered a preterm appropriate for gestation age newborn

Gestante con pénfigo foliáceo endémico y producto libre de enfermedad: Caso clínico / Endemic pemphigus foliaceus in a pregnant woman: Report of one case

Endemic pemphigus foliaceus (EPF) in an autoinmune skin disease present in areas of the Amazonia. We report a 36 year-old woman who presented EPF at 17 weeks of pregnancy. At 29 weeks, she started antimicrobial treatment and steroids. At the moment of delivery, the disease was in remission and cutaneous lesions were not seen in the neonate. Indirect immunofluorescence titers of total IgG in the mother and in the neonate were negative. Sixteen months later, IgG titers in the offspring were 1/20 and remained negative in the mother, who was on low doses of oral corticosteroids (Rev Méd Chile 2009; 137: 1205-8).

Manipulation of cytokine production profiles as a therapeutic approach for immunologic pregnancy loss.

Pregnancy is not as successful as one might think; it can be compromised by several complications such as recurrent spontaneous miscarriage, pre-term delivery, pre-eclampsia etc. Much attention has been paid to the possibility of the maternal immune system mediating deleterious effects on pregnancy. Research conducted during the last two decades has shed much light on cell-mediated immunologic effectors that might underlie these pregnancy complications. Of particular interest are the effects that pro-inflammatory and anti-inflammatory cytokines have on the foetus and placenta, and thus on the success and failure of pregnancy. This review presents evidences that certain cytokine profiles are associated with recurrent miscarriage and pre-term delivery and discusses possible pathways of effector function of cytokines in pregnancy loss and the redirection of cytokine profiles from one that is antagonistic to pregnancy towards one that is conducive to the success of pregnancy. Among the promising agents for the modulation of the Th1/Th2 balance are progestogens like progesterone and dydrogesterone; this review also discusses recent evidence that progestogens are capable of modulating cytokine production patterns in pregnancy loss.

Placental transfer of Haemophilus influenzae type b antibodies in malnourished pregnant women

This study evaluated the vaccination response to Haemophilus influenzae type b (Hib) in malnourished pregnant women (MN), cord blood (CB) and in infants at two and six months of age for comparison with a control group (C). Twenty-eight malnourished pregnant women and 29 pregnant controls were immunized with conjugated Act-HIB® in the third trimester of pregnancy. Blood samples were collected from all before the immunization, during labor (post immunization), and from CB. All infants were immunized with Hib vaccine according to normal vaccine schedule and sera were collected at two and six months of age. Antibody levels to polyribosylribitol phosphate (PRP) were similar for both groups. Preimmunization: MN 1.94 µg/mL, C 1.68 µg/mL; post-vaccination: MN 18.53 µg/mL and C 17.55 µg/mL; in CB from MN 14.46 µg/mL and from C 17.04 µg/mL. Infants from MN and C mothers presented respectively at two months: 5.18 µg/mL and 8.60 µg/mL and at six months: MN 3.42 µg/mL and C 2.18 µg/mL. Antibody levels were similar in both groups studied (p = 0.485), however the vertical transmission rate was 14 percent lower in the MN pregnant group. Levels of antibodies > 0.15 µg/mL were found in all newborns from the MN pregnant group. Pregnant MN presented an immunological response to Hib vaccine similar to group C, however, vertical transmission rate of antibodies to PRP in the MN pregnant group was 14 percent lower than that in C, suggesting a less efficient passage of antibodies within this group.

Avances sobre síndrome antifosfolípido / Advances in antiphospholipid syndrome

El Síndrome antifosfolípido (SAF) es una trombofilia adquirida, que se caracteriza por presentar eventos trombóticos recurrentes y complicaciones obstétricas en presencia de anticuerpos antifosfolípidos (aFL), los cuales son pesquisados por pruebas de laboratorio como anticoagulante lúpico y anticuerpos anticardiolipina. En esta revisión se muestran los aspectos más relevantes del SAF, destacando los avances en fisiopatología y criterios diagnósticos.

Lupus y embarazo: consideraciones en relación a situaciones críticas / Lupus and pregnancy: critical situations considerations

There is a reciprocal relationship between lupus and pregnancy, which implies greater risk for both mother and fetus, and even though this was very important until the middle of the last century, it has currently decreased significantly due to increased awareness of the disease, its treatment, and when certain basic conditions are considered prior to conception. It is also important to unserstand situations that increase risk, as well as others that are completely contrary to pregnancy. Nevertheless, a well-planned pregnancy is not always the case and different courses of action must be adequately implemented if needed. We review options when faced with pregnancy with lupus, in presence of antiphospholipids, when the mother is a carrier of anti-Ro and anti-La antibodies; and finally the problems of pregnancy with arterial hypertension and proteinuria. We emphasis the importance of a close relation between rheumatologists and gynecologist/obstetricians, and conclude that the more informed we are, both in terms of the disease itself and the risks implied for a pregnant women with lupus, the better we can treat and face this situation with tranquility and optimism.

Seronegative neonatal myasthenia gravis in one of the twins.

Neonatal myasthenia gravis has been described as a transient condition affecting only a small percent of neonates. We report a twin gestation in a seronegative mother with myasthenia gravis, in which only one twin was affected.

Pregnancy outcome in women with antiphospholipid syndrome and alloimmunity: a case report

CONTEXTO: Mulheres com síndrome do anticorpo antifosfolípide e aloimunidade têm um mau prognóstico de gravidez. Existem muitas opções para o diagnóstico e o tratamento destas doenças, embora o tratamento mais adequado não esteja estabelecido. RELATO DE CASO: Apresentamos a evolução clínica e o tratamento de uma mulher com antecedentes de dois abortos e que vem sendo acompanhada, há 10 anos, em nosso serviço. Após o diagnóstico da síndrome do anticorpo antifosfolípide e de aloimunidade, a paciente recebeu tratamento com heparina, aspirina e prednisona, além de imunizações com linfócitos. Nas duas gravidezes subseqüentes, teve dois bebês prematuros, que evoluíram com crescimento e desenvolvimento normais. A quinta gravidez não foi bem-sucedida, apesar de a paciente ter recebido um tratamento semelhante ao utilizado previamente embora após o início da gravidez, não planejada. Na discussão deste caso, enfatizamos os mecanismos patogênicos e o tratamento destas doenças.

Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population.

Placental malaria infection jeopardizes pregnancy outcome, and its influence may also impair the transplacental transfer of some antibodies. Two hundred and thirteen Gambian mother-baby pairs were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinaemia on transplacental transfer of measles and tetanus antibodies in Gambian population. Placental blood and tissue were collected for placental malaria diagnosis. Cord and maternal sera were tested for total IgG concentration by laser nephelometry and for IgG antibody to tetanus toxoid and measles by ELISA. The prevalence of placental malaria infection was 51.1%. Mothers whose placentae were parasitized had a significantly higher mean total serum IgG (22.0 g/L vs 11.3 g/L, p < 0.001) and measles antibody level (4.02 IU/mL vs 1.21 IU/mL, p < 0.01), but not tetanus antibody, than mothers with non-parasitized placentae. Results of multiple regression analysis showed that placental malaria infection and maternal hypergammaglobulinaemia were associated with the reduction of 72% (95% CI 67.84) and 86% (95% CI 76.91) in transplacental transfer of measles antibody respectively but did not influence the transfer of tetanus antibody. It is concluded that the combined influence of placental malaria infection and maternal hypergammaglobulinaemia is significantly associated with the transfer of impaired measles antibody in this population.

Toxoplasma andtibodies in normal and complicated pregnancy

A total of 70 women with complicated pregnancy and 20 ones with normal pregnancy [the control] was selected for this study. They were all RH positive and free from syphilis, brucellosis and malignancy. Both groups were subjected to a detection of antitoxoplasma antibodies levels by the indirect hemagglutination tests [IHAT-IgG] and by ELISA [IgG and IgM]. The results showed that all controls were IHA-IgG and ELISA-IgM negative, however two of them were ELISA IgG positive. Out of the women with complicated pregnancy, 97.1% were IHAT positive. Using ELISA, 81.4% were IHAT positive and 60% were IgM positive. The results revealed a significant difference between the complicated cases and controls

Anti Ro/SSA positive undifferentiated connective tissue disease in a mother with a newborn with complete congenital heart block: a case report.

An association between complete congenital heart block (CCHB) and anti-Ro/SSA antibody is well recognized but has never been reported in Thailand. We report here a 37-year-old female who was admitted because of massive epistaxis secondary to immune thrombocytopenia. She had given birth to a child with CCHB 2 years previously, when she was healthy. Antinuclear antibody and anti-Ro/SSA were positive in her sera, but were negative in her son. The relationship between anti-Ro/SSA antibody and outcome of mothers with infants with CCHB is reviewed.

Anticuerpos anticardiolipina en la preeclampsia/eclampsia / Anticardiolipine antibodies in preeclampsia/eclampsia

Introducción. Los anticuerpos antifosfolípidos se han encontrado elevados en pacientes con preeclampsia/eclamplsia. Objetivo. Determinar la presencia de anticuerpos anticardiolipina en pacientes con preeclampsia/eclampsia. Pacientes y métodos. Estudiamos prospectivamente 65 pacientes, 35 con preeclampsia/eclampsia (grupo problema, A) y 30 con embarazo normal (grupo control, B) en una UCI. Se efectuó determinación en sangre de IgM e IgG utilizando el método modificado de Harris al segundo y tercer trimestre de embarazo en los dos grupos. Resultados. Encontramos al 2o. y 3er. trimestre de embarazo: en el grupo A, lgG 1.3 ñ 0.9 U y 1.52 ñ 1.1, respectivamante (cuatro pacientes) y la lgM fue de 2.2 ñ 0.9 U y 2.06 ñ 0.81 U (nueve pacientes). En el grupo B (30 pacientes) la lgG fue 1.2 ñ 0.7 U y 0.2 ñ 0.1 U, y la lgM 2.1 ñ U y 1.7 ñ 1 U en los mismos periodos. Conclusión. Los anticuerpos anticardiolipinas se elevan frecuentemente en pacientes con preeclampsia/eclampsia

Inmunopatología del aborto temprano: lo actual / Immunopathology of early abortion: What is current

Se revisó la bibliografía relacionada al papel que juegan los mecanismo inmunopatológicos en el aborto temprano, señalando las principales teorías en especial lo referente al Complejo Principal de Histocompatibilidad (CPH) y a los antígenos TLX (Antígenos reacción cruzada trofoblasto/linfocito) los cuales despiertan una reacción antiidiotipo la cual si no sucede se produce un aborto. También mencionamos que los anticuerpos bloqueadores, células supresoras e interucinas (IL) bloquean el mecanismo inmune citotóxico contra el producto de la gestación. La terapia actual se menciona