Maternal Autoantibodies Research Articles

Abnormal mTOR Signaling Pathway Activity in Autism Spectrum Disorders: Prospects of Mechanism-Based Therapy

Autism spectrum disorder (ASD) is a developmental disorder characterized by the early onset of problems with communication, learning, and behavior. The syndromic form of ASD is caused by monogenic mutations. When it is not possible to find genetic or other known mechanisms, the term "idiopathic autism" is used. A significant part of both syndromic and idiopathic autism is associated with translational deregulation dependent on the mechanistic target of rapamycin (mTOR). In this review, we present both bioinformatic and experimental data that link the mTOR signaling pathway to maternal autoantibody related autism and childhood autoimmune neuropsychiatric disorders such as Sydenham's chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). The need for ASD subtyping and the prospects of mechanism-based therapy with inhibitors of the mTOR signaling pathway are also discussed.

Maternal synapsin autoantibodies are associated with neurodevelopmental delay.

Maternal autoantibodies can be transmitted diaplacentally, with potentially deleterious effects on neurodevelopment. Synapsin 1 (SYN1) is a neuronal protein that is important for synaptic communication and neuronal plasticity. While monoallelic loss of function (LoF) variants in the SYN1 gene result in X-linked intellectual disability (ID), learning disabilities, epilepsy, behavioral problems, and macrocephaly, the effect of SYN1 autoantibodies on neurodevelopment remains unclear. We recruited a clinical cohort of 208 mothers and their children with neurologic abnormalities and analyzed the role of maternal SYN1 autoantibodies. We identified seropositivity in 9.6% of mothers, and seropositivity was associated with an increased risk for ID and behavioral problems. Furthermore, children more frequently had epilepsy, macrocephaly, and developmental delay, in line with the SYN1 LoF phenotype. Whether SYN1 autoantibodies have a direct pathogenic effect on neurodevelopment or serve as biomarkers requires functional experiments.

Clinical Characteristics and Mid-term Follow-up in Children with Isolated Complete Atrioventricular Block.

Isolated complete atrioventricular block is a rare disease often associated with maternal autoantibodies. This study aimed to present the midterm data of patients at our clinic diagnosed with isolated complete atrioventricular block. We evaluated 108 patients diagnosed with isolated complete atrioventricular block. Demographic data of the patients, electrocardiography, echocardiography, 24-hour Holter monitoring data, and follow-up and complications of the patients who underwent pacemaker implantation were evaluated retrospectively. The mean age of the patients at diagnosis was 5.51 ± 5.05 years. At the time of diagnosis, 74.8% of the patients had no symptoms associated with complete atrioventricular block. The most common symptom was fatigue. Pacemaker implantation was needed in 88 (81.4%) patients during follow-up. Significant bradycardia was the most common pacemaker implantation indication. The mean battery life was 5.41 ± 2.65 years. The battery replacement-free period of 68 patients who underwent pacemaker implantation and continued their follow-up was 4.18 ± 2.89 (0.1-10) years. Pacemaker-related complications developed in 8 patients during follow-up. Left ventricular dysfunction developed (dyssynchrony induced) in 3 patients at follow-up, and all were paced from the right ventricular anterior wall. Those patients underwent cardiac resynchronization therapy and their left ventricular dysfunction improved. Isolated complete atrioventricular block is a rare disease requiring careful clinical follow-up. Patients are often asymptomatic and significant bradycardia is the most common indication for pacemaker implantation. Left ventricular dysfunction is an important cause of morbidity, especially in patients with right ventricular anterior wall pacing. Physicians should be aware of left ventricular dysfunction during follow-up. Cardiac resynchronization therapy should be considered as a treatment option for left ventricular dysfunction.

Plasmapheresis in Neonatal Lupus

About 2% of mothers with Sjögren’s syndrome and about 1% of mothers with systemic lupus erythematosus deliver a baby with a congenital heart block (CHB). This is thought to be as a result of the maternal autoantibodies that cross the placenta and cause congenital lupus in the fetus/neonate. Among patients with a 2nd or 3rd degree atrioventricular block, the mortality rate in the neonatal period is about 10%, and most neonates who survive require a pacemaker into adulthood. Despite the compelling mortality and morbidity, the data on the optimal preventive treatments are meager and not well-established. In addition to pharmaceutical therapy, one potentially effective therapy is plasmapheresis. Plasmapheresis is safe in pregnancy, well tolerated, and is effective in removing the offending substances in the serum which may cause disease. We review this literature, in order to educate the reader and to motivate interest in studying this condition in the future.

Altered cytokine levels in the cerebrospinal fluid of adult patients with autism spectrum disorder

BackgroundDespite intensive research, the etiological causes of autism spectrum disorder (ASD) remain elusive. Immunological mechanisms have recently been studied more frequently in the context of maternal autoantibodies and infections, as well as altered cytokine profiles. For the detection of immunological processes in the central nervous system, analyses of cerebrospinal fluid (CSF) are advantageous due to its proximity to the brain. However, cytokine studies in the CSF of ASD patients are sparse. MethodsCSF was collected from a patient sample of 24 adults (m = 16, f = 8, age: 30.3 ± 11.6 years) with ASD and compared to a previously published mentally healthy control sample of 39 neurological patients with idiopathic intracranial hypertension. A magnetic bead multiplexing immunoassay was used to measure multiple cytokines in CSF. ResultsSignificantly decreased interferon-γ-induced protein-10 (p = 0.001) and monocyte chemoattractant protein-1 (p = 0.041) levels as well as significantly higher interleukin-8 levels (p = 0.041) were detected in patients with ASD compared with the control group. ConclusionThe main finding of this study is an altered cytokine profile in adult patients with ASD compared to the control group. This may indicate immune dysregulation in a subgroup of adult ASD patients. Further studies in larger cohorts that examine a broader spectrum of chemokines and cytokines in general are needed to detect possible specific immune signatures in ASD.

Management of fetal hyperthyroidism caused by persistent autoimmune antibodies in a case of previously treated maternal Graves' disease.

Maternal Graves' autoantibodies are well known to cause fetal and neonatal thyroid disturbances. Despite radioiodine therapy, Graves' autoantibodies are known to persist, which can cross the placenta and cause hyperthyroidism in the fetus. We present the case of a 26-year-old woman in her first pregnancy, clinically and biochemically euthyroid with history of treated Graves' disease, where the fetus showed signs of hyperthyroidism on antenatal scans. This was confirmed by amniotic fluid testing as fetal blood sampling was not feasible and successfully treated with maternal carbimazole whilst continuing thyroxine for the mother (block-replacement). We discuss the challenges in the diagnosis of fetal hyperthyroidism and treatment whilst maternal thyroid status is maintained on thyroxine.

A Case of Neonatal Lupus Presenting with Myocardial Dysfunction in the Absence of Congenital Heart Block (CHB): Clinical Management and Brief Literature Review of Neonatal Cardiac Lupus

Neonatal lupus (NLE) is a rare acquired autoimmune disorder caused by transplacental passage of maternal autoantibodies to Sjogren’s Syndrome A or B (SSA-SSB) autoantigens (Vanoni et al. in Clin Rev Allerg Immunol 53:469–476, 2017) which target fetal and neonatal tissues for immune destruction. The cardiac trademark of NLE is autoimmune heart block, which accounts for more than 80% of cases of complete atrioventricular heart block (AVB) in newborns with a structurally normal heart (Martin in Cardiol Young 24: 41–46, 2014). NLE presenting with cardiac alterations not involving rhythm disturbances are described in the literature, but they are rare. Here, we report a case of a neonate with high anti-SSA antibodies who developed severe ventricular dysfunction in the absence of rhythm abnormalities, endocardial fibroelastosis, and dilated cardiomyopathy (Trucco et al. in J Am Coll Cardiol 57:715–723, https://doi.org/10.1016/j.jacc.2010.09.044, 2011), the most common cardiac presentations of NLE. The patient developed severe multiorgan dysfunction syndrome that required prolonged critical care support but fully recovered and was discharged home. We highlight the unusual clinical features of this NLE case and the importance of timely treatment of NLE allowing complete recovery of a critically ill neonate.

Neonatal Lupus presenting with neonatal hemochromatosis-like liver disease that responded to steroids: a case report

BackgroundNeonatal lupus erythematosus is a rare multisystem autoimmune disorder that predominantly involves the heart with congenital heart block but can involve other organs including the liver. The disease results from passage of maternal autoantibodies to the fetus and manifests in various forms depending on the organ involved. Neonatal lupus liver disease manifestations range from benign elevation in aminotransferases to fatal hepatic insufficiency with iron deposition that does not respond to therapy. Only a handful of cases have been reported to date. The antibodies implicated are Sjogren Syndrome types A and B antibodies. Other non-specific autoantibodies can be positive as well such as antinuclear antibodies. Smooth muscle antibodies are classically considered specific to autoimmune hepatitis, and while they have been described in other chronic liver diseases, they have not been described in neonatal lupus liver disease. Herein we report a rare case of neonatal cholestasis due to neonatal lupus liver disease that presented with a positive smooth muscle antibodies in addition to a biochemical picture of neonatal hemochromatosis, with a remarkably elevated ferritin, that responded well to steroid therapy. Case presentationAn 8-day old full-term baby girl was referred to our center for evaluation of neonatal bradycardia and generalized jaundice that started in the first day of life. Prenatal history was significant for fetal bradycardia. Examination was unremarkable except for bradycardia and generalized jaundice. Laboratory findings included elevated alanine aminotransferase, aspartate aminotransferase, Alkaline Phosphatase, and total and direct bilirubin. Her ferritin was markedly elevated along with triglycerides. Sjogren syndrome antibodies were positive in addition to antinuclear and anti-smooth muscle antibodies. The diagnosis of cardiac neonatal lupus was given, and her liver disease was attributed to lupus despite the biochemical picture of neonatal hemochromatosis. She was started on oral prednisolone for which her liver function parameters showed a dramatic response and continued to be within the normal limits several weeks after discontinuation of steroids.ConclusionNeonatal lupus liver disease is a rare cause of neonatal cholestasis that can rarely present with neonatal hemochromatosis picture which unlike other causes of neonatal hemochromatosis can be reversed with steroid therapy.

PSAT271 The Impact of Maternal Autoimmune thyroid disease on neonatal thyroid conditions in Urban City Population

Abstract Background There is a wide spectrum of maternal autoimmune thyroid disorders (AITD) in pregnancy ranging from Graves’ hyperthyroidism (GD) to Hashimoto thyroiditis (HT), both of which share similar immunological properties. A variety of maternal thyroid autoantibodies can cross transplacentally which may potentially cause varying degrees of neonatal thyroid dysfunction. Objective To study the neonatal outcomes of thyroid function in mothers with AITD in urban setting. Methods Mothers with AITD and newborns were included for retrospective analysis over 12 months. AITD encompassed all mothers diagnosed prior/during pregnancy with either HT or GD. Results Maternal Data: A total of 147 mothers were included (HT 87%, GD 13.6%). Among mothers with HT, thyroid auto-Abs were tested in 51/127 (40%) mothers, of which 32/47(68%) were positive for TPO, 11/21(2%) positive for ATA, 2/6(33%) positive for TSI, 1/2 (50%) positive for TRAb. L-Thyroxine was administered to 90% HT mothers. Among mothers with GD, thyroid auto-Abs were tested in 17/20 (85%) mothers, of which 7/17(41%) were positive for TSI, 6/10(60%) positive for TRAb, 7/14(50%) were positive for TPO, 3/5 positive for ATA. Methimazole (MMI) was administered to 25% GD mothers. Neonatal outcome: A total of 150 neonates (115 FT, 35 PT) were born to AITD mothers. Newborn screen was abnormal in 2 infants. 7 neonates (4.6%) were tested for thyroid auto-Abs, of which 1/2 was positive for TPO, 1/2 positive for ATA, 3/3 negative for TSI, 5/5 negative for TRAb. Serum TFTs were performed in 62/150 neonates; majority 57/62(92%) were normal, 3 had mild compensated hyperthyrotropinemia (mean TSH 17.1 mIU/L, FT4 1.93 ng/dl) and were followed elsewhere. 2 neonates developed congenital hypothyroidism requiring L-Thyroxine. Infant 1: TSH 4.56mIU/L, FT4 1.1 ng/dl, TPO and ATA positive on DOL7 and had ectopic thyroid, infant born to TPO positive HT mother on Synthroid. Infant 2: TSH 149.5mIU/L, FT4 0.8 ng/dl, TSI negative on DOL7 and had hyperemic thyroid, born to TSI, TPO and TRAb positive GD mother on MMI. Overall, only 3.3% of neonates had evidence of thyroid function abnormality which may have either been transient or permanent. Conclusion Although rare, mothers with AITD might potentially impair neonatal thyroid function. This may be due to various thyroid auto-Abs or anti- thyroid medication that cross transplacentally. Maternal history of AITD should therefore raise suspicion to screen neonates and thus warrants continued vigilance. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Neonatal alloimmune neutropenia: diagnosis and management of 31 Italian patients.

In neonates, antibody-mediated destruction of neutrophils may occur as a consequence of auto- or isoimmune disorders. There are few studies on this topic, and particularly on neonatal alloimmune neutropenia (NAN). We retrospectively evaluated the clinical and molecular/serological findings of 83 neutropenic infants referred to our Reference Laboratory for diagnostic evaluation of NAN, from 2008 to 2021. We also genotyped 260 Italian healthy subjects for the four principal human neutrophil antigens (HNA). The diagnosis of NAN was confirmed in 31 cases. The other 52 cases were autoimmune neutropenia (n=21), neutropenia caused by maternal neutrophil autoantibodies (n=8), neutropenia of non-immune origin (n=17), and cases in which a diagnosis could not be reached (n=6). The median age at neutropenia onset and absolute neutrophil count (ANC) were significantly lower in NAN than in non-NAN cases (1 vs 30 days, p<0.005; 330 vs 580/μL, p=0.003, respectively). About 74% of NAN cases developed neutropenia within the first week of life and laboratory investigations were required within 2 weeks. In five patients the neutropenia was discovered at the end of the first month of life and they were referred to our laboratory 1-2 months later when neutropenia had already resolved. Infections were seen in 19% of NAN cases. The median time to resolution of NAN was 31 days. About 50% of NAN cases were due to alloantibodies against HNA-1b, the most frequent allele of HNA-1 in the Italian population (allele frequency 0.63). In five cases of NAN the mothers had an HNA-1 null phenotype, a frequency higher than that observed in our Italian cohort. NAN should be considered by clinicians in infants with neutropenia onset within 5-7 days of life, even though there can be other reasons for a low ANC. If neutropenia is detected later, benign neutropenia seems more likely, although persistence of maternal alloantibodies cannot be ruled out.

Transient pseudothrombocytopenia (PTCP) in the neonate due to the mother.

Thrombocytopenia with platelet count <50×109/L is common laboratory finding in a severely ill newborn in neonatal intensive care units (ICU). Neonates with severe thrombocytopenia are at risk of bleeding. Most dangerous is intracerebral hemorrhage (ICH) frequently leading to death or lifelong neurological sequels. Pseudothrombocytopenia (PTCP) is a rare in vitro phenomenon of falsely low platelet count determined on hematology analyzers due to platelet clumping in ethylenediaminetetraacetic acid (EDTA) anticoagulated blood. PTCP was also reported in pregnant women with isolated thrombocytopenia. EDTA-PTCP in the neonate due to the transplacental transmission of maternal antibodies has been reported only in a few cases. Although PTCP is rare phenomenon, it should always be excluded in newborns with isolated thrombocytopenia to avoid erroneous interpretation of platelet and leukocyte count, unnecessary laboratory investigation of false positive antiplatelet antibodies and needless platelet transfusions. We report on two cases of transient PTCP in a neonate due to transplacental transfer of maternal EDTA-dependent autoantibodies of IgG class from the same mother.

P1525: MANAGEMENT OF AUTOIMMUNE HAEMOLYTIC ANAEMIA DURING PREGNANCY OR POST-PARTUM: AN INTERNATIONAL MULTI-CENTRE EXPERIENCE.

Background: Autoimmune haemolytic anaemia (AIHA) during pregnancy is a rare finding, and few is known about maternal and foetal outcomes. AIHA may either develop or relapse during gestation and postpartum or be an issue in a patient on active therapy who becomes pregnant. AIHA management during pregnancy and lactation is not standardized and drug use is often limited by safety concerns. Aims: We studied AIHA impact on pregnancy focusing on disease severity, treatment need and maternal/foetal outcome. Methods: Through a multicentric retrospective cohort study, we identified 38 pregnancies occurred in 28 women from 1997 to 2021 in 10 European centres in Italy, Denmark, France, the Netherlands, USA, and Spain. All included patients had a previous AIHA history or developed/exacerbated AIHA during gestation or postpartum. AIHA was classified according to the direct antiglobulin test. Results: We registered 18 warm AIHA (10 IgG; 8 IgG+C3d), 2 cold agglutinin disease, 3 mixed and 5 atypical forms (Table 1). Evans syndrome (i.e., association of AIHA and immune thrombocytopenia or neutropenia) was present in 4. Mean age at AIHA diagnosis was 27 (3-39) and at pregnancy 32 (21-41) years. AIHA diagnosis predated pregnancy in 15 women and had required at least 1 therapy line in all of them, and ≥2 lines in 12 (rituximab, N=7; cytotoxic immunosuppressants, N=6; splenectomy, N=5). Among these 15 patients, 6 had a relapse during pregnancy, 3 during postpartum and 9 were on active treatment at the time of pregnancy (steroids, N=8; cyclosporine, N=1; azathioprine, N=1; the latter stopped after positive pregnancy test). A patient with a previous AIHA, relapsed as immune thrombocytopenic purpura during pregnancy. Further 8 patients had an AIHA onset during gestation and 2 postpartum. A patient had AIHA onset during the postpartum of the 1st pregnancy and relapsed during the 2nd one. In the 20 women experiencing AIHA during pregnancy/postpartum, median Hb and LDH levels were 6,4 g/dL (3,1 – 8,7) and 588 UI/L (269-1631), respectively. Management consisted in blood transfusions (N=10) and prompt establishment of steroid therapy+/-IVIG (N=20), all with response (complete N=13, partial N=7). After delivery, rituximab was necessary in 4 patients and cyclosporine was added in one. Anti-thrombotic prophylaxis was given in 7 patients. Overall, we registered 10 obstetric complications (10/38, 26%), including 4 early miscarriages, a premature rupture of membranes, a placental detachment, 2 preeclampsia, a postpartum infection and a biliary colic. Apart from the case of biliary colic and one of the two cases of preeclampsia, 8/10 complications occurred during active haemolysis and treatment for AIHA. Nine foetal adverse events (9/38, 24%) were reported: a transitory respiratory distress of the new-born in a mother with active AIHA, 3 cases of foetal growth restriction, a preterm birth, an infant reporting neurologic sequelae, a case of AIHA of the new-born requiring intravenous immunoglobulins, blood transfusions and plasma exchange, and 2 perinatal deaths. The latter both occurred in women on active AIHA therapy and were secondary to a massive placental detachment and a symptomatic SARS-CoV-2 infection. Image:Summary/Conclusion: AIHA developing/reactivating during pregnancy or postpartum is rare (about 5%) but mainly severe requiring steroid therapy and transfusions. Importantly, severe maternal and foetal complications may occur in up to 26% of cases mostly associated with active disease, pinpointing the importance of maintaining a high level of awareness. Passive maternal autoantibodies transfer to the foetus seems a rare event.

Association of thyroid dysfunction and autoantibody positivity with the risk of preterm birth: a hospital-based cohort study.

BackgroundEvidence for the association of thyroid dysfunction and autoantibody positivity with preterm birth remains controversial. We aimed to study the association of maternal thyroid dysfunction and autoantibody positivity with the risk of preterm birth.MethodA hospital-based cohort study of 40,214 women was conducted. Gestational age-specific percentiles of the FT4 and TSH concentrations were used for the definition of thyroid dysfunction. Autoantibody positivity was identified when the concentration > the threshold. The association of thyroid dysfunction and autoantibody positivity with the risk of preterm birth was estimated.ResultsNo significant higher risk of preterm birth was found for women with variants of thyroid dysfunction or autoantibody positive than euthyroid women. Sensitivity and stratification analyses indicated that thyroperoxidase antibody (TPOAb) positivity in the first trimester (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17–1.90) and overt hypothyroidism restricted to women negative for TPOAb (OR, 4.94; 95%CI: 1.64–14.84) was associated with an increased risk of preterm birth. Modification effects of gestational age were found for women who had the test ≤18 and > 18 weeks. Continuous FT4 measurements tested ≤18 weeks of gestation were associated with a higher risk of preterm birth (OR, 1.13, 95% CI: 1.00–1.28), while a negative relationship for FT4 concentrations tested > 18 weeks of gestation (OR = 0.68, 95% CI: 0.48–0.97).ConclusionsSome specific thyroid function abnormalities were associated with an increased risk of preterm birth. Interaction between gestational age and FT4 concentration on the risk of preterm birth was identified, with a critical node of 18 weeks of gestation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-022-04806-9.

Maternal autoantibody profiles as biomarkers for ASD and ASD with co-occurring intellectual disability

Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) cross the placenta, access the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in the exposed offspring. We previously reported maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1, and YBOX) and that reactivity to nine specific combinations of these proteins (MAR ASD patterns) was predictive of ASD risk. The aim of the current study was to validate the previously identified MAR ASD patterns (CRMP1 + GDA, CRMP1 + CRMP2, NSE + STIP1, CRMP2 + STIP1, LDHA + YBOX, LDHB + YBOX, GDA + YBOX, STIP1 + YBOX, and CRMP1 + STIP1) and their accuracy in predicting ASD risk in a prospective cohort employing maternal samples collected prior to parturition. We used prenatal plasma from mothers of autistic children with or without co-occurring intellectual disability (ASD = 540), intellectual disability without autism (ID = 184) and general population controls (GP = 420) collected by the Early Markers for Autism (EMA) study. We found reactivity to one or more of the nine previously identified MAR ASD patterns in 10% of the ASD group compared with 4% of the ID group and 1% of the GP controls (ASD vs GP: Odds Ratio (OR) = 7.81, 95% Confidence Interval (CI) 3.32 to 22.43; ASD vs ID: OR = 2.77, 95% CI (1.19–7.47)) demonstrating that the MAR ASD patterns are strongly associated with the ASD group and could be used to assess ASD risk prior to symptom onset. The pattern most strongly associated with ASD was CRMP1 + CRMP2 and increased the odds for an ASD diagnosis 16-fold (3.32 to >999.99). In addition, we found that several of these specific MAR ASD patterns were strongly associated with ASD with intellectual disability (ASD + ID) and others associated with ASD without ID (ASD-no ID). Prenatal screening for these MAR patterns may lead to earlier identification of ASD and facilitate access to the appropriate early intervention services based on each child’s needs.

MATERNAL AUTOANTIBODIES AS A POSSIBLE ASD-RISK BIOMARKER

Abstract Maternal autoantibody-related ASD (MAR ASD) is a subtype of autism in which pathogenic maternal autoantibodies (IgG) can cross the placenta, access the developing brain, and cause neurodevelopmental alterations and behaviors associated with autism in the exposed offspring. We previously reported maternal IgG response to eight proteins (CRMP1, CRMP2, GDA LDHA, LDHB, NSE, STIP1, and YBOX) and that reactivity two or more specific proteins (MAR ASD patterns) can be used to predict ASD risk in a discovery study. Objective In the current study, we aimed to validate the previously described MAR ASD patterns (CRMP1+GDA, CRMP1+CRMP2, NSE+STIP1, CRMP2+STIP1, LDHA+YBOX, LDHB+YBOX, GDA+YBOX, STIP1+YBOX, and CRMP1+STIP1) and their accuracy to predict ASD risk in a prospective cohort. Methods We used plasma from mothers of autistic children (ASD= 540) and general population controls (not verified as typically developing) (GP=420) collected by the Early Markers of Autism (EMA) study. We evaluated maternal IgG reactivity against each of the eight fetal brain proteins by ELISA and used Fisher Exact Test (p &amp;lt; 0.05) to compare the association for each pattern with child outcome (ASD vs GP). Results We found reactivity to at least one protein in more than 50% of the samples in the case and control groups, suggesting that reactivity to a single antigen is not diagnosis-specific. However, when we tested the nine previously identified MAR ASD patterns, we found highly-specific reactivity in 10% ASD group vs 1% of the GP controls and increased the odds for an ASD outcome nearly 8-fold (p&amp;lt; 0.001, OR 7.81, 95% CI from 3.32 to 22.43) demonstrating that the MAR ASD patterns are highly specific for the case group and could be used to assess ASD risk prior to symptoms. Supported by EPA2P01ES011269-11, 83543201, R01ES015359, NICHD funded IDDRC P50 (P50HD103526), CONACYT-UC MEXUS Doctoral Fellowships 2015.

Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function

ObjectiveNeonatal lupus erythematosus (NLE) may develop after transplacental transfer of maternal autoantibodies with cardiac manifestations (congenital heart block, CHB) including atrioventricular block, atrial and ventricular arrhythmias, and cardiomyopathies. The association...

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

A Male Infant with Cholestatic Jaundice, Hemolytic Anemia, and Thrombocytopenia.

Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication and behavioral problems. ASD is highly heritable; however, environmental factors also play a considerable role in this disorder. A significant part of both syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.

Osteomyelitis and septic arthritis in neonatal lupus erythematosus patients

Osteomyelitis in neonates is quite uncommon and often appears without a typical sign. Clinicians' late diagnosis and inappropriate treatment may result in severe sequelae. We report a rare case of osteomyelitis and septic arthritis infant with a mother's previous medical history of systemic lupus erythematosus at nine years old. Anti Lupus Anticoagulant (LA) result shows the infant also suffers from neonatal lupus erythematosus (NLE). Early diagnosis and proper management of the patient may produce better outcomes. • The association of osteomyelitis with Neonatal Lupus Erythematosus (NLE) is infrequent. It is suspected that the infection triggered by transplacental transmission of maternal autoantibody that cause immune suppression of the bone marrow. • Klebsiella pneumoniae is the most common cause of nosocomial infection and potentially cause septic arthritis. Antibiotic treatement should be initiated early. • Early diagnosis and treatment are critical since osteomyelitis and NLE may directly affect the patient's growth, development, and quality of life in the future.

253 Imaging of congenital AV block caused by maternal autoantibodies: a single-centre experience

Abstract Aims Autoimmune congenital heart block (CHB) is a severe manifestation of neonatal lupus syndrome. There is lack of consensus regarding treatment of pregnant women with anti-SSA/SSB autoantibodies. To evaluate the effectiveness of the combined protocol therapy (oral steroid, plasmapheresis, and IVIG) for the CHB treatment. Methods and results All cases of CHB from 2000 to 2020 were retrospectively enrolled. All the patients underwent foetal echocardiography for the evaluation of CHB, ventricular rate and main related foetal complications: cardiomegaly, pericardial and pleural effusion, foetal hydrops, dilated cardiomyopathy, and heart failure. Moreover, postnatal major adverse cardiovascular, such as death and pacemaker implantation, were recorded. For statistical analysis, the population was divided into two cohorts: a protocol group receiving in utero combined therapy and a control group receiving other therapies or not treated. Among 252 pregnancies with anti-SSA/SSB antibodies, 36 developed CHB. At birth, complete CHB treated with protocol therapies showed a significantly higher ventricular rate (P = 0.042), a significant reduction in intrauterine or postnatal mortality (P = 0.018), and a lower rate of pacemaker implantation (P = 0.049). Conclusions The combined treatment protocol has proven effective in improving foetal and neonatal short- and long-term survival.