Molecular Mechanisms of Fetal and Neonatal Lupus: A Narrative Review of an Autoimmune Disease Transferal across the Placenta.

This study, conducted by searching keywords such as "maternal lupus", "neonatal lupus", and "congenital heart block" in databases including PubMed and Scopus, provides a detailed narrative review on fetal and neonatal lupus. Autoantibodies like anti-Ro/SSA and anti-La/SSB may cross the placenta and cause complications in neonates, such as congenital heart block (CHB). Management options involve hydroxychloroquine, which is able to counteract some of the adverse events, although the drug needs to be used carefully because of its impact on the QTc interval. Advanced pacing strategies for neonates with CHB, especially in severe forms like hydrops, are also assessed. This review emphasizes the need for interdisciplinary care by rheumatologists, obstetricians, and pediatricians in order to achieve the best maternal and neonatal health in lupus pregnancies. This multidisciplinary approach seeks to improve the outcomes and management of the disease, decreasing the burden on mothers and their infants.

A Case Report of Neonatal Lupus Erythematosus with Liver Function Damage and Cytomegalovirus Colonization.

BACKGROUND: Neonatal lupus erythematosus (NLE) is an acquired autoimmune disease. NLE with liver function damage and cytomegalovirus colonization is rarely reported. METHODS: This case describes a newborn male's laboratory testing found sustained liver function damage when he came to see the doctor due to oral candidiasis. The cause was identified through clinical symptoms, laboratory tests, auxiliary examinations, and family history of the patient. RESULTS: The final diagnosis of the child was NLE with liver function damage and cytomegalovirus colonization according to comprehensive analysis and follow-up observation. CONCLUSIONS: NLE and cytomegalovirus colonization can both lead to liver function damage. When the organ function of newborns is abnormal, it is necessary to promptly investigate the cause and determine whether it is NLE.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block.

BACKGROUND: Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. OBJECTIVE: To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. METHODS: From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. RESULTS: Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. CONCLUSIONS: CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

ANTECEDENTES: El lupus neonatal (LN) es extremadamente raro y es ocasionado por el paso transplacentario de auto-anticuerpos maternos IgG contra las proteínas Ro, La y/o RNP a la circulación fetal que puede ocasionar bloqueo aurículo-ventricular completo congénito (BAVCC) permanente, lesiones dérmicas y afectación hepática. OBJETIVO: Conocer la prevalencia de LN en paciente con BAVCC y la evolución clínica en un seguimiento a largo plazo. MÉTODOS: De enero de 1992 a diciembre 2017 se incluyeron paciente con BAVCC. La presencia de anticuerpos antinucleares anti-SSA/Ro y anti-SSB/La en suero materno confirmó LN. RESULTADOS: Ocho pacientes fueron incluidos con seguimiento de 10 ± 6 años, el 62.5 % con LN; dos fueron del sexo masculino. Uno diagnosticado in útero, dos al nacimiento, en ellos se implantó marcapaso; uno a los 12 años de edad y otro a los 15. Los otros dos casos fueron diagnosticados a los 18 y 26 años, se implantó marcapaso definitivo en ellos 8 y 5 años después respectivamente. En un caso no se implantó marcapaso definitivo; un recién nacido con solo un año de seguimiento. Al dar a luz, el 60 % de las madres estaban libres de enfermedad reumática y en conjunto todas tuvieron 19 hijos, ninguno de ellos presentó manifestaciones de LN. CONCLUSIONES: El BAVCC es raro y frecuentemente está asociado a una enfermedad autoinmune materna, prácticamente todos requerirán de marcapaso definitivo en alguna época de su vida.

Unmasking the invisible enemy: A case report of metagenomics-guided diagnosis and treatment of neonatal septic meningitis caused by Corynebacterium aurimucosum in a preterm infant with neonatal lupus erythematosus.

RATIONALE: Neonatal septic meningitis is a serious condition that can be caused by various pathogens, including Corynebacterium aurimucosum, a rare and opportunistic bacterium. We reports a case of infectious meningitis in a premature infant with neonatal lupus erythematosus caused by C aurimucosum. The purpose of this study is to explore the occurrence of meningitis caused by C aurimucosum in preterm infants with neonatal lupus erythematosus. We found that early diagnosis and treatment are crucial for this type of meningitis, especially for infants with impaired immunity or mothers receiving immunosuppressive therapy. This bacterium is rare in clinical practice, but it needs to be taken seriously. PATIENT CONCERNS: The infant was born to a mother with systemic lupus erythematosus who had a history of long-term immunosuppressive therapy. The infant presented with preterm birth, purplish-red skin, fever, and widespread scarlet dermatitis. He also had positive anti-Ro/SSA and anti-La/SSB antibodies. DIAGNOSIS: The infant was diagnosed with neonatal lupus erythematosus based on clinical and serological features. A lumbar puncture revealed septic meningitis with high levels of total nucleated cells, protein, and Pan's test in the CSF. The macrogenic examination identified C aurimucosum as the causative agent. The culture of the mother's vaginal secretion also revealed the same bacterium. INTERVENTIONS: The infant was treated with anti-infective therapy with ceftriaxone, ampicillin, vancomycin, and meropenem. He also received prednisone and gammaglobulin infusion for neonatal lupus erythematosus. OUTCOMES: The infant's temperature returned to normal, and his general condition and responsiveness improved. The CSF cytology and biochemistry normalized, and the culture was negative. The cranial MRI examination showed no abnormalities. The red rash disappeared, and the follow-ups after discharge revealed no complications. LESSONS: This case highlights the importance of early diagnosis and treatment of neonatal septic meningitis caused by C aurimucosum, especially in infants with immunocompromised conditions or maternal history of immunosuppressive therapy. C aurimucosum should not be overlooked as a potential pathogen in neonatal septic meningitis.

Neonatal lupus erythematosus as a rare trigger of gastrointestinal involvement in neonates.

Cutaneous and cardiac involvement in neonatal lupus erythematosus (NLE) has been extensively studied; however, gastrointestinal system involvement (GSI) remains unexplored. This study aimed to investigate the clinical features of GSI in patients with NLE with a particular focus on feeding intolerance (FI) and diarrhea. We conducted a retrospective analysis of the clinical data of patients diagnosed with NLE at the Children's Hospital of Soochow University between 2011 and 2022. In this study, of 39 patients diagnosed with NLE, 27 presented with GSI. 9 patients who presented with FI or diarrhea as the primary manifestation were positive for anti-SSA antibody, and 5 were dual positive for anti-SSA and anti-SSB antibodies. Among the mothers of the NLE patients with GSI, 18 had systemic lupus erythematosus, 3 had Sjogren's syndrome, 2 had mixed connective tissue disease, and one each had autoantibody abnormalities and photosensitivity symptoms; 4 mothers denied having any autoimmune disease. In this study, 69.23% of patients with NLE exhibited GSI, which was linked to hypocomplementemia and anti-SSA antibodies. Thus, clinicians should remain vigilant for NLE in neonates, particularly when accompanied with rash and other organ dysfunction and when the high-risk factors of FI and diarrhea have been excluded.

Preliminary Evaluation of in vivo Reflectance Confocal Microscopy Features of Neonatal Lupus Erythematosus.

INTRODUCTION: Neonatal lupus erythematosus (NLE) is a rare autoimmune disease, which needs to be distinguished from eczema, congenital syphilis, and tinea corporis in newborns. Reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool, which has been used to evaluate several inflammatory skin conditions. The aim of this study was to describe the RCM characteristics of NLE. METHODS: Eleven NLE patients were included in the study, and all patients were evaluated clinically with RCM. We also evaluated RCM images from 11 eczema patients as controls. RESULTS: Some major key diagnostic features of NLE can be observed by RCM: an enlarged honeycomb pattern (9/11, 81.8%), round-to-oval cyst-like structures were present (6/11, 54.5%), the normal ring-like structures were totally or partially obliterated (11/11, 100%) at the level of the dermo-epidermal junction, medium refractivity collagen fibers that were disorganized (10/11, 90.9%), numerous high refractivity round cells (11/11, 100%) in the dermis. CONCLUSION: RCM allows the visualization of major key diagnostic features of NLE and serves as a complementary diagnostic tool for NLE.

High-risk groups of neonatal lupus erythematosus in term infants: a birth cohort study.

This study aims to analyze the clinical characteristics and risk factors of high-risk groups of neonatal lupus erythematosus (NLE) in term infants. High-risk groups of NLE infants whose mothers were positive for anti-SSA, anti-SSB or anti-U1RNP antibodies during pregnancy were enrolled. They were born between February 2013 and February 2020, with a gestational age not less than 37 weeks. We analyzed their clinical data from birth to 24 months after birth. A total of 105 patients in the NLE high-risk group were included. Among them, 30 patients were diagnosed with NLE (NLE group), and 75 patients were not (non-NLE group). The affected systems of the NLE group included the dermal (13.3%), hepatic (76.0%), and hematological systems (43.3%). Hepatic involvement, anemia and thrombocytopenia did not emerge until 60 days, 41 days and 22 days after birth, respectively, in some cases. Systemic involvement could be cured within 3 to 12 months after birth. The clearance time of specific autoantibodies was 12 months after birth. There was no significant difference in the clinical characteristics of babies and their mothers between the two groups, neither in the positive rate nor in the clearance time of specific autoantibodies. CONCLUSION: After standardized prenatal health care, there is still a high risk of dermal, hepatic, or hematological system involvement for high-risk groups of NLE. There are no specific indicators for the prediction of whether babies will develop NLE. All of these patients need to be followed up closely within one year after birth. WHAT IS KNOWN: • Neonatal lupus erythematosus (NLEs) can affect the cardiac, dermal, hepatic, and hematological systems of infants. WHAT IS NEW: • After standardized prenatal health care employing good multidepartment cooperation in our center, no neonates had cardiac block in this study. However, dermal, hepatic, and hematological system involvement of NLE can still gradually appear (as long as 60 days after birth in some cases) during follow-up, and some of these conditions are serious and require timely and active intervention. No single factor has been found to predict whether offspring at high-risk of NLE whose mothers are positive for anti-SSA, SSB and/or RNP will develop NLE.

[Maternal lupus diagnosed through skin lesions of a newborn]. / Een pasgeborene met huidafwijkingen.

Directly after birth a newborn was found to have distinctive skin lesions on her face. The lesions were suspicious for neonatal lupus. Her asymptomatic mother tested positive for anti-SSA/Ro and anti-SSB/La antibodies. The newborn had no complications of neonatal lupus (e.g. atrioventricular block, anemia, neutropenia, or liver enzyme elevation) and the lesions faded within two weeks.

Gut dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus.

Anti-SSA/Ro antibodies, while strongly linked to fetal cardiac injury and neonatal rash, can associate with a spectrum of disease in the mother, ranging from completely asymptomatic to overt Systemic Lupus Erythematosus (SLE) or Sjögren's Syndrome (SS). This study was initiated to test the hypothesis that the microbiome, influenced in part by genetics, contributes to disease state. The stool microbiome of healthy controls (HC) was compared to that of anti-SSA/Ro positive women whose children had neonatal lupus. At the time of sampling, these women were either asymptomatic (Asym), had minor rheumatic symptoms or signs considered as an undifferentiated autoimmune syndrome (UAS), or were diagnosed with SLE or SS. Differences in microbial relative abundances among these three groups were tested assuming an ordering in clinical severity (HC

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

OBJECTIVE: Neonatal 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 with anti-Ro/SSA antibodies is well established, but a recurrence rate of only 12%-16% despite persisting maternal autoantibodies suggests that additional factors are required for CHB development. Here, we identify fetal genetic variants conferring risk of CHB and elucidate their effects on cardiac function. METHODS: A genome-wide association study was performed in families with at least one case of CHB. Gene expression was analysed by microarrays, RNA sequencing and PCR and protein expression by western blot, immunohistochemistry, immunofluorescence and flow cytometry. Calcium regulation and connectivity were analysed in primary cardiomyocytes and cells induced from pleuripotent stem cells. Fetal heart performance was analysed by Doppler/echocardiography. RESULTS: We identified DNAJC6 as a novel fetal susceptibility gene, with decreased cardiac expression of DNAJC6 associated with the disease risk genotype. We further demonstrate that fetal cardiomyocytes deficient in auxilin, the protein encoded by DNAJC6, have abnormal connectivity and Ca2+ homoeostasis in culture, as well as decreased cell surface expression of the Cav1.3 calcium channel. Doppler echocardiography of auxilin-deficient fetal mice revealed cardiac NLE abnormalities in utero, including abnormal heart rhythm with atrial and ventricular ectopias, as well as a prolonged atrioventricular time intervals. CONCLUSIONS: Our study identifies auxilin as the first genetic susceptibility factor in NLE modulating cardiac function, opening new avenues for the development of screening and therapeutic strategies in CHB.

Lupus Pneumonitis: Case Report of a Rare Manifestation of Neonatal Lupus.

Neonatal lupus is a rare entity, secondary to placental transfer of antibodies from mothers with immune-mediated conditions. While pulmonary involvement is common in lupus, its incidence in neonates is extremely rare, with very few cases being reported in the literature. The authors report a case of a neonate whose mother was diagnosed with systemic lupus erythematosus, with a prenatal diagnosis of third-degree atrioventricular block. While initially admitted in the neonatal intensive care unit with no need for organ support, he presented progressive respiratory failure, initially attributed to sepsis. Favorable clinical progression after pacemaker placement allowed ventilatory weaning, but respiratory failure was again apparent. Chest computer tomography revealed areas of ground-glass lesions, raising the suspicion for lupus pneumonitis. He was started on immunoglobulin and corticosteroids, with clinical improvement. The authors consider this case to be relevant due to the rarity of acute lupus pneumonitis in neonates, alerting that it must be considered a differential diagnosis in neonates with prolonged ventilator dependency.

Prenatal predisposing factors associated with neonatal lupus erythematosus.

OBJECTIVES: To identify the prenatal predisposing factors related to neonatal lupus erythematosus (NLE). MATERIALS AND METHODS: A retrospective case-control study was made of 131 pregnant women with positive anti-Ro or anti-La autoantibodies and known neonatal outcomes between January 2002 and December 2019 at Siriraj Hospital, Bangkok, Thailand. There were 101 unaffected neonates and 30 NLE cases confirmed postnatally. Demographic and clinical data of the mothers and neonates with and without NLE were statistically compared. RESULTS: NLE was diagnosed in 30 out of 131 cases. A multivariate analysis identified the following significant factors for NLE: maternal anti-La antibodies (odds ratio (OR), 3.591; p = 0.030); and maternal treatment with either hydroxychloroquine (OR, 0.082; p = 0.001) or prednisolone (OR, 0.136; p = 0.017). Of the significant variables examined in the multivariate analysis models, high levels of maternal anti-La antibodies were found to be the strongest predictor of noncardiac NLE (OR, 4.558; p = 0.032), while a female baby was significantly higher in pregnancies complicated by cardiac NLE (OR, 5.374; p = 0.046). Hydroxychloroquine still provided a protective effect for both cardiac and noncardiac NLE (p = 0.039 and 0.032, respectively). CONCLUSIONS: The maternal anti-La antibodies were a beneficial predictor for NLE, especially as their high titers were influentially associated with noncardiac features. A female fetus seemed to present an increased risk for developing a congenital heart block. Nevertheless, the treatment with hydroxychloroquine during the pregnancies demonstrated a potentially protective factor against both cardiac and noncardiac manifestations.

Clinical Features, Autoantibodies, and Outcome of Neonatal Lupus Erythematosus.

Objectives: To explore the clinical features, autoantibodies, and outcome of neonatal lupus erythematosus (NLE). Methods: We retrospectively reviewed all NLE cases from January 2012 to May 2019 that occurred in our department. Results: Cutaneous, cardiac, hematologic, and hepatobiliary manifestations were found in 36.7%, 56.7%, 56.7%, and 30.0% of cases, respectively. The presence of anti-SSA antibodies was correlated with cardiac presentation (p = .026) and the presence of anti-SSB antibodies was associated with cutaneous lesions (p = .015). During the follow-up, one patient with a third-degree atrioventricular block died, and a third-degree AV block persists in a child without a pacemaker at 4-years of age. No other manifestations of NLE were observed after the age of 12 months. Conclusions: Anti-SSA and anti-SSB are associated with cardiac and cutaneous manifestations in NLE. Most children with NLE have excellent outcomes with symptom resolution by one year. Complete congenital heart block may persist.

Neonatal lupus: a clinical challenge.

Neonatal lupus is an uncommon entity. The main manifestations are cutaneous and cardiac. It is caused by transplacental passage of maternal antibodies (anti-Ro/SSA or anti-La/SSB), and the diagnosis is made by its detection in the mother or child. The authors present a case of a 4-month-old female infant, with a cutaneous eruption since she was 2 months old. She had no relevant personal or family history. Analytically she had an increase in liver enzymes. The histological aspect of the skin biopsy led to an autoimmunity study on the mother and infant, both of which had positive anti-Ro/SSA antibodies, confirming the diagnosis of neonatal lupus. Cardiological study was normal. The skin lesions resolved during the first year of life. Skin lesions are the most frequent non-cardiac clinical manifestation of neonatal lupus, and they are self-limited. When there is no family history, nor cardiac involvement, the diagnosis can be challenging.

Complete heart block in neonatal lupus: a forgotten cause of fetal bradycardia.

The most common cause of congenital heart block (CHB) is neonatal lupus, an acquired autoimmune disease caused by transplacental transfer of maternal antibodies to the fetus. A full-term female neonate was admitted to neonatal intensive care unit for severe bradycardia with stable haemodynamics. The mother, showing no clinical symptoms or any particular history, was transferred to our tertiary centre for profound fetal bradycardia. At birth, the infant's ECG showed a third-degree atrioventricular block and echocardiography was normal. Cardiac neonatal lupus was confirmed with positive maternal anti-Ro antibodies. Under close monitoring, the infant tolerated the bradycardia well (median 67 beats per minute (bpm)) and was discharged on day 6 of life. There was no indication for pacemaker, but she would be on regular follow-up with a paediatric cardiologist. This article holds an important insight as it is the first confirmed case of autoimmune CHB in Cambodia in which the mother's antibody was found only after diagnosis on the neonate.

An Overview of Neonatal Lupus with Anti-Ro Characteristics.

Neonatal lupus erythematosus (NLE) is a syndrome of clinical symptoms observed in neonates born to mothers with antibodies to soluble antigens of the cell nucleus. The main factors contributing to the pathogenesis of this disease are anti-Sjögren Syndrome A (anti-SS-A) antibodies, known as anti-Ro, and anti-Sjögren Syndrome B (anti-SS-B) antibodies, known as anti-La. Recent publications have also shown the significant role of anti-ribonucleoprotein antibodies (anti-RNP). Seropositive mothers may have a diagnosed rheumatic disease or they can be asymptomatic without diagnosis at the time of childbirth. These antibodies, after crossing the placenta, may trigger a cascade of inflammatory reactions. The symptoms of NLE can be divided into reversible symptoms, which concern skin, hematological, and hepatological changes, but 2% of children develop irreversible symptoms, which include disturbances of the cardiac stimulatory and conduction system. Preconceptive care and pharmacological prophylaxis of NLE in the case of mothers from the risk group are important, as well as the monitoring of the clinical condition of the mother and fetus throughout pregnancy and the neonatal period. The aim of this manuscript is to summarize the previous literature and current state of knowledge about neonatal lupus and to discuss the role of anti-Ro in the inflammatory process.