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Sharmaine Kachmar
The Lupus Foundation of America has several grant programs for investigators at every stage of their career in lupus research. Our grant programs are designed to drive novel approaches in lupus research across a variety of fields, including basic science and translational and clinical research.
The goal of this program is to foster an interest among students in the areas of basic, clinical, translational, epidemiological, or behavioral research relevant to lupus. Students must work under the sponsorship and supervision of an established, tenure-track principal investigator who directs a laboratory dedicated at least in part to the investigation of lupus at an academic, medical, or research institution.
Lupus Foundation of America has partnered with Lupus Canada for the Catalyst Grant. The Catalyst Grant is intended to help kick-start a new project or research idea focused on discoid or systemic lupus erythematosus (SLE). This grant provides support to Canadian investigators to initiate new research ideas and projects and is intended to complement rather than compete with traditional sources of funding such as the Canadian Institutes for Health Research (CIHR).
Each year, our Medical-Scientific Advisory Council chooses research priorities and creates topic-focused opportunities for investigators to apply for funding. This grant program prioritizes the most urgent and unmet needs in lupus research.
The Lupus Foundation of America established in 2005 the Evelyn V. Hess, MD, MACP, MACR, Award to be given annually to a clinical or basic researcher whose body of work has significantly advanced understanding of the pathophysiology, etiology, epidemiology, diagnosis or treatment of lupus. This award was created to honor Dr. Hess' outstanding contributions to lupus research over the course of her long career.
The Lupus Foundation of America established in 2009 the Mary Betty Stevens, MD, Young Investigator Prize to be given annually in recognition of the exceptional achievements of an investigator in the early part of his or her independent career in lupus research. This award was created to memorialize Dr. Stevens who made exceptional contributions to lupus research starting from early on in her career.
Neonatal lupus erythematosus is an autoimmune disease that takes place due to the passive maternal transfer of autoantibodies of Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB) to the fetus. The incidence of neonatal lupus erythematosus approximates to 2% in offspring of mothers with autoantibodies of Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB) with an 18 to 20 percent recurrence rate in subsequent pregnancies. Neonatal lupus erythematosus causes 80 to 95 percent of the cases of severe atrioventricular block in the neonatal period (younger than 28 days of life); after this period it is a less frequent cause of AV block (5 percent of cases). This activity describes the monitoring, evaluation, diagnosis, and management of neonatal lupus erythematosus and stresses the role of team-based interprofessional care for affected patients and their families.
Objectives:
- Identify the etiology of neonatal lupus erythematosus.Describe the evaluation of neonatal lupus erythematosus.Review the treatment and management options available for neonatal lupus erythematosus.Summarize interprofessional team strategies for improving care coordination and communication to advance prevention and treatment of neonatal lupus erythematosus and improve outcomes.
Neonatal lupus erythematosus belongs to a group of medical conditions in which immunoglobulin G is transported across the placenta to the fetal circulation and directed against auto-antigens causing clinical manifestations in the neonate, other examples within this group are antiphospholipid antibody syndrome, Graves-Basedow disease, immune thrombocytopenic purpura, myasthenia gravis, Sjogren syndrome, systemic lupus erythematosus, and neonatal autoimmune blistering disease. Neonatal lupus erythematosus was first described by Bridge and Foley in 1954 after they observed the transmission of maternal lupus erythematosus factor to newborn infants. The same year, a case of lupus rash in a 6-week old infant was reported, a product of a mother that months later was diagnosed with systemic lupus erythematosus. In 1957, a case of an infant with congenital heart disease, whom mother had systemic lupus erythematosus was disclosed. Years later after these first cases were reported, infants with neonatal lupus erythematosus were associated with transient cytopenia and abnormal elevation of aminotransferase.[1][2][3]
Neonatal lupus erythematosus is an autoimmune disease that takes place due to the passive maternal transfer of autoantibodies of Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB) to the fetus. Autoantibodies against antigen type A recognize 2 cellular proteins, Ro52/52kD (localized in the nucleus and cytoplasm) and Ro60/60kD (localized in the nucleus and nucleolus). Autoantibodies against antigen type B target a 47kD protein localized between the nucleus and the cytoplasm. So far there is no specific epitope responsible for neonatal lupus erythematosus, but some animal models have suggested a greater role of anti Ro52.[1][3]
The incidence of neonatal lupus erythematosus approximates to 2% in offspring of mothers with autoantibodies of Sjogren syndrome autoantigen type A (Ro/SSA) or B (La/SSB) with an 18% to 20% recurrence rate in the following pregnancies. It affects equally males and females, and less than 5% of infants with this condition will develop systemic lupus erythematosus in late adolescence or early adulthood. Neonatal lupus erythematosus causes 80% to 95% of the cases of severe atrioventricular block in the neonatal period (younger than 28 days of life), after this period it is a less frequent cause of AV block (5% of the cases). Presentation of cutaneous manifestations ranges between 7% to 16% of mothers with positive autoantibodies type A (Ro/SSA) or B (La/SSB). These autoantibodies are present in 0.1% to 1.5% of healthy pregnant women, 90% of patients with Sjogren, 20% to 30% with systemic lupus erythematosus and 3% with rheumatoid arthritis. Approximately 25% of the mothers of neonates with neonatal lupus are asymptomatic at the time of delivery, of which 50% will become symptomatic within three years. Another 25% have an undifferentiated autoimmune syndrome, 20% Sjogren syndrome, 15% systemic lupus erythematosus, 15% systemic lupus erythematosus associated with Sjogren syndrome and 1% Rheumatoid arthritis.[1][2][4]
One mechanism that have been proposed to explain atrioventricular heart block postulate that from the 18 to the 26 weeks of pregnancy auto-antigens type A or B translocate to the cardiomyocyte surface after which maternal autoantibodies bind to the fetal cardiac conduction tissue triggering atrioventricular node fibrosis. Another mechanism that has been postulated is based on mimicry, linking a cross-reaction between L- and T-type calcium channels and autoantibodies that subsequently cause an imbalance with calcium homeostasis, crucial for the propagation of the action potential and conduction in the AV and SA node. AV heart block is often seen if the mother has higher autoantibodies titers. Nevertheless, there is overlapping between affected and unaffected cases that a high titer alone is not indicative of heart involvement. Another maternal factor that has been linked with neonatal lupus cutaneous manifestations is anti-U1 RNP (small nuclear ribonucleoprotein-associated with U1 spliceosomal RNA) antibodies.[1][2][3]
Neonatal lupus erythematosus presents with reversible manifestations including cutaneous lesions in 40% of the cases, 35% hepatic dysfunction and 35% hematological abnormalities; a 25% of neonates present with irreversible cardiac arrhythmias, the most distinctive and dangerous feature.
Lesions resemble those seen in children and adolescents with systemic lupus erythematosus. Eruptions are often misdiagnosed as birth trauma, skin infection or eczema, especially if the mother is asymptomatic. 80% of the lesions are not clear at birth developing during the first month of life in only 20% of the affected newborns. Neonates present with photosensitivity usually within the first 2 days of sun exposure in 90% of the cases. Cutaneous lesions characterized by a superficial inflammatory coalescent rash with raised active margins, described as macular annular or elliptic erythema that involves the head (with or without the scalp or neck) in 95%, scalp in 60%, trunk (with or without groin) in 25%, extremities in 25% and can involve the whole body in 10% of the cases. Sometimes it can manifest as papular or plaque-like lesions, and 30% can present with a central clearing lesion or a fine scale. The classic rash remits within 4 months of life in 50% of the cases, 80% within 7 months and 100% within a year. Twenty percent of neonates can present with persisting skin rash characterized by telangiectasia, hyperpigmented skin areas, and atrophy. On histological examination, granular depositions of immunoglobulin G at the dermo-epidermal junction and vacuolar alteration at the interface and adnexal structures can be observed.
These manifestations are transient and rarely present as an isolated sign. Regarding the hematological aspect, newborns with neonatal lupus syndrome can present with anemia, neutropenia or thrombocytopenia. In 20% of the cases, aplastic anemia has been reported. There is an asymptomatic elevation of aminotransferases, cholestasis, or hepatomegaly/splenomegaly in 15% to 25% of the cases.
Newborns with neonatal lupus erythematosus usually have a structurally normal heart. The classic and distinctive cardiac manifestation is a congenital atrioventricular block that can present as first, second, and especially third-degree AV block. Commonly presents between 18 to 24 weeks of gestation. Other cardiac manifestations include sinus bradycardia, QT-interval prolongation, cardiomyopathy, congestive heart failure, myocarditis and structural or valvular abnormalities (ventricular septal defects, ostium secundum type atrial septal defects, patent foramen ovale, patent ductus arteriosus, pulmonary stenosis, pulmonary valve dysplasia, fusion of the chordae tendineae of the tricuspid valve). Second- and third-degree AV block present in utero with fetal bradycardia, with a ventricular rate between 40 and 80 per minute. Postnatally the heart rate is found to be less than 100 per minute, rarely associated with signs of congestive heart failure (diaphoresis, pallor, peripheral edema, prominent jugular veins and crackles on auscultation of the lungs). On cardiac auscultation, there can be an appreciation of nonspecific signs such as intermittent gallops, variability with the intensity of the first heart sound, intermittent cannon waves, and murmurs. Five percent to 10% of infants present with a severe AV block that precipitates myocardial dysfunction due to endocardial fibroelastosis and myocardial fibrosis, associated with right ventricular pacing and subsequent ventricular asynchrony and dysfunction.[1][2]
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