Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies

Quaio, Caio Robledo; Carvalho, Jozélio Freire de; Silva, Clovis A. da; Bueno, Cleonice; Brasil, Amanda Salem; Pereira, Alexandre C.; Jorge, Alexander A L; Malaquias, Alexsandra C.; Kim, Chong; Bertola, Débora Romeo

doi:10.1002/ajmg.a.35290

Cited by 81 publications

(70 citation statements)

References 32 publications

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“…64 Because autoimmune thyroiditis is common in the general population, measurements of thyroid function are recommended at diagnosis. Only a few instances of hypothyroidism have been documented in CFC, 29 so follow-up thyroid testing can be decided by an endocrinologist.…”

Section: State-of-the-art Review Article Endocrine Issuesmentioning

confidence: 99%

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

et al. 2014

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Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

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Section: State-of-the-art Review Article Endocrine Issuesmentioning

confidence: 99%

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

et al. 2014

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“…In a series of 42 patients with RASopathies, 52% were shown to have autoantibodies against various tissues. 23 Other investigators suggested a predisposition to the development of systemic lupus erythematosus in NS. 24 …”

Section: Ras and The Ras/mitogen-activated Protein Kinase Signaling Cmentioning

confidence: 99%

RAS diseases in children

Niemeyer

2014

Haematologica

127

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REVIEW ARTICLES 1653 IntroductionDiscoveries made about 50 years ago revealed the transforming power of the Harvey and Kirsten murine sarcoma retroviruses by a set of genes named RAS genes for their role in forming rat sarcomas. Subsequently, the contribution of RAS genes to cancer pathogenesis has been studied extensively. While the somatic dysregulation of RAS is a primary driver of cancer, there is a class of developmental disorders caused by germline mutations (as opposed to the somatic mutations found in cancer) in genes that encode components of the RAS signaling pathway. This chapter summarizes hematologic disturbances and cancer predisposition of these genetic disorders named "RASopathies". It will focus on juvenile myelomonocytic leukemia (JMML), an infant leukemia with initiating germline and somatic mutations in genes of the RAS signal transduction pathway. RAS and the RAS/mitogen-activated protein kinase signaling cascadeRAS turned out to be an essential cellular hub for a wide variety of signaling pathways including the three human RAS genes, KRAS, NRAS and HRAS (reviewed by Stephen et al. 1). RAS proteins act as molecular switches by cycling between an active guanosine triphospate (GTP)-bound (RAS-GTP) and an inactive guanosine diphosphate (GDP)-bound (RAS-GDP) conformation (Figure 1).2 RAS-GTP concentrations are tightly regulated by the competitive action of guanosin exchange factors (GEFs) and GTPase activating proteins (GAPs).RAS is activated by extracellular stimuli such as growth factor binding to receptor tyrosine kinases (RTKs) followed by RTK autophosphorylation and the creation of docking sites for adaptor molecules (e.g. GRB2). These molecules recruit and activate GEFs (e.g. SOS1) which displace GDP from RAS allowing RAS to bind to GTP. RAS-GTP binds to and activates a large number of effector pathways. The RAS-mediated mitogen-activated kinase (MAPK) pathway is one of several important downstream cascades. Activated RAS binds to RAF (RAF1, also known as CRAF, BRAF), the first MAPK of the signaling cascade. RAF phosphorylates MEK1 and/or MEK2, which in turn activate ERK1 and/or ERK2. Active ERKs serve as regulators of a large number of downstream processes both in the cytosol and nucleus.

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“…Additionally, increased serum level of mtDNA was detected in patients diagnosed with various neurodegenerative disorders, such as autism, Parkinson disease and multiple sclerosis [10,11,12]. Several authors have suggested that mtDNA can act as trigger points for the development of autoimmune disorders as well [10,13]. Although immune reactivity towards nucleic acids is well established, it remains to determine which type of nucleic acids are more immunogenic in SLE.…”

Section: Introductionmentioning

confidence: 99%

Differential Immuno-Reactivity to Genomic DNA, RNA and Mitochondrial DNA is Associated with Auto-Immunity

Ivanova

Khaiboullina

Черенкова

et al. 2014

Cell Physiol Biochem

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Background: Circulating auto-reactive antibodies are hallmark features of auto-immune diseases, however little is known with respect to the specificity of such bio-markers. In the present study, we investigated the specificity of anti-nucleic acid antibodies in the blood of subjects with systemic lupus erythematosus (SLE) and healthy controls. Methods: Sera from 12 SLE cases and 8 controls were evaluated for immuno-reactivity to purified RNA, DNA and mitochondrial DNA (mtDNA) by enzyme-linked immuno-sorbent assay (ELISA). Results: As expected, immuno-reactivity to total nucleic acids was significantly higher in subjects with SLE when compared to healthy controls, however a clear distinction was observed among the various nucleic acid sub-types, with sera from SLE subjects displaying the greatest immuno-reactivity to RNA followed by mtDNA and then total DNA. Conclusion: The identification of auto-reactive antibodies can serve as highly sensitive biomarkers, although their specificity may not always allow diagnostic certainty. The knowledge that auto-antibodies in subjects with SLE display differential immuno-reactivity may help to improve existing diagnostics and may lead to a better understanding of the pathogenesis of auto-immune disorders.

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Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies

Cited by 81 publications

References 32 publications

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

RAS diseases in children

Differential Immuno-Reactivity to Genomic DNA, RNA and Mitochondrial DNA is Associated with Auto-Immunity

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