Search for mutations of the interferon-induced transmembrane protein 5 (IFITM5) gene in patients with osteogenesis imperfecta

2019 ◽  
pp. 21-29
Author(s):  
А.Р. Зарипова ◽  
Л.Р. Нургалиева ◽  
А.В. Тюрин ◽  
И.Р. Минниахметов ◽  
Р.И. Хусаинова
Keyword(s):  
Osteogenesis Imperfecta ◽  
De Novo ◽  
Transmembrane Protein ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Heterozygous Mutation ◽  
Type I ◽  
New Genes ◽  
Wide Range ◽  
Type V

Проведено исследование гена интерферон индуцированного трансмембранного белка 5 (IFITM5) у 99 пациентов с несовершенным остеогенезом (НО) из 86 неродственных семей. НО - клинически и генетически гетерогенное наследственное заболевание соединительной ткани, основное клиническое проявление которого - множественные переломы, начиная с неонатального периода жизни, зачастую приводящие к инвалидизации с детского возраста. К основным клиническим признакам НО относятся голубые склеры, потеря слуха, аномалия дентина, повышенная ломкость костей, нарушения роста и осанки с развитием характерных инвалидизирующих деформаций костей и сопутствующих проблем, включающих дыхательные, неврологические, сердечные, почечные нарушения. НО встречается как у мужчин, так и у женщин. До сих пор не определена степень генетической гетерогенности заболевания. На сегодняшний день известно 20 генов, вовлеченных в патогенез НО, и исследователи разных стран продолжают искать новые гены. В последнее десятилетие стало известно, что аутосомно-рецессивные, аутосомно-доминантные и Х-сцепленные мутации в широком спектре генов, кодирующих белки, которые участвуют в синтезе коллагена I типа, его процессинге, секреции и посттрансляционной модификации, а также в белках, которые регулируют дифференцировку и активность костеобразующих клеток, вызывают НО. Мутации в гене IFITM5, также называемом BRIL (bone-restricted IFITM-like protein), участвующем в формировании остеобластов, приводят к развитию НО типа V. До 5% пациентов имеют НО типа V, который характеризуется образованием гиперпластического каллуса после переломов, кальцификацией межкостной мембраны предплечья и сетчатым рисунком ламелирования, наблюдаемого при гистологическом исследовании кости. В 2012 г. гетерозиготная мутация (c.-14C> T) в 5’-нетранслируемой области (UTR) гена IFITM5 была идентифицирована как основная причина НО V типа. В представленной работе проведен анализ гена IFITM5 и идентифицирована мутация c.-14C>T, возникшая de novo, у одного пациента с НО, которому впоследствии был установлен V тип заболевания. Также выявлены три известных полиморфных варианта: rs57285449; c.80G>C (p.Gly27Ala) и rs2293745; c.187-45C>T и rs755971385 c.279G>A (p.Thr93=) и один ранее не описанный вариант: c.128G>A (p.Ser43Asn) AGC>AAC (S/D), которые не являются патогенными. В статье уделяется внимание особенностям клинических проявлений НО V типа и рекомендуется определение мутации c.-14C>T в гене IFITM5 при подозрении на данную форму заболевания. A study was made of interferon-induced transmembrane protein 5 gene (IFITM5) in 99 patients with osteogenesis imperfecta (OI) from 86 unrelated families and a search for pathogenic gene variants involved in the formation of the disease phenotype. OI is a clinically and genetically heterogeneous hereditary disease of the connective tissue, the main clinical manifestation of which is multiple fractures, starting from the natal period of life, often leading to disability from childhood. The main clinical signs of OI include blue sclera, hearing loss, anomaly of dentin, increased fragility of bones, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, and renal disorders. OI occurs in both men and women. The degree of genetic heterogeneity of the disease has not yet been determined. To date, 20 genes are known to be involved in the pathogenesis of OI, and researchers from different countries continue to search for new genes. In the last decade, it has become known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes encoding proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells cause OI. Mutations in the IFITM5 gene, also called BRIL (bone-restricted IFITM-like protein), involved in the formation of osteoblasts, lead to the development of OI type V. Up to 5% of patients have OI type V, which is characterized by the formation of a hyperplastic callus after fractures, calcification of the interosseous membrane of the forearm, and a mesh lamellar pattern observed during histological examination of the bone. In 2012, a heterozygous mutation (c.-14C> T) in the 5’-untranslated region (UTR) of the IFITM5 gene was identified as the main cause of OI type V. In the present work, the IFITM5 gene was analyzed and the de novo c.-14C> T mutation was identified in one patient with OI who was subsequently diagnosed with type V of the disease. Three known polymorphic variants were also identified: rs57285449; c.80G> C (p.Gly27Ala) and rs2293745; c.187-45C> T and rs755971385 c.279G> A (p.Thr93 =) and one previously undescribed variant: c.128G> A (p.Ser43Asn) AGC> AAC (S / D), which were not pathogenic. The article focuses on the features of the clinical manifestations of OI type V, and it is recommended to determine the c.-14C> T mutation in the IFITM5 gene if this form of the disease is suspected.

scholarly journals Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

2017 ◽  
Vol 54 (6) ◽  
pp. 371-380 ◽  
Author(s):  
Ange-Line Bruel ◽  
Brunella Franco ◽  
Yannis Duffourd ◽  
Julien Thevenon ◽  
Laurence Jego ◽  
...  
Keyword(s):  
Transition Zone ◽  
Genetic Disorders ◽  
Intraflagellar Transport ◽  
Heterozygous Mutation ◽  
Type I ◽  
Gene Encoding ◽  
Distinct Subgroup ◽  
Functional Studies ◽  
New Genes ◽  
Wide Range

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in theOFD1gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3,TMEM107,INTU,KIAA0753andIFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42,TMEM138,TMEM231andWDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype.

scholarly journals Apert syndrom: a literature review and own clinical case

2020 ◽  
pp. 55-58
Author(s):  
V.M. Husiev ◽  
◽  
D.S. Khapchenkova ◽  
V.E. Kleban ◽  
◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Clinical Case ◽  
Clinical Symptoms ◽  
Proximal Phalanx ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Apert Syndrome ◽  
Type I ◽  
Hands And Feet ◽  
Type V

Acrocephalosyndactyly (ACS) is a group of multiple malformations, the main clinical manifestations of which are acrocephaly and syndactyly. The most common forms are Apert (type I), Pfeiffer (type V), Setra–Hotzen (type II) syndromes. Apert syndrome is the most explored and common form of all types of ACS and Apert syndrome is estimated to occur in 1 in: 100 000 newborns. The syndrome is inherited in an autosomal dominant manner. If the gene is carried by one of the parents, the risk of having a child with Apert syndrome is 50%. The syndrome genome (FGFR2) is located on the long arm of chromosome 10 at locus 10q26. Apert syndrome occurs due to mutations at this locus, but the children karyotype is not changed. The pathognomonic clinical signs of Apert syndrome are craniofacial dysostosis and symmetrical syndactyly of the hands and feet. Acrocephaly («tower skull») — is a consequence of early synostosis of some sutures of the skull. Orbital hypertelorism and exophthalmos are referred to typical facial changes. Among other abnormalities there are heart and vascular defects (25%), cleft palate, malformations of the gastrointestinal tract and kidneys. The diagnosis is made on the basis of clinical symptoms. No treatment has been developed. Life expectancy is short. Purpose — to present a clinical case of a newborn with Apert syndrome. Clinical case. Apert syndrome was suspected prenatally, confirmed after birth. The newborn girl had the characteristic signs of the above-described pathology: «tower head», hypertelorism, saddle bridge of the nose, closed large fontanelle, phalanges of the first finger were wide, the proximal phalanx was triangular, complete cutaneous syndactyly of the II–IV fingers was observed symmetrical on both upper extremities; on the lower extremities — thickening of the proximal phalanges of the big toes, complete cutaneous syndactyly of the II–IV toes. Conclusions. The article describes a clinical case of a child with Apert syndrome. Prenatal diagnosis takes one of the leading places in confirming genetic abnormalities, determining the prognosis for life. Genetic counseling for parents is necessary and important at all stages of pregnancy planning. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Apert syndrome, children, prenatal diagnosis.

scholarly journals New Genes in Bone Development: What's New in Osteogenesis Imperfecta

2013 ◽  
Vol 98 (8) ◽  
pp. 3095-3103 ◽  
Author(s):  
Joan C. Marini ◽  
Angela R. Blissett
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Bone Development ◽  
Clinical Manifestations ◽  
Autosomal Recessive Inheritance ◽  
Bone Dysplasia ◽  
Protein Product ◽  
Type I ◽  
Related Condition ◽  
New Genes

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and deformity and growth deficiency. Most cases of OI (classical types) have autosomal dominant inheritance and are caused by mutations in the type I collagen genes. During the past several years, a number of noncollagenous genes whose protein products interact with collagen have been identified as the cause(s) of rare forms of OI. This has led to a paradigm shift for OI as a collagen-related condition. The majority of the non-classical OI types have autosomal recessive inheritance and null mutations in their respective genes. The exception is a unique dominant defect in IFITM5, which encodes Bril and leads to hypertrophic callus and interosseous membrane ossification. Three recessive OI types arise from defects in any of the components of the collagen prolyl 3-hydroxylation complex (CRTAP, P3H1, CyPB), which modifies the collagen α1(I)Pro986 residue. Complex dysfunction leads to delayed folding of the procollagen triple helix and increased helical modification. Next, defects in collagen chaperones, HSP47 and FKBP65, lead to improper procollagen folding and deficient collagen cross-linking in matrix, respectively. A form of OI with a mineralization defect is caused by mutations in SERPINF1, whose protein product, PEDF, is a well-known antiangiogenesis factor. Defects in the C-propeptide cleavage enzyme, BMP1, also cause recessive OI. Additional genes, including SP7 and TMEM38B, have been implicated in recessive OI but are as yet unclassified. Elucidating the mechanistic pathways common to dominant and recessive OI may lead to novel therapeutic approaches to improve clinical manifestations.

scholarly journals Osteogênese Imperfeita em cão jovem da raça pinscher

2018 ◽  
Vol 46 ◽  
pp. 5
Author(s):  
Paula Priscila Correa Costa ◽  
Juliana Custódio ◽  
Fernanda Sayuri Ebina ◽  
Liliane Lima Da Silva ◽  
Pedro Ernesto Da Cunha ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Clinical Signs ◽  
Corneal Opacity ◽  
Type I ◽  
Osteogenesis Imperfecta Type ◽  
Multiple Fractures ◽  
Triangular Face ◽  
Type Iii ◽  
Wide Range

Background: Osteogenesis imperfecta is a severe genetic disease rarely described in veterinary medicine. This multisystemic condition is caused by a defect in the production and metabolization of collagen, which implicates in bone fragility. This disease has been described in cattle, sheep, domestic felines, mouse and dogs of different breeds, including collie, golden retriever, beagle, dachshund and chow chow. Animals affected by this condition present multiple fractures without previous occurrence of trauma. Therefore, this report aimed to describe a case of osteogenesis imperfecta type III in a miniature pinscher dog.Case: A 1-year-old male miniature pinscher dog, was admitted for clinical evaluation in Fortaleza, Brazil, with a history of spontaneous fractures without known causes. This animal was maintained indoors, fed on dry feed and presented recurrent events of claudication and pain. In the physical examination, the individual walked solely with the forelimbs, avoiding the use of the hind limbs and presented pain behavior. Bulging of the skull was observed laterally, which promoted a triangular appearance of head and face. Fontanelles were soft, and the eyes presented blueish sclera and corneal opacity. Teeth were small, translucid, fragile and deformed. Radiography images revealed bulging of the calvaria and persistent fontanelles with open cranial sutures. In addition, cranial convolutions were less clear, which was compatible with hydrocephalus. Dental roots were narrow, short and presented partial pulp obliteration. The radiographic contrast of the dentin was low with a reduction of periapical radiolucency. Bone radiopacity was low in the bones of the abdomen and pelvis, in addition to femur. Metaphysis of the right tibia was enlarged and angular. Multiple fractures were identified in the pelvis with the formation of opaque bony calluses and bone marrow sclerosis. Physiological parameters and blood test results were unaltered. After the diagnosis of osteogenesis imperfecta type III, treatment was performed with meloxicam 0.1 mg/kg, SID, VO) and tramadol (2 mg/kg, TID, VO) until pain was controlled. When the patient was stable, the treatment was halted until the next event of fractures followed by pain.Discussion: Type I collagen is considered the most abundant protein in connective tissue, accounting for 95% of the various types of collagen found in bone tissue. In osteogenesis imperfecta, there is a shortage in coding of type I collagen, which prevents this protein from exerting its structural functions properly. In addition, it is subjected to intra and extracellular degradation, affecting cell migration and differentiation and, concomitantly, cell-matrix interaction. Hence, these changes are considered the main pathophysiological factors of osteogenesis imperfecta. There is a wide range of phenotypic presentations in individuals with osteogenesis imperfecta. However, there is a pattern of fractures and features that aid clinically and radiologically in the characterization of the disease and form the basis for case identification and diagnosis. In this case, the diagnosis was concluded primarily considering significant clinical signs, such as: repetitive fractures, triangular face, bulging of the skull, bluish sclera and corneal opacity. Radiographic examinations were used to confirm the diagnosis and to aid in treating the fractures. Although the genetic test provides a better understanding of the disease, it was not performed in this case, as it is routinely unavailable in many treatment centers. In conclusion, we described a case of osteogenesis imperfecta in a miniature pinscher dog.

scholarly journals Modern classification and molecular-genetic aspects of osteogenesis imperfecta

2020 ◽  
Vol 24 (2) ◽  
pp. 219-227
Author(s):  
A. R. Zaripova ◽  
R. I. Khusainova
Keyword(s):  
Osteogenesis Imperfecta ◽  
Bone Tissue ◽  
Autosomal Recessive ◽  
Type I Collagen ◽  
Autosomal Dominant ◽  
Clinical Severity ◽  
Type I ◽  
New Genes ◽  
Wide Range

Osteogenesis imperfecta (imperfect osteogenesis in the Russian literature) is the most common hereditary form of bone fragility, it is a genetically and clinically heterogeneous disease with a wide range of clinical severity, often leading to disability from early childhood. It is based on genetic disorders leading to a violation of the structure of bone tissue, which leads to frequent fractures, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, renal impairment, hearing loss. Osteogenesis imperfecta occurs in both men and women, the disease is inherited in both autosomal dominant and autosomal recessive types, there are sporadic cases of the disease due to de novomutations, as well as X-linked forms. The term “osteogenesis imperfecta” was coined by W. Vrolick in the 1840s. The first classification of the disease was made in 1979 and has been repeatedly reviewed due to the identification of the molecular cause of the disease and the discovery of new mechanisms for the development of osteogenesis imperfecta. In the early 1980s, mutations in two genes of collagen type I (COL1A1and COL1A2) were first associated with an autosomal dominant inheritance type of osteogenesis imperfecta. Since then, 18 more genes have been identified whose products are involved in the formation and mineralization of bone tissue.  The degree of genetic heterogeneity of the disease has not yet been determined, researchers continue to identify new genes involved in its pathogenesis, the number of which has reached 20. In the last decade, it has become  known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes, encoding  proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells, cause imperfect  osteogenesis. A large number of causative genes complicated the classical classification of the disease and, due to new advances in the molecular basis of the disease, the classification of the disease is constantly being improved.  In this review, we systematized and summarized information on the results of studies in the field of clinical and genetic aspects of osteogenesis imperfecta and reflected the current state of the classification criteria for diagnosing the disease.

scholarly journals Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110358
Author(s):  
Lin Qiao ◽  
Yuting Yang ◽  
Dongmei Yue
Keyword(s):  
Genetic Testing ◽  
Early Diagnosis ◽  
Tuberous Sclerosis ◽  
De Novo ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Tsc1 Gene

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.

An Update of Gorlin-Goltz Syndrome

2018 ◽  
Vol 7 (3) ◽  
pp. 38-41 ◽  
Author(s):  
Aliya Hasan ◽  
Dapo Akintola ◽  
Aliya Hasan ◽  
Dapo Akintola
Keyword(s):  
Clinical Signs ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Oral Manifestations ◽  
Early Referral ◽  
Goltz Syndrome ◽  
Dental Practitioners ◽  
Wide Range ◽  
Risk Of Malignancy ◽  
Clinical Signs And Symptoms

Gorlin-Goltz syndrome encompasses a variety of clinical signs and symptoms including important oral manifestations which general dental practitioners should be aware of. In light of the risk of malignancy it is important to be aware of this syndrome and recognise the need for early referral for multidisciplinary management. This paper aims to discuss Gorlin-Goltz syndrome, the pathophysiology of the condition and address the wide range of clinical manifestations. The author will pay particular attention to the oral manifestations of the condition and the management of such anomalies.

scholarly journals Autoimmune thyroiditis: clinical presentation in a Nepalese population

2014 ◽  
Vol 3 (1) ◽  
pp. 44-47
Author(s):  
K Paudel ◽  
B Paudel
Keyword(s):  
Clinical Presentation ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Primary Hypothyroidism ◽  
Cold Intolerance ◽  
Wide Range ◽  
Tingling Sensation ◽  
Pedal Edema ◽  
Antibody Levels ◽  
Hypothyroid Patients

Background: Hypothyroidism has a wide range of clinical presentations. This study was conducted to describe the clinical manifestations of chronic Hashimoto`s thyroiditis (HT) in a Nepalese population. We also tried to identify symptoms or signs characteristic for HT. Methods: During the study period, all newly diagnosed patients with hypothyroidism were interviewed about symptoms, and clinical signs were assessed. The data of hypothyroid patients were divided in two groups: TPO antibody positive and TPO antibody negative. The symptoms and signs of the two groups were analyzed and compared. Results: Among the 88 hypothyroid patients, 33 (37.5%) had positive TPO antibody levels. Female patients were more likely to be TPO antibody positive (41.3% among female and 15.4% among male). The most frequent symptoms were lethargy, cold intolerance, constipation, tingling sensation and weight gain, and the most frequent signs were facial puffiness and non-pitting pedal edema, in both groups. Statistical analysis revealed, that cold intolerance, decreased appetite and insomnia were significantly more prevalent symptoms in the TPO antibody positive group (p<0.05). Conclusion: Hashimoto`s thyroiditis is a common cause of primary hypothyroidism. It is not possible to differentiate it from the clinical presentation. Nepal Journal of Medical Sciences | Volume 03 | Number 01 | January-June 2014 | Page 68-71 DOI: http://dx.doi.org/10.3126/njms.v3i1.10362

scholarly journals Role of MxB in Alpha Interferon-Mediated Inhibition of HIV-1 Infection

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Bin Xu ◽  
Qinghua Pan ◽  
Chen Liang
Keyword(s):  
G Protein ◽  
Transmembrane Protein ◽  
Alpha Interferon ◽  
Wild Type Virus ◽  
Target Cells ◽  
Type I ◽  
Wide Range ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACTType I interferon inhibits viruses through inducing the expression of antiviral proteins, including the myxovirus resistance (Mx) proteins. Compared to the human MxA protein, which inhibits a wide range of viruses, the MxB protein has been reported to specifically inhibit primate lentiviruses, including HIV-1, and herpesviruses. Further, the role of endogenous MxB in alpha interferon-mediated inhibition of HIV-1 infection was questioned by a recent study showing that MxB knockout did not increase the level of infection by HIV-1 which carried the G protein of vesicular stomatitis virus (VSV), allowing infection of CD4-negative HT1080 cells. In order to further examine the anti-HIV-1 activity of endogenous MxB, we have used CRISPR/Cas9 to deplete MxB in different cell lines and observed a substantial restoration of HIV-1 infection in the presence of alpha interferon treatment. However, this rescue effect of MxB knockout became much less pronounced when infection was performed with HIV-1 carrying the VSV G protein. Interestingly, a CRISPR/Cas9 knockout screen of alpha interferon-stimulated genes in U87-MG cells revealed that the genes for interferon-induced transmembrane protein 2 (IFITM2) and IFITM3 inhibited VSV G-pseudotyped HIV-1 much more strongly than the rest of the genes tested, including the gene for MxB. Therefore, our results demonstrate the importance of MxB in alpha interferon-mediated inhibition of HIV-1 infection, which, however, can be underestimated if infection is performed with VSV G protein-pseudotyped HIV-1, due to the high sensitivity of VSV G-mediated infection to inhibition by IFITM proteins.IMPORTANCEThe results of this study reconcile the controversial reports regarding the anti-HIV-1 function of alpha interferon-induced MxB protein. In addition to the different cell types that may have contributed to the different observations, our data also suggest that VSV G protein-pseudotyped HIV-1 is much less inhibited by alpha interferon-induced MxB than HIV-1 itself is. Our results clearly demonstrate an important contribution of MxB to alpha interferon-mediated inhibition of HIV-1 in CD4+T cells, which calls for using HIV-1 target cells and wild-type virus to test the relevance of the anti-HIV-1 activity of endogenous MxB and other restriction factors.

scholarly journals New-onset IgG autoantibodies in hospitalized patients with COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah Esther Chang ◽  
Allan Feng ◽  
Wenzhao Meng ◽  
Sokratis A. Apostolidis ◽  
Elisabeth Mack ◽  
...  
Keyword(s):  
De Novo ◽  
Significant Proportion ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Structural Proteins ◽  
Rare Disorders ◽  
Autoantibody Production ◽  
Wide Range ◽  
Pathogenic Viruses ◽  
New Onset

AbstractCOVID-19 is associated with a wide range of clinical manifestations, including autoimmune features and autoantibody production. Here we develop three protein arrays to measure IgG autoantibodies associated with connective tissue diseases, anti-cytokine antibodies, and anti-viral antibody responses in serum from 147 hospitalized COVID-19 patients. Autoantibodies are identified in approximately 50% of patients but in less than 15% of healthy controls. When present, autoantibodies largely target autoantigens associated with rare disorders such as myositis, systemic sclerosis and overlap syndromes. A subset of autoantibodies targeting traditional autoantigens or cytokines develop de novo following SARS-CoV-2 infection. Autoantibodies track with longitudinal development of IgG antibodies recognizing SARS-CoV-2 structural proteins and a subset of non-structural proteins, but not proteins from influenza, seasonal coronaviruses or other pathogenic viruses. We conclude that SARS-CoV-2 causes development of new-onset IgG autoantibodies in a significant proportion of hospitalized COVID-19 patients and are positively correlated with immune responses to SARS-CoV-2 proteins.

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