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2.
Am J Transplant ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917505

RESUMO

US deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd-SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd-SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd-SOT, and (3) receiving dd-SOT. Lifetime Pr (per 100 000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd-SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd-SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd-SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd-SOT, which may assist with reframing motivations toward deceased donor organ donation.

3.
MMWR Morb Mortal Wkly Rep ; 69(2): 35-39, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31945033

RESUMO

Transgender women* in the United States are disproportionately affected by human immunodeficiency virus (HIV) infection because of multiple factors, including stigma related to gender identity, unstable housing, limited employment options, and high-risk behaviors, such as sex work, unprotected receptive anal intercourse, and injection drug use, that tend to increase their vulnerability to becoming infected with HIV (1,2). In a recent meta-analysis of 88 U.S. studies conducted during 2006-2017, the mean estimated laboratory-confirmed prevalence of HIV infection among transgender women was 14.2%, and the mean self-reported prevalence estimate was 21.0% (3). The Ending the HIV Epidemic initiative calls for accelerating the implementation of evidence-based strategies in the right geographic areas targeted to the right persons to end the HIV epidemic in the United States (4). HIV partner services are effective strategies offered by public health workers to persons with a diagnosis of HIV infection (index persons) and their sex or needle-sharing partners (partners), who are notified of potential HIV exposure and offered HIV testing and related services. CDC analyzed HIV partner services data submitted by 61 health departments† during 2013-2017. Among 208,304 index persons, 1,727 (0.8%) were transgender women. Overall, 71.5% of index transgender women were interviewed for partner services, which was lower than that for all index persons combined (81.1%). Among 1,089 transgender women named as partners by index persons, 71.2% were notified of potential HIV exposure, which was lower than that for all partners combined (77.1%). Fewer than half (46.5%) of notified transgender women partners were tested for HIV, and approximately one in five (18.6%) of those who were tested received a new diagnosis of HIV infection, slightly higher than for all partners combined (17.6%). Additional efforts are needed to effectively implement partner services among transgender women and identify those whose infection with HIV is undiagnosed, provide timely prevention and care services, reduce HIV transmission, and contribute to ending the HIV epidemic.


Assuntos
Assistência à Saúde , Infecções por HIV/terapia , Parceiros Sexuais , Pessoas Transgênero , Adolescente , Adulto , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Estados Unidos/epidemiologia , Adulto Jovem
4.
Sci Immunol ; 4(42)2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811053

RESUMO

Autoantibodies that recognize the glycine receptor mediate pathology by directly interrupting glycinergic neurotransmission that manifests as a disorder characterized by muscle stiffness and spasms.

5.
Curr Opin Biotechnol ; 62: 212-219, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31881445

RESUMO

The envisaged circular economy requires absolute carbon efficiency and in the long run abstinence from fossil feedstocks, and integration of industrial production with end-of-life waste management. Non-conventional feedstocks arising from industrial production and societal consumption such as CO2 and plastic waste may soon enable manufacture of multiple products from simple bulk chemicals to pharmaceuticals using biotechnology. The change to these feedstocks could be faster than expected by many, especially if the true cost, including the carbon footprint of products, is considered. The efficiency of biotechnological processes can be improved through metabolic engineering, which can help fulfill the promises of the Paris agreement.

6.
Immunol Rev ; 292(1): 90-101, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31721234

RESUMO

A role for B cells in autoimmune diseases is now clearly established both in mouse models and humans by successful treatment of multiple sclerosis and rheumatoid arthritis with anti-CD20 monoclonal antibodies that eliminate B cells. However, the underlying mechanisms by which B cells promote the development of autoimmune diseases remain poorly understood. Here, we review evidence that patients with autoimmune disease suffer from defects in early B-cell tolerance checkpoints and therefore fail to counterselect developing autoreactive B cells. These B-cell tolerance defects are primary to autoimmune diseases and may result from altered B-cell receptor signaling and dysregulated T-cell/regulatory T-cell compartment. As a consequence, large numbers of autoreactive naive B cells accumulate in the blood of patients with autoimmune diseases and may promote autoimmunity through the presentation of self-antigen to T cells. In addition, new evidence suggests that this reservoir of autoreactive naive B cells contains clones that may develop into CD27- CD21-/lo B cells associated with increased disease severity and plasma cells secreting potentially pathogenic autoantibodies after the acquisition of somatic hypermutations that improve affinity for self-antigens.

7.
PLoS One ; 14(8): e0218558, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412030

RESUMO

Effective conservation and restoration of estuarine wetlands require accurate maps of their historical and current extent, as well as estimated losses of these valued habitats. Existing coast-wide tidal wetland mapping does not explicitly map historical tidal wetlands that are now disconnected from the tides, which represent restoration opportunities; nor does it use water level models or high-resolution elevation data (e.g. lidar) to accurately identify current tidal wetlands. To better inform estuarine conservation and restoration, we generated new maps of current and historical tidal wetlands for the entire contiguous U.S. West Coast (Washington, Oregon, and California). The new maps are based on an Elevation-Based Estuary Extent Model (EBEEM) that combines lidar digital elevation models (DEMs) and water level models to establish the maximum historical extent of tidal wetlands, representing a major step forward in mapping accuracy for restoration planning and analysis of wetland loss. Building from this new base, we also developed an indirect method for mapping tidal wetland losses, and created maps of these losses for 55 estuaries on the West Coast (representing about 97% of historical West Coast vegetated tidal wetland area). Based on these new maps, we estimated that total historical estuary area for the West Coast is approximately 735,000 hectares (including vegetated and nonvegetated areas), and that about 85% of vegetated tidal wetlands have been lost from West Coast estuaries. Losses were highest for major river deltas. The new maps will help interested groups improve action plans for estuarine wetland habitat restoration and conservation, and will also provide a better baseline for understanding and predicting future changes with projected sea level rise.

8.
J Immunol ; 203(6): 1650-1664, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31391234

RESUMO

IgD-CD27- double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgD-CD27+ class-switched memory (CSM) and IgD+CD27- naive B cells of HC (n = 48) and MS patients (n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients (n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95+ and IgA+ cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.

9.
Sci Immunol ; 4(37)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278122

RESUMO

Pathogenic autoantibodies in neuromyelitis optica require antigen array assembly and a specific epitope to initiate robust complement activation.

10.
Colloids Surf B Biointerfaces ; 182: 110333, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288131

RESUMO

A sodium alkyl disulfate mixture (SADM) synthesised from microbially produced 3-hydroxy fatty acids methyl esters (HFAMEs), showed 13-fold surface tension decrease when compared with the reference surfactant sodium dodecyl sulfate (SDS). Polyhydroxyalkanoates, accumulated by bacteria intracellularly when supplied with a mixture of fatty acids derived from hydrolysed rapeseed oil, were isolated, depolymerised and methylated to produce HFAMEs in very high yield (90%). A sequential chemical reduction and sulfation of the HFAMEs produced the sodium alkyl disulfates in high yields (>65%). SADM performs also 1.3-times better than dodecyl (1,3) disulfate, in surface tension tests. SADM shows also the formation of a specific critical micelle concentration (CMC) at a concentration 21-fold lower than SDS. The wettability of the SADM mixture is similar to SDS but the foaming volume of SADM is 1.5-fold higher. The foam is also more stable with its volume decreasing 3 times slower over time compared to SDS at their respective CMC values. Established sulfation technologies in chemical manufacturing could use the 3-hydroxy fatty acids methyl esters moiety (3-HFAME) given its origin from rapeseed oil and the extra OH residue on 3-position in the molecule, which affords the opportunity to produce disulfate surfactants with a proven superior performance to monosulphated surfactants. Thus, not only addressing environmental issues by avoiding threats of deforestation and monocultivation associated with palm oil use but also achieve a higher performance with lower use of surfactants.

11.
Appl Microbiol Biotechnol ; 103(15): 5957-5974, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177312

RESUMO

Hydroxytyrosol (HT) is a polyphenol of interest to the food, feed, supplements and pharmaceutical sectors. It is one of the strongest known natural antioxidants and has been shown to confer other benefits such as anti-inflammatory and anti-carcinogenic properties, and it has the potential to act as a cardio- and neuroprotectant. It is known to be one of the compounds responsible for the health benefits of the Mediterranean diet. In nature, HT is found in the olive plant (Olea europaea) as part of the secoiridoid compound oleuropein, in its leaves, fruit, oil and oil production waste products. HT can be extracted from these olive sources, but it can also be produced by chemical synthesis or through the use of microorganisms. This review looks at the production of HT using plant extraction, chemical synthesis and biotechnological approaches.


Assuntos
Antioxidantes/isolamento & purificação , Biotecnologia/métodos , Álcool Feniletílico/análogos & derivados , Tecnologia Farmacêutica/métodos , Antioxidantes/síntese química , Antioxidantes/metabolismo , Olea/química , Álcool Feniletílico/síntese química , Álcool Feniletílico/isolamento & purificação , Álcool Feniletílico/metabolismo
12.
JCI Insight ; 4(12)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31217355

RESUMO

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by muscle weakness and caused by pathogenic autoantibodies that bind to membrane proteins at the neuromuscular junction. Most patients have autoantibodies against the acetylcholine receptor (AChR), but a subset of patients have autoantibodies against muscle-specific tyrosine kinase (MuSK) instead. MuSK is an essential component of the pathway responsible for synaptic differentiation, which is activated by nerve-released agrin. Through binding MuSK, serum-derived autoantibodies inhibit agrin-induced MuSK autophosphorylation, impair clustering of AChRs, and block neuromuscular transmission. We sought to establish individual MuSK autoantibody clones so that the autoimmune mechanisms could be better understood. We isolated MuSK autoantibody-expressing B cells from 6 MuSK MG patients using a fluorescently tagged MuSK antigen multimer, then generated a panel of human monoclonal autoantibodies (mAbs) from these cells. Here we focused on 3 highly specific mAbs that bound quantitatively to MuSK in solution, to MuSK-expressing HEK cells, and at mouse neuromuscular junctions, where they colocalized with AChRs. These 3 IgG isotype mAbs (2 IgG4 and 1 IgG3 subclass) recognized the Ig-like domain 2 of MuSK. The mAbs inhibited AChR clustering, but intriguingly, they enhanced rather than inhibited MuSK phosphorylation, which suggests an alternative mechanism for inhibiting AChR clustering.

13.
Brain ; 142(6): 1598-1615, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31056665

RESUMO

Neuromyelitis optica spectrum disorders (NMOSD) constitute rare autoimmune disorders of the CNS that are primarily characterized by severe inflammation of the spinal cord and optic nerve. Approximately 75% of NMOSD patients harbour circulating pathogenic autoantibodies targeting the aquaporin-4 water channel (AQP4). The source of these autoantibodies remains unclear, but parallels between NMOSD and other autoantibody-mediated diseases posit compromised B cell tolerance checkpoints as common underlying and contributing factors. Using a well established assay, we assessed tolerance fidelity by creating recombinant antibodies from B cell populations directly downstream of each checkpoint and testing them for polyreactivity and autoreactivity. We examined a total of 863 recombinant antibodies. Those derived from three anti-AQP4-IgG seropositive NMOSD patients (n = 130) were compared to 733 antibodies from 15 healthy donors. We found significantly higher frequencies of poly- and autoreactive new emigrant/transitional and mature naïve B cells in NMOSD patients compared to healthy donors (P-values < 0.003), thereby identifying defects in both central and peripheral B cell tolerance checkpoints in these patients. We next explored whether pathogenic NMOSD anti-AQP4 autoantibodies can originate from the pool of poly- and autoreactive clones that populate the naïve B cell compartment of NMOSD patients. Six human anti-AQP4 autoantibodies that acquired somatic mutations were reverted back to their unmutated germline precursors, which were tested for both binding to AQP4 and poly- or autoreactivity. While the affinity of mature autoantibodies against AQP4 ranged from modest to strong (Kd 15.2-559 nM), none of the germline revertants displayed any detectable binding to AQP4, revealing that somatic hypermutation is required for the generation of anti-AQP4 autoantibodies. However, two (33.3%) germline autoantibody revertants were polyreactive and four (66.7%) were autoreactive, suggesting that pathogenic anti-AQP4 autoantibodies can originate from the pool of autoreactive naïve B cells, which develops as a consequence of impaired early B cell tolerance checkpoints in NMOSD patients.

14.
Neurol Neuroimmunol Neuroinflamm ; 6(3): e552, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31119187

RESUMO

Objective: We sought to validate methods for detection and confirmation of GABAA receptor (R)-IgG and clinically characterize seropositive cases. Methods: Archived serum and CSF specimens (185 total) suspected to harbor GABAAR-IgG were evaluated by indirect immunofluorescence assay (IFA). Twenty-six specimens from 19 patients appeared suspicious for GABAAR-IgG positivity by IFA, based on prior reports and comparison with commercial GABAAR antibody staining. Aliquots of those specimens were tested at the University of Oxford, United Kingdom, and Euroimmun, Lubeck, Germany, for GABAAR-IgG by cell-based assays (CBAs) using HEK293-indicator cells transfected with plasmids encoding different GABAAR subunits. Results: Eight specimens (of 26 tested; 4 serums, 4 CSFs) from 5 patients were confirmed by CBA to be GABAAR-IgG positive. Patient IgGs were always reactive with α1ß3 GABAAR subunits. One more patient was identified clinically after this validation study. Median age for the 6 patients at serologic diagnosis was 44 years (range, 1-71 years), and 4 of them were male. Among the 4 for whom clinical information was available (2 treated by the authors), all had encephalitis and antiepileptic drug refractory seizures. Three out of 4 patients treated with a combination of immunotherapies had good outcomes. The fourth, recognized to have an autoimmune cause late in the clinical course, had severe permanent neurologic sequelae and brain atrophy. Conclusions: Though not as common as NMDA-R encephalitis, GABAAR encephalitis generally has a characteristic clinical-radiologic presentation and is treatable, making accurate laboratory diagnosis critical.

15.
World J Microbiol Biotechnol ; 35(4): 67, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30963257

RESUMO

Unnatural amino acids (UAAs) are valuable building blocks in the manufacture of a wide range of pharmaceuticals. UAAs exhibit biological activity as free acids and they can be incorporated into linear or cyclic peptides with biological activity. However, the scope of biotechnological application of UAAs goes beyond this, as they can be used to investigate the structure and dynamics of proteins, to study protein interactions, or to modulate the activity of proteins in living cells. The means to expand nature's repertoire of amino acids include chemical and biological routes. An UAA can be made through chemical modifications of natural amino acids, or related compounds. These modifications typically rely on utilisation of ligands and palladium catalysts. Employing biocatalysts in the synthesis of UAAs can also afford novel molecules with different physical and chemical properties. A number of transaminases for example have been identified and employed in the production of UAAs. This review will compare the chemical and biological routes for the synthesis of UAAs and provide an overview of their applications.


Assuntos
Aminoácidos/biossíntese , Aminoácidos/síntese química , Biotecnologia/métodos , Aminoácidos/química , Biocatálise , Enzimas/metabolismo , Engenharia Metabólica , Engenharia de Proteínas/métodos
16.
EBioMedicine ; 42: 76-85, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952617

RESUMO

BACKGROUND: Autoimmune disease prevention requires tools to assess an individual's risk of developing a specific disease. One tool is disease-associated autoantibodies, which accumulate in an asymptomatic preclinical period. However, patients sometimes exhibit autoantibodies associated with a different disease classification. When and how these alternative autoantibodies first appear remain unknown. This cross-sectional study characterizes alternative autoimmunity, and associated genetic and environmental factors, in unaffected first-degree relatives (FDRs) of patients, who exhibit increased future risk for the same disease. METHODS: Samples (n = 1321) from disease-specific autoantibody-positive (aAb+) systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes (T1D) patients; and unaffected aAb+ and autoantibody-negative (aAb-) SLE and RA FDRs were tested for SLE, RA, and T1D aAbs, as well as anti-tissue transglutaminase, anti-cardiolipin and anti-thyroperoxidase. FDR SLE and RA genetic risk scores (GRS) were calculated. FINDINGS: Alternative autoimmunity occurred in SLE patients (56%) and FDRs (57·4%), RA patients (32·6%) and FDRs (34·8%), and T1D patients (43%). Expanded autoimmunity, defined as autoantibodies spanning at least two other diseases, occurred in 18·5% of SLE patients, 16·4% of SLE FDRs, 7·8% of RA patients, 5·3% of RA FDRs, and 10·8% of T1D patients. SLE FDRs were more likely to have alternative (odds ratio [OR] 2·44) and expanded (OR 3·27) autoimmunity than RA FDRs. Alternative and expanded autoimmunity were associated with several environmental exposures. Alternative autoimmunity was associated with a higher RA GRS in RA FDRs (OR 1·41), and a higher SLE GRS in aAb+ RA FDRs (OR 1·87), but not in SLE FDRs. INTERPRETATION: Autoimmunity commonly crosses disease-specific boundaries in systemic (RA, SLE) and organ-specific (T1D) autoimmune diseases. Alternative autoimmunity is more common in SLE FDRs than RA FDRs, and is influenced by genetic and environmental factors. These findings have substantial implications for preclinical disease pathogenesis and autoimmune disease prevention studies. FUND: NIH U01AI101981, R01AR051394, U19AI082714, P30AR053483, P30GM103510, U54GM104938, U01AI101934, R01AI024717, U01AI130830, I01BX001834, & U01HG008666.


Assuntos
Artrite Reumatoide/etiologia , Autoimunidade/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/etiologia , Núcleo Familiar , Adulto , Idoso , Alelos , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Meio Ambiente , Feminino , Frequência do Gene , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos/imunologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
17.
Front Immunol ; 10: 129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814994

RESUMO

The adaptive immune receptor repertoire (AIRR) contains information on an individuals' immune past, present and potential in the form of the evolving sequences that encode the B cell receptor (BCR) repertoire. AIRR sequencing (AIRR-seq) studies rely on databases of known BCR germline variable (V), diversity (D), and joining (J) genes to detect somatic mutations in AIRR-seq data via comparison to the best-aligning database alleles. However, it has been shown that these databases are far from complete, leading to systematic misidentification of mutated positions in subsets of sample sequences. We previously presented TIgGER, a computational method to identify subject-specific V gene genotypes, including the presence of novel V gene alleles, directly from AIRR-seq data. However, the original algorithm was unable to detect alleles that differed by more than 5 single nucleotide polymorphisms (SNPs) from a database allele. Here we present and apply an improved version of the TIgGER algorithm which can detect alleles that differ by any number of SNPs from the nearest database allele, and can construct subject-specific genotypes with minimal prior information. TIgGER predictions are validated both computationally (using a leave-one-out strategy) and experimentally (using genomic sequencing), resulting in the addition of three new immunoglobulin heavy chain V (IGHV) gene alleles to the IMGT repertoire. Finally, we develop a Bayesian strategy to provide a confidence estimate associated with genotype calls. All together, these methods allow for much higher accuracy in germline allele assignment, an essential step in AIRR-seq studies.


Assuntos
Imunoglobulinas/genética , Algoritmos , Alelos , Teorema de Bayes , Genótipo , Humanos , Miastenia Gravis/imunologia , Análise de Sequência de DNA
18.
Bioorg Chem ; 87: 209-217, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901676

RESUMO

Rhamnolipids are biodegradable low toxic biosurfactants which exert antimicrobial and anti-biofilm properties. They have attracted much attention recently due to potential applications in areas of bioremediation, therapeutics, cosmetics and agriculture, however, the full potential of these versatile molecules is yet to be explored. Based on the facts that many naturally occurring lipopeptides are potent antimicrobials, our study aimed to explore the potential of replacing rhamnose in rhamnolipids with amino acids thus creating lipopeptides that would mimic or enhance properties of the parent molecule. This would allow not only for more economical and greener production but also, due to the availability of structurally different amino acids, facile manipulation of physico-chemical and biological properties. Our synthetic efforts produced a library of 43 lipopeptides revealing biologically more potent molecules. The structural changes significantly increased, in particular, anti-biofilm properties against Candida albicans, although surface activity of the parent molecule was almost completely abolished. Our findings show that the most active compounds are leucine derivatives of 3-hydroxy acids containing benzylic ester functionality. The SAR study demonstrated a further increase in activity with aliphatic chain elongation. The most promising lipopeptides 15, 23 and 36 at 12.5 µg/mL concentration allowed only 14.3%, 5.1% and 11.2% of biofilm formation, respectively after 24 h. These compounds inhibit biofilm formation by preventing adhesion of C. albicans to abiotic and biotic surfaces.

19.
J Immunol ; 202(8): 2210-2219, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30824481

RESUMO

The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) (n = 194, HD n = 64), 2) type 1 diabetes (T1D) (n = 200, HD n = 200), 3) systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neurologic autoimmunity (relapsing-remitting multiple sclerosis [MS] n = 110, HD n = 110; primary progressive MS n = 9; secondary progressive MS n = 10; neuromyelitis optica spectrum disorders n = 15; and other neurologic disorders n = 26). Screening of 1287 unique serum samples against four neurologic surface Ags (myelin oligodendrocyte glycoprotein, aquaporin 4, acetylcholine receptor, and muscle-specific kinase) was performed with live cell-based immunofluorescence assays using flow cytometry. Positive samples identified in the screening were further validated using autoantibody titer quantification by serial dilutions or radioimmunoassay. Autoantibodies against neurologic surface Ags were not observed in RA and T1D patients, whereas SLE patients harbored such autoantibodies in rare cases (2/200, 1%). Within the CNS autoimmunity control cohort, autoantibodies against aquaporin 4 and high-titer Abs against myelin oligodendrocyte glycoprotein were, as expected, specific for neuromyelitis optica spectrum disorders. We conclude that neurologic autoantibodies do not cross disease barriers in RA and T1D. The finding of mildly increased neurologic autoantibodies in SLE may be consistent with a broader loss of B cell tolerance in this form of systemic autoimmunity.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Proteínas do Tecido Nervoso/imunologia , Doenças Autoimunes/patologia , Linfócitos B/patologia , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade
20.
MMWR Morb Mortal Wkly Rep ; 68(4): 81-86, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703079

RESUMO

Identifying persons with human immunodeficiency virus (HIV) infection who are unaware of their infection status, linking them to HIV care, and reducing racial/ethnic disparities are important national HIV prevention goals (1). Blacks/African Americans (blacks)* are disproportionately affected by HIV infection in the United States. Although blacks represent 13% of the U.S. population (2), in 2017, 44% of diagnoses of HIV infection were in blacks, and the rate of new diagnoses in blacks (41.1 per 100,000 persons) was approximately eight times that of non-Hispanic whites (5.1) (3). HIV partner services are offered by health officials to persons with diagnosed HIV infection (index patients) and their sex- or needle-sharing partners, who are notified of their potential HIV exposure and offered HIV testing and related services (4). CDC analyzed 2016 data from the National HIV Prevention Program Monitoring and Evaluation system submitted by 59 health departments.† Among 49,266 index patients identified as potential candidates for partner services, 21,191 (43%) were black. The percentage of black index patients interviewed for partner services (76%) was higher than that for all index patients combined (73%). Among the 11,088 black partners named by index patients, 78% were notified of their potential HIV exposure. Fewer than half (47%) of those notified were tested for HIV infection. Among those tested, one in six (17%) received a new HIV diagnosis. The prevalence of newly diagnosed HIV infection was particularly high among black partners who were gay, bisexual, and other men who have sex with men (MSM) (37%) and transgender persons (38%). Effective implementation of partner services is important to identify HIV infection, link patients to care or reengage them in care, and provide prevention services to reduce HIV transmission.


Assuntos
Afro-Americanos/estatística & dados numéricos , Assistência à Saúde/etnologia , Infecções por HIV/etnologia , Parceiros Sexuais , Adolescente , Adulto , Feminino , Infecções por HIV/terapia , Pesquisas sobre Serviços de Saúde , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
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