scholarly journals Adolescent autism and autoimmune diagnoses linked to infant gut bacteria whose prevalence is associated with at-risk genetics and/or diet

2021 ◽  
Author(s):  
Patricia L. Turpin ◽  
Angelica P. Ahrens ◽  
Jordan T. Russell ◽  
Erik Kindgren ◽  
Meghan A. Berryman ◽  
...  
Keyword(s):  
At Risk ◽  
Autoimmune Diseases ◽  
Gut Microbiome ◽  
Disease Onset ◽  
Class Ii ◽  
Dietary Factors ◽  
Bacterial Strains ◽  
Crohns Disease ◽  
Gut Colonization ◽  
One Year

The earliest predictors of future autoimmune diseases are a series of autoantibodies that are rarely evaluated and very within and between diseases. In addition, autoantibodies often appear just prior to disease onset. All of these factors make it difficult to apply interventions that might prevent disease. Earlier predictors of disease are needed. Here, a general population cohort was used to assess whether gut bacterial biomarkers could be identified prior to disease. Gut microbiome analysis on 1,741 one-year old Swedish children was performed on samples collected in the late 1990s. These children were then followed for 18 years for the incidence of five autoimmune diseases and autism. Specific bacterial strains in the gut microbiome of one-year-old children have been identified as exclusive to the 96 subjects (cases) who acquired type 1 diabetes, celiac disease, hypothyroidism, Crohns disease, juvenile idiopathic arthritis, or autism over their next 18 years. None of these strains were found in the 1,645 children (controls) who did not acquire any of these diseases. Ten other strains were exclusive to those who remained disease-free. In most cases, the presence or absence of these bacteria were strongly associated with: 1) high-risk class II human leukocyte antigen (HLA) alleles; 2) dietary factors; or 3) a combination of HLA genetics and diet. These results have three significant implications: 1) certain class II HLA haplotypes may serve as bacterial gatekeepers early in life, altering microbiome composition thereby creating the potential for dysbiosis and inflammation; 2) the gut microbiome dysbiosis and inflammation during infancy, largely derived from host HLA genetics and diet, may be a common precedent to all five autoimmune diseases and autism; and 3) HLA gatekeeping may prevent gut colonization of beneficial bacteria in those genetically at-risk individuals who could most benefit from probiotic therapy.

Stria Vascularis Ultrastructural Pathology in the C3H/lpr Autoimmune Strain Mouse: A Potential Mechanism for Immune-Related Hearing Loss

1992 ◽  
Vol 106 (3) ◽  
pp. 288-295 ◽  
Author(s):  
Ilsa Schwartz ◽  
Sean O. McMenomey ◽  
Nancy J. Russell ◽  
Jane I. Morton ◽  
Dennis R. Trune
Keyword(s):  
Hearing Loss ◽  
Autoimmune Disease ◽  
Basement Membrane ◽  
Autoimmune Diseases ◽  
Stria Vascularis ◽  
Disease Onset ◽  
Systemic Autoimmune Disease ◽  
Potential Mechanism ◽  
Systemic Autoimmune Diseases ◽  
Strain Mouse

The stria vascularis in the C3H/ lpr autoimmune strain mouse was ultrastructurally examined in order to better understand the potential mechanisms by which systemic autoimmune disease affects the ear. The inner ears from C3H/ lpr mice before disease onset and C3H/HeJ controls showed no apparent pathology. However, the stria vascularis from older C3H/ lpr mice after systemic autoimmune disease onset showed considerable intercellular edema around the stria capillaries and thickening of the capillary basement membrane, compared to controls. These observations suggest that perivascular abnormalities, which are the hallmark of systemic autoimmune diseases, may underlie the stria dysfunction and hearing loss seen in autoimmune diseases in humans.

scholarly journals Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Cruz-Tapias ◽  
Oscar M. Pérez-Fernández ◽  
Adriana Rojas-Villarraga ◽  
Alberto Rodríguez-Rodríguez ◽  
María-Teresa Arango ◽  
...  
Keyword(s):  
Risk Factor ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Genetic Characteristics ◽  
Latin Americans ◽  
Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

scholarly journals HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.

1996 ◽  
Vol 183 (6) ◽  
pp. 2635-2644 ◽  
Author(s):  
K Ito ◽  
H J Bian ◽  
M Molina ◽  
J Han ◽  
J Magram ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Diseases ◽  
Mhc Class Ii ◽  
Experimental Allergic Encephalomyelitis ◽  
Class Ii ◽  
Antigen Binding ◽  
Allergic Encephalomyelitis ◽  
Alpha Beta ◽  
Deficient Mice ◽  
Experimental Allergic

To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87-106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.

Parent-Mediated Intervention for One-Year-Olds Screened as At-Risk for Autism Spectrum Disorder: A Randomized Controlled Trial

2017 ◽  
Vol 47 (11) ◽  
pp. 3520-3540 ◽  
Author(s):  
Linda R. Watson ◽  
Elizabeth R. Crais ◽  
Grace T. Baranek ◽  
Lauren Turner-Brown ◽  
John Sideris ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
At Risk ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Randomized Controlled ◽  
One Year

scholarly journals Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease

2019 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna-Katharina von Thaler ◽  
Claudia Schulte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Physical Inactivity ◽  
Disease Onset ◽  
Rem Sleep Behavior Disorder ◽  
Sleep Behavior ◽  
Microbiome Composition ◽  
Β Diversity ◽  
The Impact

AbstractObjectivesAlterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

scholarly journals Explaining the association between urbanicity and psychotic-like experiences in adolescence: The indirect effect of urban exposures

2021 ◽  
Author(s):  
Abhishek Saxena ◽  
David Dodell-Feder
Keyword(s):  
At Risk ◽  
Indirect Effect ◽  
Public Health Intervention ◽  
The United States ◽  
Urban Environments ◽  
Income Disparity ◽  
Lead Paint ◽  
Increased Risk ◽  
Worldwide Phenomenon ◽  
One Year

Urban living is a growing worldwide phenomenon with more than two-thirds of people expected to live in cities by 2050. Although there are many benefits to living in an urban environment, urbanicity has also been associated with deleterious health outcomes, including increased risk for psychotic outcomes particularly when the urban exposure occurs in adolescence. However, the mechanisms underlying this association is unclear. Here, we utilize one-year follow-up data from a large (N=7,979), nationwide study of adolescence in the United States to clarify why urbanicity might impact psychotic-like experiences (PLE) by looking at the indirect effect of eight candidate urbanicity-related physical (e.g., pollution) and social (e.g., poverty) exposures. Consistent with other work, we find that of the evaluated exposures related to urbanicity, several were also related to increased number of PLE and associated distress: PM2.5, proximity to roads, census-level homes at-risk for exposure to lead paint, census-level poverty, and census-level income-disparity. Mediation analysis revealed that a substantial proportion the urbanicity-PLE association could be explained by PM2.5 (23% of the urbanicity-PLE number association), families in poverty (57-67% of the urbanicity-PLE number and distress association), and income disparity (55-66% of the urbanicity-PLE number and distress association). Together, these findings suggest that specific urban-related exposures might help to explain why those in urban environments are disproportionately at-risk for psychosis and point towards areas for public health intervention.

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