Autism, Leishmaniasis, Vitiligo, Psoriasis, Graves' disease, rheumatoid arthritis, celiac disease, ankylosing spondylitis, T1 diabetes, myasthenia gravis, Sjögren syndrome, mold toxicity, thyroiditis, etc.
Table of contents
- Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD) – Sept 2019
- Human Leukocyte Antigen – 1 hour podcast
- HLA-B and Autism in Thailand – 2017
- Immune Dysfunction in Autism Spectrum Disorder – 2011 (HLA occurs 54 times)
- HLA and Disease Associations – Book, 1985
- Wonder if there has been an increase some diseases due to poor HLA genes being passed on to children?
Front. Psychiatry 10:612. doi: 10.3389/fpsyt.2019.00612
Not all Autistics have HLA-Cw7 problems.
Only some Autistics have HLA-Cw7 positive features and not negative features
HLA-Cw7 might be a subtype of all Autisms
Terry Harville12 Bobbie Rhodes-Clark1, Sirish C. Bennuri35, Leanna Delhey4’5,
John Slattery6, Marie Tippett35, Rebecca Wynne7, Shannon Rose35, Stephen Kahler35 and Richard E. Frye8'9*
1 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States,2 Department of internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States, 3 Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States, 4 School of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States, 5 Arkansas Children’s Research institute, Little Rock, AR, United States, 6 BioRosa Technologies inc, San Francisco, CA, United States, 7 National Center for Toxicological Research, Jefferson, AR, United States,8 Barrow Neurological institute at Phoenix Children’s Hospital, Phoenix, AZ, United States,9 Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ, United States
Autism spectrum disorder (ASD) is a behaviorally defined disorder that is now thought to affect approximately 1 in 69 children in the United States. In most cases, the etiology is unknown, but several studies point to the interaction of genetic predisposition with environmental factors. The immune system is thought to have a causative role in ASD, and specific studies have implicated T lymphocytes, monocytes, natural killer (NK) cells, and certain cytokines. The human leukocyte antigen (HLA) system is involved in the underlying process for shaping an individual’s immune system, and specific HLA alleles are associated with specific diseases as risk factors. In this study, we determine whether a specific HLA allele was associated with ASD in a large cohort of patients with ASD. Identifying such an association could help in the identification of immune system components which may have a causative role in specific cohorts of patients with ASD who share similar specific clinical features. Specimens from 143 patients with ASD were analyzed with respect to race and ethnicity. Overall, HLA-Cw7 was present in a much greater frequency than expected in individuals with ASD as compared to the general population. Further, the cohort of patients who express HLA-Cw7 shares specific immune system/inflammatory clinical features including being more likely to have allergies, food intolerances, and chronic sinusitis as compared to those with ASD who did not express HLA-Cw7. HLA-Cw7 has a role in stimulating NK cells. Thus, this finding may indicate that chronic over-activation of NK cells may have a role in the manifestation of ASD in a cohort of patients with increased immune system/inflammatory features.
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- Christensen DL, Braun KVN, Baio J, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveill Summ (2018) 65(13):1-23. doi: 10.15585/mmwr.ss6513a1
- Wiggins L, Christensen D, Van Naarden Braun K, Martin L, Baio J. Comparison of autism spectrum disorder surveillance status based on two different diagnostic schemes: findings from the metropolitan atlanta developmental disabilities surveillance program, 2012. PLoS One (2018) 13(11):e0208079. doi: 10.1371/journal.pone.0208079
- Rossignol DA, Frye RE. A review of research trends in physiological abnormalities in autism spectrum disorders: immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures. Mol Psychiatry (2012) 17(4):389-401. doi: 10.1038/mp.2011.165
- Rossignol DA, Genuis SJ, Frye RE. Environmental toxicants and autism spectrum disorders: a systematic review. Transi Psychiatry (2014) 4:e360. doi: 10.1038/tp.2014.4
- McDougle CJ, Landino SM, Vahabzadeh A, O'Rourke J, Zürcher NR, Finger BC, et al. Toward an immune-mediated subtype of autism spectrum disorder. Brain Res (2015) 1617:72-92. doi: 10.1016/j.brainres.2014.09.048
- Stubbs EG, Magenis RE. HLA and autism. J Autism Dev Disord (1980) 10(1):15-9.
- Torres AR, Maciulis A, Stubbs EG, Cutler A, Odell D. The transmission disequilibrium test suggests that HLA-DR4 and DR13 are linked to autism spectrum disorder. Hum Immunol (2002) 63(4):311-6.
- Lee LC, Zachary AA, Leffell MS, Newschaffer CJ, Matteson KJ, Tyler JD, et al. HLA-DR4 in families with autism. Pediatr Neurol (2006) 35(5):303-7. doi: 10.1016/j.pediatrneurol.2006.06.006
- Torres AR, Sweeten TL, Cutler A, Bedke BJ, Fillmore M, Stubbs EG, et al. The association and linkage of the HLA-A2 class I allele with autism. Hum Immunol (2006) 67(4-5):346-51. doi: 10.1016/j.humimm.2006.01.001
- Chien YL, Wu YY, Chen CH, Gau SS, Huang YS, Chien WH, et al. Association of HLA-DRB1 alleles and neuropsychological function in autism. Psychiatr Genet (2012) 22(1):46-9. doi: 10.1097/YPG.0b013e32834915ae
- Torres AR, Westover JB, Gibbons C, Johnson RC, Ward DC. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism. Brain Behav Immun (2012) 26(7):1122-7. doi: 10.1016/j.bbi.2012.07.014
- Al-Hakbany M, Awadallah S, Al-Ayadhi L. The relationship of HLA class I and II alleles and haplotypes with autism: a case control study. Autism Res Treat (2014) 2014:242048. doi: 10.1155/2014/242048
- Torres AR, Sweeten TL, Johnson RC, Odell D, Westover JB, Bray-Ward P, et al. Common genetic variants found in HLA and KIR immune genes in autism spectrum disorder. Front Neurosci (2016) 10:463. doi: 10.3389/ fnins.2016.00463
- Edmiston E, Ashwood P, Van de Water J. Autoimmunity, autoantibodies, and autism spectrum disorder. Biol Psychiatry (2017) 81(5):383-90. doi: 10.1016/j.biopsych.2016.08.031
- Connery K, Tippett M, Delhey LM, Rose S, Slattery JC, Kahler SG, et al. Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism. Transl Psychiatry (2018) 8(1):148. doi: 10.1038/s41398-018-0214-7
- Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol (2005) 57(1):67-81. doi: 10.1002/ana.20315
- Warren RP, Foster A, Margaretten NC. Reduced natural killer cell activity in autism. J Am Acad Child Adolesc Psychiatry (1987) 26(3):333-5. doi: 10.1097/00004583-198705000-00008
- Vojdani A, Mumper E, Granpeesheh D, Mielke L, Traver D, Bock K, et al. Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15. J Neuroimmunol (2008) 205(1-2):148-54. doi: 10.1016/ j.jneuroim.2008.09.005
- Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen RL, Pessah IN, et al. Altered gene expression and function of peripheral blood natural killer cells in children with autism. Brain Behav Immun (2009) 23(1):124-33. doi: 10.1016/j .bbi.2008.08.001
- Frye RE, Delhey L, Slattery J, Tippett M, Wynne R, Rose S, et al. Blocking and binding folate receptor alpha autoantibodies identify novel autism spectrum disorder subgroups. Front Neurosci (2016) 10:80. doi: 10.3389/ fnins.2016.00080
- Frye RE, Slattery J, Delhey L, Furgerson B, Strickland T, Tippett M, et al. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry (2018) 23(2):247-56. doi: 10.1038/mp.2016.168
- Burger BJ, Rose S, Bennuri SC, Gill PS, Tippett ML, Delhey L, et al. Autistic siblings with novel mutations in two different genes: insight for genetic workups of autistic siblings and connection to mitochondrial dysfunction. Front Pediatr (2017) 5:219. doi: 10.3389/fped.2017.00219
- Delhey L, Kilinc EN, Yin L, Slattery J, Tippett M, Wynne R, et al. Bioenergetic variation is related to autism symptomatology. Metab Brain Dis (2017) 32(6):2021-31. doi: 10.1007/s11011-017-0087-0
- Delhey LM, Nur Kilinc E, Yin L, Slattery JC, Tippett ML, Rose S, et al. The effect of mitochondrial supplements on mitochondrial activity in children with autism spectrum disorder. J Clin Med (2017) 6(2):pii:E18. doi: 10.3390/ jcm6020018
- Frye RE, Wynne R, Rose S, Slattery J, Delhey L, Tippett M, et al. Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder. J Neuroendocrinol (2017) 29(3) :1-12. doi: 10.1111/jne.12461
- Delhey LM, Tippett M, Rose S, Bennuri SC, Slattery JC, Melnyk S, et al. Comparison of treatment for metabolic disorders associated with autism:reanalysis of three clinical trials. Front Neurosci (2018) 12:19. doi: 10.3389/fnins.2018.00019
- Howsmon DP, Vargason T, Rubin RA, Delhey L, Tippett M, Rose S, et al. Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: a comparison and validation study. Bioeng Transl Med (2018) 3(2):156-65. doi: 10.1002/ btm2.10095
- Vargason T, Kruger U, Roth E, Delhey LM, Tippett M, Rose S, et al. Comparison of three clinical trial treatments for autism spectrum disorder through multivariate analysis of changes in metabolic profiles and adaptive behavior. Front Cell Neurosci (2018) 12:503. doi: 10.3389/fncel.2018.00503
- Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Melnyk S, et al. Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines. Transl Psychiatry (2014) 4:e377. doi: 10.1038/ tp.2014.15
- Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Pavliv O, et al. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort. PLoS One (2014) 9(1):e85436. doi: 10.1371/journal.pone.0085436
- Rose S, Bennuri SC, Wynne R, Melnyk S, James SJ, Frye RE. Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling control study. FASEB J (2017) 31(3):904-9. doi: 10.1096/fj.201601004R
- Bennuri SC, Rose S, Frye RE. Mitochondrial dysfunction is inducible in lymphoblastoid cell lines from children with autism and may involve the TORC1 pathway. Front Psychiatry (2019) 10:269. doi: 10.3389/fpsyt.2019.00269
- Rose S, Wynne R, Frye RE, Melnyk S, James SJ. Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines. J Toxicol (2015) 2015:573701. doi: 10.1155/2015/573701
- Frye RE, Rose S, Chacko J, Wynne R, Bennuri SC, Slattery JC, et al. Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Transl Psychiatry (2016) 6(10):e927. doi: 10.1038/tp.2016.189
- Frye RE, Rose S, Wynne R, Bennuri SC, Blossom S, Gilbert KM, et al. Oxidative stress challenge uncovers trichloroacetaldehyde hydrate-induced mitoplasticity in autistic and control lymphoblastoid cell lines. Sci Rep (2017) 7(1):4478. doi: 10.1038/s41598-017-04821-3
- Rose S, Bennuri SC, Davis JE, Wynne R, Slattery JC, Tippett M, et al. Butyrate enhances mitochondrial function during oxidative stress in cell lines from boys with autism. Transl Psychiatry (2018) 8(1):42. doi: 10.1038/ s41398-017-0089-z
- Frye RE, Nankova B, Bhattacharyya S, Rose S, Bennuri SC, MacFabe DF. Modulation of immunological pathways in autistic and neurotypical lymphoblastoid cell lines by the enteric microbiome metabolite propionic acid. Front Immunol (2017) 8:1670. doi: 10.3389/fimmu.2017.01670
- Harville TO. “HLA typing for cellular product characterization and identity testing,”. In: EllenAreman MM, Loper K, editors. Cellular Therapy: Principles, Methods, and Regulations. AABB (2016).
- Batra A, Cottler-Fox M, Harville T, Rhodes-Clark BS, Makhoul I, Nakagawa M. Autologous graft versus host disease: an emerging complication in patients with multiple myeloma. Bone Marrow Res (2014) 2014:891427. doi: 10.1155/ 2014/891427
- Jyonouchi H, Geng L, Streck DL, Dermody JJ, Toruner GA. MicroRNA expression changes in association with changes in interleukin-1ss/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study). J Neuroinflammation (2017) 14(1):229. doi: 10.1186/s12974-017-1003-6
- Jyonouchi H, Geng L, Streck DL, Toruner GA. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflammation (2012) 9:4. doi: 10.1186/1742-2094-9-4
- “Human leukocyte antigens (HLAs) can be found on the surface of most cells of the body. They are a method of categorising one's 'tissue type' and they play a role in determining a person's immune response to foreign substances
[00:54] Welcome back Mark Donohoe
[01:26] What is Human Leukocyte Antigen (HLA)
[05:34] The changing clinical significance of HLA
[08:36] Immunology and reproduction
[10:22] Genetic diversity
[13:21] HLA subtypes: mould and mycotoxins
[18:50] HLA inheritance
[20:50] Clinical value in screening
[40:32] Diseases/Disorders relevant to HLA
[46:34] Medicine interfering in evolution
[49:56] HLA and thyroid disorders
[54:36] Psoriasis and delayed drug reactions
[1:01:14] Determining when to screen for HLA?
[1:03:45] Final summary and resources
Significant Association of HLA-B Alleles and Genotypes in Thai Children with Autism Spectrum Disorders: A Case-Control Study
Disease Markers, Volume 2015, Article ID 724935, 7 pages. http://dx.doi.org/10.1155/2015/724935 FREE PDF
Apichaya Puangpetch,1,2 Pongwut Suwannarat,1,2 Montri Chamnanphol,1,2 Napatrupron Koomdee,1,2 Nattawat Ngamsamut,3 Penkhae Limsila,3 and Chonlaphat Sukasem1,2
Autism is a severe neurodevelopmental disorder. Many susceptible causative genes have been identified. Most of the previous reports showed the relationship between the Human Leukocyte Antigen (HLA) gene and etiology of autism. In order to identify HLA-B alleles associated with autism in Thai population, we compared the frequency of HLA-B allele in 364 autistic subjects with 952 normal subjects by using a two-stage sequence-specific oligonucleotide probe system (PCR-SSOP) method based on flow- cytometry technology. HLA-B'13:02 (P = 0.019, OR = 2.229), HLA-B'38:02 (P = 0.049, OR = 1.628), HLA-B'44:03 (P = 0.016, OR = 1.645), and HLA-B'56:01 (P = 1.78 x 10-4, OR = 4.927) alleles were significantly increased in autistic subjects compared with normal subjects. Moreover, we found that the HLA-B' 18:02 (P = 0.016, OR = 0.375) and HLA-B'46:12 (P = 0.008, OR = 0.147) alleles were negatively associated with autism when compared to normal controls. Both alleles might have a protective role in disease development. In addition, four HLA-B genotypes of autistic patients had statistically significant relationship with control groups, consisting of HLA-B'3905/'5801 (P = 0.032, OR = 24.697), HLA-B'2704/'5801 (P = 0.022, OR = 6.872), HLA-B'3501/'4403 (P = 0.021, OR = 30.269), and HLA-B' 1801/'4402 (P = 0.017, OR = 13.757). This is the first report on HLA-B associated with Thai autism and may serve as a marker for genetic susceptibility to autism in Thai population.
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- “Stubbs & Magenis (1980) first suggested over 30 years ago that the human leukocyte antigen (HLA) region might be involved in autism”
Wonder if there has been an increase some diseases due to poor HLA genes being passed on to children?
Before: Autism, Leishmaniasis, Vitiligo, Graves' disease, celiac disease, ankylosing spondylitis, T1 diabetes, myasthenia gravis, Sjögren syndrome, thyroiditis, etc. would not be inherited, but now it is a possibility.