HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review

Schmidt, Hollie; Williamson, Dhelia; Ashley-Koch, Allison

doi:10.1093/aje/kwk118

Cited by 212Multiple Sclerosis Research StudiesGenetic Associations and EpidemiologyPsoriasis: Treatment and Pathogenesis

HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review

Schmidt, Hollie, Williamson, Dhelia, Ashley-Koch, Allison·2007·American Journal of Epidemiology

DOI 10.1093/aje/kwk118

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Abstract

An association between multiple sclerosis (MS) and the human leukocyte antigen (HLA) complex, a dense cluster of genes on the short arm of chromosome 6, was first noted over 30 years ago. In Caucasian populations of Northern European descent, the DR15 haplotype (DRB1*1501-DQA1*0102-DQB1*0602) has been hypothesized to be the primary HLA genetic susceptibility factor for MS. However, studies of other populations have produced varying results. Thus, the authors reviewed the literature for articles on the association between the DR15 haplotype and MS. They identified 72 papers meeting the inclusion criteria: human genetic studies written in English that were published between 1993 and 2004 and that reported allele frequencies for HLA-DRB1*1501, HLA-DQA1*0102, or HLA-DQB1*0602 or the frequency of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. Most of the studies identified used a case-control design (n = 60), while the remainder used a family-based design (n = 22). In most of these papers, investigators reported a higher frequency of the DR15 haplotype and/or its component alleles among MS cases than among controls. However, the authors' confidence in these results is tempered by factors related to study design that may have biased the outcomes.

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The DR15 haplotype and its component alleles also associate with protection against diabetes, a high risk for multiple sclerosis, and risk or protective effects with many other immune-mediated diseases.
“the DR15 haplotype and its component alleles also associate with protection against diabetes108, a high risk for multiple sclerosis109,110, and risk or protective effects with many other immune-mediated diseases”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [110]
A specific class II HLA-DR haplotype, DR15, has been suggested to impart risk for both AD and MS.
“Beyond these findings, a specific class II human leukocyte antigen (HLA)-DR haplotype, DR15, has been suggested to impart risk for both AD and MS (7, 8).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [7]

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Modes of Action of HLA-DR Susceptibility Specificities in Multiple Sclerosis
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The HLA‐DQ(α1*0102, β1*0602) heterodimer may confer susceptibility to multiple sclerosis in the absence of the HLA‐DR(α1*01, β1*1501) heterodimer
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Evidence for Linkage Disequilibrium Between HLA-DRB1 Gene and Multiple Sclerosis
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Mapping of a susceptibility gene for multiple sclerosis to the 51 kb interval between G511525 and D6S1666 using a new method of haplotype sharing analysis
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Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DRβ1 chain in multiple sclerosis
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Genomic HLA profiles of MS in Hokkaido, Japan: important role of DPB1*0501 allele
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Epidemiology of multiple sclerosis in Arabs in Jordan: a comparative study between Jordanians and Palestinians
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HLA‐DQA1 and ‐DQB1 associations with multiple sclerosis in Sardinia and French Canada
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Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland
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An investigation of HLA‐encoded genetic susceptibility to multiple sclerosis in subjects of Asian Indian and Afro‐Caribbean ethnic origin
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Intercellular adhesion molecule-1: a protective haplotype against multiple sclerosis
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Histocompatibility antigen (HLA) associations with multiple sclerosis in Iran
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HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: No evidence for disease association with the T-cell receptor
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HLA‐DPB1 alleles correlate with risk for multiple sclerosis in Caucasoid and Cantonese patients lacking the high‐risk DQB1*0602 allele
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A case-control study of chronic neuropsychiatric disease and organic solvent exposure in automobile assembly plant workers.
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Organic solvents and multiple sclerosis: a case-control study
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Clinical infections and multiple sclerosis: contribution from analytical epidemiology.
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Multiple sclerosis associated amino acids of polymorphic regions relevant for the HLA antigen binding are confined to HLA-DR2
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Genetic susceptibility to multiple sclerosis in a Shanghai Chinese population the role of the HLA Class II genes
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Molecular typing of human leukocyte antigen and related polymorphisms following whole genome amplification
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HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients
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HLA‐DQ polymorphisms do not explain HLA class II associations with multiple sclerosis in two Canadian patient groups
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The combination of HLA-DR1 and HLA-DR53 protects against MS
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Additive effect of the HLA-DR15 haplotype on susceptibility to multiple sclerosis
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Role of Predisposing and Protective HLA-DQA and HLA-DQB Alleles in Sardinian Multiple Sclerosis
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Obstacles to identifying viruses that cause autoimmune disease
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Multiple sclerosis in the tropics: genetic association to STR’s loci spanning the HLA and TNF
Palacio, L. G., Rivera, D., Builes, J. J., Jiménez, M. E., Salgar, M., Anaya, J., Jiménez, I., Camargo, M., Arcos‐Burgos, M., & Sánchez, J. L. (2002) · Multiple Sclerosis Journal · doi:10.1191/1352458502ms804oa · Cited by 23 · see citing works
The HLA-DR13 haplotype is associated with “benign” multiple sclerosis in northeast Italy
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HLA Typing in Acute Optic Neuritis
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Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians
Guerini, F. R., Ferrante, P., Losciale, L., Caputo, D., Lombardi, M. L., Pirozzi, G., Luongo, V., Sudomoina, M. A., Andreewski, T. V., Alekseenkov, A. D., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000079372.54703.a8 · Cited by 21 · see citing works
Study of HLA as a Predisposing Factor and Its Possible Influence on the Outcome of Multiple Sclerosis in the Sanitary District of Calatayud, Northern Spain
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The association between multiple sclerosis and infection with Epstein-Barr virus and retrovirus.
HAAHR, S., & Munch, M. (2000) · PubMed · Cited by 21 · see citing works
Evidence of Linkage between Susceptibility to Multiple Sclerosis and HLA-Class II Loci in Italian Multiplex Families
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DR2/DQwl Inheritance and haplotype sharing in affected siblings from multiple sclergis families
Voskuhl, R. R., Goldstein, A. M., Voskuhl, T., Davey, R. J., & McFarland, H. F. (1996) · Annals of Neurology · doi:10.1002/ana.410390618 · Cited by 20 · see citing works
ANALYSIS OF HLA‐CLASS II DQA1, DQB1, DRB1 and DPB1 IN ITALIAN MULTIPLE SCLEROSIS PATIENTS
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Clinico-immunogenetic characteristics of multiple sclerosis with optic neuritis in children.
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The DRB1 Val86/Val86genotype associates with multiple sclerosis in Australian patients
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Distribution of HLA-Dw2 in optic neuritis and multiple sclerosis indicates heterogeneity
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Evidence for the genetic role of human leukocyte antigens in low frequency DRBI*1501 multiple sclerosis patients in Israel
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Multiple Sclerosis: Association to HLA DQα in a Tropical Population
Arcos‐Burgos, M., Palacio, G., Sánchez, J. L., Londoño, A. C., Uribe, C. S., Jiménez, M. E., Villa, A., Anaya, J., Bravo, M. L. J., Jaramillo, N., et al. (1999) · Experimental and Clinical Immunogenetics · doi:10.1159/000019105 · Cited by 14 · see citing works
Multiple sclerosis in the Faroe Islands VI. Studies of HLA markers
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HLA-DM polymorphisms do not associate with multiple sclerosis: an association study with analysis of myelin basic protein T cell specificity
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The fine specificity of human T cell lines towards myelin basic protein peptides in southern italian multiple sclerosis patients
Montanaro, D., Sanna, V., Matarese, G., Larby, B. B., Racioppi, L., Carrieri, P. B., Bruno, R., Davey, N. J., Zappacosta, S., & Fontana, S. (2001) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2001.01457.x · Cited by 13 · see citing works
Multiple Sclerosis, Solvents, and Pets
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Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel
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Involvement ofBRCA1 andBRCA2 in breast cancer in a western Finnish sub-population
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T cell receptor β chain genotyping in Australian relapsing-remitting multiple sclerosis patients
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HLA class II susceptibility and resistance genes in patients with multiple sclerosis from northern Spain, by DNA-RFLP genotyping.
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Viral antibody titers, immunogenetic markers, and their interrelations in multiple sclerosis patients and controls
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Lack of evidence for a role of the myelin basic protein gene in multiple sclerosis susceptibility in Sardinian patients
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Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure
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Untitled work
Cann, S. A. H., Netten, J. P. V., & Netten, C. V. (2000) · Pure Amsterdam UMC · doi:10.1002/1531-8249(200003)47:3
Untitled work
Khan (2000) · doi:10.1002/1531-8249(200008)48:2

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Sorted by citations

Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
The HLA genomic loci map: expression, interaction, diversity and disease
Shiina, T., Hosomichi, K., Inoko, H., & Kulski, J. K. (2009) · Journal of Human Genetics · doi:10.1038/jhg.2008.5 · Cited by 788 · see citing works
Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis
Simpson, S., Blizzard, L., Otahal, P., Van der Mei, I., & Taylor, B. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2011.240432 · Cited by 718 · see citing works
Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential
Dankers, W., Colin, E. M., van Hamburg, J. P., & Lubberts, E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00697 · Cited by 453 · see citing works
Body size and risk of MS in two cohorts of US women
Munger, K. L., Chitnis, T., & Ascherio, A. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c0d6e0 · Cited by 441 · see citing works
The immunogenetics of multiple sclerosis: A comprehensive review
Hollenbach, J. A., & Oksenberg, J. R. (2015) · Journal of Autoimmunity · doi:10.1016/j.jaut.2015.06.010 · Cited by 423 · see citing works
“A HuGE (Human Genome Epidemiology) review of 72 papers published from 1993–2004 found that in all but a very few studies, the frequency of DRB1*15:01 was greater in cases than controls, and that this was by a wide margin the most consistent finding [41].”
Background
Th17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis
Jadidi‐Niaragh, F., & Mirshafiey, A. (2011) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2011.02536.x · Cited by 389 · see citing works
The initiation and prevention of multiple sclerosis
Ascherio, A., Munger, K. L., & Lünemann, J. D. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.198 · Cited by 288 · see citing works
Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms
O’Gorman, C., Lucas, R. M., & Taylor, B. V. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911718 · Cited by 209 · see citing works
“Associations between HLA-DR15 haplotype (the DRB1*1501 allele and the alleles with which it is in linkage disequilibrium: DQA1*0102, and DQB1*0602) and MS have been described throughout European and non-European populations with MS [34].”
Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies
Vlam, L., van der Pol, W. L., Cats, E. A., Straver, D. C. G., Piepers, S., Franssen, H., & van den Berg, L. H. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.175 · Cited by 207 · see citing works
Environmental risk factors for multiple sclerosis
Salzer, J. (2013) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 202 · see citing works
Anti-Epstein–Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel
Munger, K. L., Levin, L., O’Reilly, É., Falk, K. I., & Ascherio, A. (2011) · Multiple Sclerosis Journal · doi:10.1177/1352458511408991 · Cited by 200 · see citing works
“The association that we found between anti-EBNA antibodies and MS risk is unlikely to reflect confounding by genetic factors because we have previously shown that the HLADRB1*1501 allele, which is the strongest genetic predictor of MS [12], and anti-EBNA titers contribute independently and multiplicatively to MS risk.”
Result
International Encyclopedia of Rehabilitation
Tower, K. (2010) · Cited by 173 · see citing works
Biomarkers in Multiple SclerosisPreprint
Paul, A., Comabella, M., & Gandhi, R. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029058 · Cited by 157 · see citing works
“More recent investigations, conducted in many MS cohorts, suggested that the allele mainly responsible for attributing genetic risk in MS population is the HLADRB1 1501 (al-Din et al. 1995; Kwon et al. 1999; Bozikas et al. 2003; Oksenberg et al. 2004; Schmidt et al. 2007).”
Background
Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target
Liu, R., Du, S., Zhao, L., Jain, S., Sahay, K., Rizvanov, A. A., Lezhnyova, V., Хайбуллин, Т. И., Martynova, E. V., Khaiboullina, S. F., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.996469 · Cited by 153 · see citing works
“Also finding the link between Human leukocyte Antigen (HLA) DRB1*1501 haplotype and MS in Northern European populations supported this assumption (37).”
Background
Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities
Miljković, D. M., & Spasojević, I. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.5068 · Cited by 136 · see citing works
“The latter might explain why a higher frequency of HLA-DRB1 *15 is detected in MS patients in Scandinavian countries compared with those in Mediterranean countries, or those in some other non-European countries (391).”
Biomarkers in Multiple Sclerosis: An Up-to-Date Overview
Katsavos, S., & Anagnostouli, M. C. (2013) · Multiple Sclerosis International · doi:10.1155/2013/340508 · Cited by 100 · see citing works
“MS cohorts, made clear that HLA-DRB11501 is the mainly responsible allele for attributing genetic risk in MS population [17–21].”
Background
Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis
Pierrot‐Deseilligny, C., & Souberbielle, J. (2013) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285612473513 · Cited by 97 · see citing works
Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case–control study
Steele, N. Z. R., Carr, J. S., Bonham, L. W., Geier, E. G., Damotte, V., Miller, Z. A., Desikan, R. S., Boehme, K. L., Mukherjee, S., Crane, P. K., et al. (2017) · PLOS Medicine · doi:10.1371/journal.pmed.1002272 · Cited by 91 · see citing works
Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population
Deschamps, R., Paturel, L., Jeannin, S., Chausson, N., Olindo, S., Béra, O., Bellance, R., Smadja, D., Césaire, D., & Cabre, P. (2010) · Multiple Sclerosis Journal · doi:10.1177/1352458510382810 · Cited by 91 · see citing works
The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease
Bonham, L. W., Sirkis, D. W., & Yokoyama, J. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01170 · Cited by 83 · see citing works
Regenerating Immunotolerance in Multiple Sclerosis with Autologous Hematopoietic Stem Cell Transplant
Massey, J. C., Sutton, I. J., Ma, D. D. F., & Moore, J. J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00410 · Cited by 80 · see citing works
The immunogenetics of neurological disease
Misra, M. K., Damotte, V., & Hollenbach, J. A. (2018) · Immunology · doi:10.1111/imm.12869 · Cited by 74 · see citing works
Origins and immunopathogenesis of autoimmune central nervous system disorders
Ramanathan, S., Brilot, F., Irani, S. R., & Dale, R. C. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00776-4 · Cited by 71 · see citing works
Ethnicity and prevalence of multiple sclerosis in east London
Albor, C., du Sautoy, T., Vanan, N. K., Turner, B. P., Boomla, K., & Schmierer, K. (2016) · Multiple Sclerosis Journal · doi:10.1177/1352458516638746 · Cited by 66 · see citing works
Relationship between HLA-DRB1 polymorphism and susceptibility or resistance to multiple sclerosis in Caucasians: A meta-analysis of non-family-based studies
Zhang, Q., Lin, C., Dong, Q., Wang, J., & Wang, W. (2011) · Autoimmunity Reviews · doi:10.1016/j.autrev.2011.03.003 · Cited by 61 · see citing works
Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis
Cox, M., Ban, M., Bowden, N. A., Baker, A., Scott, R. J., & Lechner‐Scott, J. (2011) · Multiple Sclerosis Journal · doi:10.1177/1352458511415562 · Cited by 60 · see citing works
“investigations, the HLA-DRB1*1501 allele has remained the strongest genetic risk factor for developing MS.(3) A recent meta-analysis of GWAS data identified rs3135388, the tagging SNP of DRB1*1501, as the most significantly associated SNP in MS (p 1⁄4 3.”
Background
The HLA Class II Allele DRB1*1501 Is Over-Represented in Patients with Idiopathic Pulmonary Fibrosis
Xue, J., Gochuico, B. R., Alawad, A. S., Feghali‐Bostwick, C. A., Noth, I., Nathan, S. D., Rosen, G., Rosas, I. O., Đačić, S., Ocak, İ., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014715 · Cited by 58 · see citing works
“were several-fold less than that measured here, and were also much less than frequencies reported within other large Caucasian control populations”
Result
A meta-analysis of interaction between Epstein-Barr virus and HLA-DRB1*1501 on risk of multiple sclerosis
Xiao, D., Ye, X., Zhang, N., Ou, M., Guo, C., Zhang, B., Liu, Y., Wang, M., Yang, G., & Jing, C. (2015) · Scientific Reports · doi:10.1038/srep18083 · Cited by 57 · see citing works
Genome-wide association study identifies five risk loci for pernicious anemia
Laisk, T., Lepamets, M., Koel, M., Abner, E., Metspalu, A., Nelis, M., Milani, L. A., Esko, T., & Mägi, R. (2021) · Nature Communications · doi:10.1038/s41467-021-24051-6 · Cited by 53 · see citing works
The role of polymorphic ERAP1 in autoinflammatory disease
Reeves, E., & James, E. (2018) · Bioscience Reports · doi:10.1042/bsr20171503 · Cited by 55 · see citing works
EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis: a case-control study
Sundström, P., Nyström, L., Jidell, E., & Hallmans, G. (2008) · Multiple Sclerosis Journal · doi:10.1177/1352458508092353 · Cited by 55 · see citing works
“The HLA class II haplotype DR 15 is the best studied genetic risk factor for MS and most studies on its alleles have addressed DRB1*1501 [1].”
Background
“Plasma Cell Hepatitis” in Liver Allografts: Identification and Characterization of an IgG4-Rich Cohort
Castillo‐Rama, M., Sebagh, M., Sasatomi, E., Randhawa, P. S., Isse, K., Salgarkar, A. D., Ruppert, K. M., Humar, A., & Demetris, A. J. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12413 · Cited by 54 · see citing works
“Additionally, it is also described in multiple sclerosis where increased production of plasma cells and oligoclonal IgG4 bands are seen (43,44).”
Background
Reduced thymic output and peripheral naïve CD4 T-cell alterations in primary progressive multiple sclerosis (PPMS)
Haegert, D. G., Hackenbroch, J., Duszczyszyn, D. A., Fitz-Gerald, L., Zastepa, E., Mason, H., Lapierre, Y., Antel, J. P., & Bar‐Or, A. (2011) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.12.007 · Cited by 52 · see citing works
“Thus, it seems unlikely that the DR15-hapolotype (Schmidt et al., 2007) can explain our findings in RRMS or PPMS.”
Result
Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future
Raphael, I., Webb, J., Stüve, O., Haskins, W. E., & Forsthuber, T. G. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2015.991315 · Cited by 51 · see citing works
“The strongest genetic link for MS susceptibility was established with the genes of the HLA-DR15 haplotype [76].”
Background
Understanding Progressive Multifocal Leukoencephalopathy Risk in Multiple Sclerosis Patients Treated with Immunomodulatory Therapies: A Bird’s Eye View
Mills, E. A., & Mao‐Draayer, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00138 · Cited by 51 · see citing works
“HLA-DRB1*15 is the most well-established susceptibility allele for MS (204), but may confer protection against JCV.”
Background
Dendritic cells in central nervous system autoimmunity
Sie, C., & Korn, T. (2016) · Seminars in Immunopathology · doi:10.1007/s00281-016-0608-7 · Cited by 47 · see citing works
“It is well established that certain genetic variations inMHC class II molecules on the surface of professional APCs are associated with the disease, most prominently the HLA haplotype DRB1*15:01 in humans [2].”
Background
Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
Guha, S., Rosenfeld, J., Malhotra, A. K., Lee, A. T., Gregersen, P. K., Kane, J. M., Pe’er, I., Darvasi, A., & Lencz, T. (2012) · Genome biology · doi:10.1186/gb-2012-13-1-r2 · Cited by 47 · see citing works
“This allele has been associated with susceptibility to multiple sclerosis and other autoimmune diseases [38].”
Background
Coexisting narcolepsy (with and without cataplexy) and multiple sclerosis
Kallweit, U., Bassetti, C. L., Oberholzer, M., Fronczek, R., Béguin, M., Strub, M., & Lammers, G. J. (2018) · Journal of Neurology · doi:10.1007/s00415-018-8949-x · Cited by 46 · see citing works
Prostaglandins in pathogenesis and treatment of multiple sclerosis
Mirshafiey, A., & Jadidi‐Niaragh, F. (2010) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923971003667627 · Cited by 44 · see citing works
Multiple sclerosis associates with LILRA3 deletion in Spanish patients
Ordóñez, D., Sánchez, A., Rodríguez, J., Cisneros, E., Ramil, E., Romo, N., Moraru, M., Munteis, E., López‐Botet, M., Roquer, J., et al. (2009) · Genes and Immunity · doi:10.1038/gene.2009.34 · Cited by 45 · see citing works
HLA-DRB1⁎15 and cerebrospinal-fluid-specific oligoclonal immunoglobulin G bands lower age at attainment of important disease milestones in multiple sclerosis
Imrell, K., Greiner, E., Hillert, J. A., & Masterman, T. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.03.005 · Cited by 43 · see citing works
“Although here, as elsewhere (reviewed in Schmidt et al., 2007), carriage of HLADRB1⁎15 lowered age in MS onset, the allele's effect on age at EDSS 6.0 remained statistically significant after inclusion of onset age in model 1 of Table 2 (HR=1.23 [95% CI, 1.03–1.48; p=0.026]).”
Influential
Network analysis of genes and their association with diseases
Kontou, P. I., Pavlopoulou, A., Dimou, N. L., Pavlopoulos, G. A., & Bagos, P. G. (2016) · Gene · doi:10.1016/j.gene.2016.05.044 · Cited by 41 · see citing works
Immune-mediated genesis of multiple sclerosis
Cavallo, S. (2020) · Journal of Translational Autoimmunity · doi:10.1016/j.jtauto.2020.100039 · Cited by 41 · see citing works
“HLA-DRB1*15:01 has the strongest effect with an average odds (OR) ratio of 3,08 and an additional risk in homozygous subjects [6].”
Background
The Role of HLA DR-DQ Haplotypes in Variable Antibody Responses to Anthrax Vaccine Adsorbed
Pajewski, N., Parker, S. D., Poland, G., Ovsyannikova, I., Song, W.-Z., Zhang, K., McKinney, B., Pankratz, V., Edberg, J., Kimberly, R., et al. (2011) · Genes and Immunity · doi:10.1038/gene.2011.15 · Cited by 35 · see citing works
Microarray-Based Detection of CYP1A1, CYP2C9, CYP2C19, CYP2D6, GSTT1, GSTM1, MTHFR, MTRR, NQO1, NAT2, HLA-DQA1, and AB0 Allele Frequencies in Native Russians
Gra, O., Mityaeva, O., Berdichevets, I., Kozhekbaeva, Z. M., Fesenko, D., Kurbatova, O., Goldenkova-Pavlova, I., & Nasedkina, T. (2010) · Genetic Testing and Molecular Biomarkers · doi:10.1089/gtmb.2009.0158 · Cited by 35 · see citing works
“…role in many autoimmune disorders, such as multiple sclerosis, psoriasis, type 1 diabetes, rheumatoid arthritis, celiac disease, and others (Laivoranta-Nyman et al ., 2004; Zhang et al ., 2004; Schmidt et al ., 2007; Erlich et al ., 2008; Monsuur et al ., 2008; Resic-Lindehammer et al ., 2008).”
Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors
Thewissen, K., Nuyts, A. H., Deckx, N., Wijmeersch, B. V., Nagels, G., D'hooghe, M. B., Willekens, B. M. P., Cras, P. P., Eijnde, B. O., Goossens, H., et al. (2013) · Multiple Sclerosis Journal · doi:10.1177/1352458513505352 · Cited by 39 · see citing works
Analysis of HLA DR2&DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) Haplotypes in Iranian Patients with Multiple Sclerosis
Ghabaee, M., Bayati, A., Saroukolaei, S. A., Sahraian, M. A., Sanati, M. H., Karimi, P., Houshmand, M., Sadeghian, H., & Chelavi, L. H. (2008) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-008-9302-1 · Cited by 39 · see citing works
“Inconsistent results were obtained between HLA class II alleles and clinical characteristics of MS ( Schmidt et al. 2007 ); some studies found DRB1* 1501 to be associated with a younger age at onset (Hensiek et al. 2002; Smestad et al. 2007) and others did not (Amirzargar et al. 1998; Ballerini et al. 2004).”
Result
HLA‐DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population
Romero-Pinel, L., Pujal, J. M., Martínez‐Yélamos, S., Gubieras, L., Matas, E., Bau, L., Torrabadella, M., Azqueta, C., & Arbizu, T. (2010) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.03148.x · Cited by 33 · see citing works
“This association has been already well established in most studied cohorts and specially the Caucasian populations [13].”
Background
Hypomorphic MGAT5 polymorphisms promote multiple sclerosis cooperatively with MGAT1 and interleukin-2 and 7 receptor variants
Li, C. F., Zhou, R. W., Mkhikian, H., Newton, B. L., Yu, Z., & Demetriou, M. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.12.008 · Cited by 33 · see citing works
“…response, such as the major histocompatibility complex locus (HLA) and interleukin receptors IL2RA and IL7RA (Gregory et al., 2007; Lundmark et al., 2007; Schmidt et al., 2007; Maier et al., 2009a,b; *Corresponding author at: Department of Neurology, University of California, Irvine, CA 92869, USA.”
Genetics of experimental allergic encephalomyelitis supports the role of T helper cells in multiple sclerosis pathogenesis
Blankenhorn, E. P., Butterfield, R. J., Case, L. K., Wall, E. H., del Río, R., Diehl, S. A., Krementsov, D. N., Saligrama, N., & Teuscher, C. (2011) · Annals of Neurology · doi:10.1002/ana.22642 · Cited by 32 · see citing works
“The heritability of MS is estimated to be 35%, largely associated with the inheritance of susceptible HLA haplotypes that can be present in up to 70% of these MS cases.(2) However, polymorphisms in many other genes have also been associated with MS in genome-wide association studies (GWAS).”
Background
Small Molecule Inhibitor of Antigen Binding and Presentation by HLA-DR2b as a Therapeutic Strategy for the Treatment of Multiple Sclerosis
Ji, N., Somanaboeina, A., Dixit, A., Kawamura, K., Hayward, N. J., Self, C. R., Olson, G. L., & Forsthuber, T. G. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300407 · Cited by 32 · see citing works
“In those MS patients who express the DR2b gene [∼60% of all MS patients (23)], selectively blocking this target is expected to disrupt the autoimmune process but not generally compromise the immune system.”
Background
The tag SNP for HLA-DRB1⁎1501, rs3135388, is significantly associated with multiple sclerosis susceptibility: Cost-effective high-throughput detection by real-time PCR
Živković, M., Stanković, A., Dinčić, E., Popović, M., Popovic, S., Raičević, R., & Alavantić, D. (2009) · Clinica Chimica Acta · doi:10.1016/j.cca.2009.05.004 · Cited by 31 · see citing works
Endosomal Toll-Like Receptors Mediate Enhancement of Interleukin-17A Production Triggered by Epstein-Barr Virus DNA in Mice
Shehab, M., Sherri, N., Hussein, H. M., Salloum, N. A., & Rahal, E. A. (2019) · Journal of Virology · doi:10.1128/jvi.00987-19 · Cited by 30 · see citing works
“This association has been reported in Caucasian populations (17).”
Background
HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country, Spain)
Fernández, Ó., Antigüedad, A. R., Pinto-Medel, M. J., Mendibe, M. M., Acosta, N., Oliver‐Martos, B., Guerrero, M., Papais-Alvarenga, M., Fernández-Sánchez, V. E., & Leyva, L. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5223-2 · Cited by 30 · see citing works
“Predisposition to MS in Northern European, American and African-American subjects has been most consistently associated with the HLA-DRB1*1501, DQA1*0102, DQB1*0602 haplotype [32, 33, 73 ] or the HLA-DRB1*15 alleles independent of DQB1*0602 [61].”
Background
Major histocompatibility complex (MHC) associations with diseases in ethnic groups of the Arabian Peninsula
Alnaqbi, H., Mawart, A., Alshamsi, J., AlSafar, H. S., & Tay, G. K. (2021) · Immunogenetics · doi:10.1007/s00251-021-01204-x · Cited by 31 · see citing works
Increased frequency of HLA-DRB1*15 in patients with multifocal motor neuropathy
Sutedja, N. A., Otten, H. G., Cats, E. A., Piepers, S., Veldink, J. H., van der Pol, W. L., & van den Berg, L. H. (2010) · Neurology · doi:10.1212/wnl.0b013e3181d3e2f6 · Cited by 29 · see citing works
HLA-DRB1 allele heterogeneity influences multiple sclerosis severity as well as risk in Western Australia
Wu, J.-S., JAMES, I. R., Qiu, W., Castley, A. S. L., Christiansen, F., Carroll, W. M., Mastaglia, F. L., & Kermode, A. G. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.11.015 · Cited by 29 · see citing works
“Among the over 600 HLA-DRB1 alleles sequenced to date, the dominant association iswith theHLA-DRB1⁎1501allelewhich is found in over 50% of MS cases in all Caucasian populations so far studied (Schmidt et al., 2007) and which is more likely to be transmitted through the maternal line (Ramagopalan et al.”
HLA‐DRB1 and multiple sclerosis in Argentina
Patrucco, L., Larriba, J., Redal, M. A., Rojas, J. I., Argibay, P. F., & Cristiano, E. (2009) · European Journal of Neurology · doi:10.1111/j.1468-1331.2008.02523.x · Cited by 29 · see citing works
“The results of our study are in accordance with other Caucasian MS surveys that have found that HLADRB1*15 allele is strongly associated with MS disease [1,3,5] (Table 2).”
Result
Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk
Nolan, D. A., Castley, A. S. L., Tschochner, M., JAMES, I. R., Qiu, W., Sayer, D. C., Christiansen, F., Witt, C. S., Mastaglia, F. L., Carroll, W. M., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e318263c407 · Cited by 28 · see citing works
Association of HLA-DRB1*1501 tagging rs3135388 gene polymorphism with multiple sclerosis
Benešová, Y., Vašků, A., Štourač, P., Hladíková, M., Fiala, A., & Bednařík, J. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.10.014 · Cited by 28 · see citing works
“(Schmidt et al., 2007).”
BackgroundResultInfluential
HLA associations with multiple sclerosis in Greece
Kouri, I., Papakonstantinou, S., Bempes, V., Vasiliadis, H. S., Kyritsis, A. P., & Pelidou, S. (2011) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2011.06.037 · Cited by 28 · see citing works
“Recently, Schmidt et al reviewed 70 papers on the association between the DR15 haplotype andMS and reported a higher frequency of the DR15 haplotype and/or its component alleles among MS cases than among controls [9].”
Immunopharmacological role of the Leukotriene Receptor Antagonists and inhibitors of leukotrienes generating enzymes in Multiple Sclerosis
Mirshafiey, A., & Jadidi‐Niaragh, F. (2010) · Immunopharmacology and Immunotoxicology · doi:10.3109/08923970903283662 · Cited by 28 · see citing works
“Through these genes, there are robust association between the HLA locus and susceptibility to MS [16], particularly DR15 haplotype and three alleles of DR2 haplotype, including DRB1*1501, DRB5*0101 and DQB1*0602 [17–19].”
Background
Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach
Cappa, R. N., Theroux, L. M., & Brenton, J. N. (2017) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2017.07.005 · Cited by 29 · see citing works
HLA DR and DQ alleles and haplotypes associated with clinical response to glatiramer acetate in multiple sclerosis
Dhib-Jalbut, S. S., Valenzuela, R. M., Ito, K., Kaufman, M., Picone, M. A., & Buyske, S. G. (2013) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2013.02.005 · Cited by 27 · see citing works
“Genetic susceptibility in multiple sclerosis (MS) has been inferred from its association with HLA class-II major histocompatibility antigens which control cell mediated immunity (Schmidt et al., 2007).”
BackgroundResult
Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation
Meléndez‐Torres, G. J., Auguste, P., Armoiry, X., Maheswaran, H., Court, R. A., Madan, J. J., Kan, A., Lin, S., Counsell, C. E., Patterson, J. V., et al. (2017) · Health Technology Assessment · doi:10.3310/hta21520 · Cited by 27 · see citing works
Associated autoimmune diseases in patients with multifocal motor neuropathy and their family members
Cats, E. A., Bertens, A. S., Veldink, J. H., van den Berg, L. H., & van der Pol, W. L. (2011) · Journal of Neurology · doi:10.1007/s00415-011-6315-3 · Cited by 27 · see citing works
“We previously found that HLA-DRB1*15 is more prevalent among patients with MMN than in population based controls [15] similar to patients with MS [13].”
Result
The role of ERAP1 in autoinflammation and autoimmunity
Pepelyayeva, Y., & Amalfitano, A. (2019) · Human Immunology · doi:10.1016/j.humimm.2019.02.013 · Cited by 26 · see citing works
Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort
Romero-Pinel, L., Martínez‐Yélamos, S., Bau, L., Matas, E., Gubieras, L., Pujal, J. M., Morandeira, F., Bas, J., & Arbizu, T. (2011) · European Journal of Neurology · doi:10.1111/j.1468-1331.2011.03379.x · Cited by 26 · see citing works
“Multiple sclerosis (MS) is an autoimmune demyelinating complex genetic disease in which the association with the HLA-DR2 haplotype has been well established in most studied populations [1].”
Background
Environmental Factors Related to Multiple Sclerosis in Indian Population
Malli, C., Pandit, L., D’Cunha, A., & Mustafa, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124064 · Cited by 26 · see citing works
“Availability of suitable environmental triggers may determine the prevalence of autoimmune disorders such as MS given that genetic susceptibility is the same in most parts of the world [27].”
Background
The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility
Bahreini, S. A., Jabalameli, M. R., Saadatnia, M., & Zahednasab, H. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.002 · Cited by 26 · see citing works
“Among the suspected susceptibility genes, HLA-DRB1 on chromosome 6p21 is the most remarkable locus contributed to MS genetic susceptibility (Schmidt et al., 2007).”
Background
Peptide mimotopes alter T cell function in cancer and autoimmunity
Slansky, J. E., & Nakayama, M. (2020) · Seminars in Immunology · doi:10.1016/j.smim.2020.101395 · Cited by 25 · see citing works
“Specific HLA alleles and haplotypes provide susceptibility or protection from the disease, such as susceptibility with DQ2 and DQ8 in celiac disease [49–51], DR3-DQ2/ DR4-DQ8 in type 1 diabetes [52–54], DQB1*0602 in narcolepsy [55, 56], and DR15-DQ6 in multiple sclerosis [57, 58].”
Background
Epigenetics in Multiple Sclerosis
Chan, V. S. F. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-3449-2_12 · Cited by 25 · see citing works
Identification of Genetic Determinants of the Sexual Dimorphism in CNS Autoimmunity
Bearoff, F. M., Case, L. K., Krementsov, D. N., Wall, E. H., Saligrama, N., Blankenhorn, E. P., & Teuscher, C. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117993 · Cited by 25 · see citing works
Macrophages and HLA-Class II Alleles in Multiple Sclerosis: Insights in Therapeutic Dynamics
Prapas, P., & Anagnostouli, M. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137354 · Cited by 25 · see citing works
“DRB1*15:01 is often found in combination with DQB1*06:02 and DQA1*01:02 alleles [41]; this combination are risk markers for MS even though their functional role has been controversial.”
Background
Characterization of the major histocompatibility complex class II DOB, DPB1, and DQB1 alleles in cynomolgus macaques of Vietnamese origin
Ling, F., Wei, L., Wang, T., Wang, H., Zhuo, M., Du, H., Wang, J., & Wang, X. (2010) · Immunogenetics · doi:10.1007/s00251-010-0498-0 · Cited by 24 · see citing works
“It has been reported that HLA-DQB1 alleles have been associated as an increased risk of developing type 1 diabetes (Todd 1990; Todd 1997; Redondo et al. 2001), celiac disease (Murray et al. 2007), multiple sclerosis (Dyment et al. 1997; Schmidt et al. 2007, and narcolepsy (Kadotani et al. 1998).”
Background
TNFR2 limits proinflammatory astrocyte functions during EAE induced by pathogenic DR2b-restricted T cells
Raphael, I., Gomez‐Rivera, F., Raphael, R. A., Robinson, R. R., Nalawade, S. A., & Forsthuber, T. G. (2019) · JCI Insight · doi:10.1172/jci.insight.132527 · Cited by 24 · see citing works
“Discussion MS has both genetic and environmental predispositions, including HLA-DR2b (28).”
Background
Immunological tests and their interpretation in uveitis
Rathinam, S., Tuğal-Tutkun, İ., Agarwal, M., Vedhanayaki, R., Egriparmak, M., & Patnaik, G. (2020) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_570_20 · Cited by 22 · see citing works
“[119] Both idiopathic intermediate uveitis (pars planitis) and multiple sclerosis have been found to be associated with the HLA-DR15 subtype of HLA-DR2.”
Background
Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis
Massey, J. C., Jackson, K., Singh, M., Hughes, B., Withers, B., Ford, C., Khoo, M., Hendrawan, K., Zaunders, J. J., Muylder, B. C.-D., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.798300 · Cited by 22 · see citing works
Influence of HLA-DRB1 allele heterogeneity on disease risk and clinical course in a West Australian MS cohort: a high-resolution genotyping study
Wu, J.-S., JAMES, I. R., Qiu, W., Castley, A. S. L., Christiansen, F., Carroll, W. M., Mastaglia, F. L., & Kermode, A. G. (2010) · Multiple Sclerosis Journal · doi:10.1177/1352458510362997 · Cited by 22 · see citing works
“Of the more than 600 alleles so far identified at this locus the HLA-DRB1*1501 allele has been found in over 50% of cases of MS in most Caucasian populations studied.(3) Other alleles associated with an increased risk include HLA-DRB1*0301 (DR3 haplotype, or DR17), which has been reported in several populations,(4,5,6…”
Background
Autoantigens and autoantibodies in multiple sclerosis.
Mirshafiey, A., & Kianiaslani, M. (2013) · PubMed · Cited by 21 · see citing works
Replication analysis of variants associated with multiple sclerosis risk
Dashti, M., Ateyah, K., Alroughani, R., & Al-Temaimi, R. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-64432-3 · Cited by 20 · see citing works
High resolution HLA analysis reveals independent class I haplotypes and amino-acid motifs protective for multiple sclerosis
Mack, S. J., Udell, J. B. M., Cohen, F., Osoegawa, K., Hawbecker, S. K., Noonan, D. A., Ladner, M. B., Goodridge, D., Trachtenberg, E., Oksenberg, J. R., et al. (2018) · Genes and Immunity · doi:10.1038/s41435-017-0006-8 · Cited by 20 · see citing works
“studies [4, 45, 46], DRB1*15:01~DQB1*06:02 confers very high disease risk in this population (OR= 3.”
Multiple sclerosis in Gypsies from southern Spain: prevalence, mitochondrial DNA haplogroups and HLA class II association
Fernández, Ó., Fernández, V., Martinez-Cabrera, V., Mayorga, C., Alonso, A., León, A., Arnal, C., Hens, M. J., Luque, G., de Ramón, E., et al. (2008) · Tissue Antigens · doi:10.1111/j.1399-0039.2008.01016.x · Cited by 20 · see citing works
6.7-kbp deletion in LILRA3 (ILT6) gene is associated with later onset of the multiple sclerosis in a Polish population
Wiśniewski, A., Wagner, M., Nowak, I., Bilińska, M. M., Pokryszko‐Dragan, A., Jasek, M., & Kuśnierczyk, P. (2012) · Human Immunology · doi:10.1016/j.humimm.2012.12.006 · Cited by 19 · see citing works
Familial multiple sclerosis in Greece: Distinct clinical and imaging characteristics in comparison with the sporadic disease
Katsavos, S., Artemiadis, A., Davaki, P., Stamboulis, E., Kilindireas, K., & Anagnostouli, M. C. (2018) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2018.08.021 · Cited by 19 · see citing works
Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients
Menascu, S., Khavkin, Y., Zilkha‐Falb, R., Dolev, M., Magalashvili, D., Achiron, A., & Gurevich, M. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51244 · Cited by 19 · see citing works
Multiple sclerosis in Colombia and other Latin American Countries
Toro, J., Cárdenas‐Robledo, S., Martínez, C., Urrutia, J., & Díaz, C. (2012) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2012.09.001 · Cited by 19 · see citing works
“(2010) did not find an association between MS frequency and HLA-DRB1n1501, which is the allele most consistently associated with MS worldwide (Schmidt et al., 2007; Hafler et al., 2007; Esposito et al., 2010), including Latin American countries such as Mexico (Al aez et al.”
Background
Interleukin 2 Receptor α Gene Polymorphism and Risk of Multiple Sclerosis: A Meta-Analysis
Wang, L., Zhang, D.-M., Xu, Y.-M., & Sun, S.-L. (2011) · Journal of International Medical Research · doi:10.1177/147323001103900505 · Cited by 19 · see citing works
Genetic factors and multiple sclerosis in the Moroccan population: A role for HLA class II
Ouadghiri, S., Taoussi, K. E. A., Brick, C., Benhaddou, E. H. A., Benseffaj, N., Benomar, A., Yahyaoui, M., & Essakalli, M. (2013) · Pathologie Biologie · doi:10.1016/j.patbio.2013.05.002 · Cited by 18 · see citing works
The polymorphisms of human leukocyte antigen loci may contribute to the susceptibility and severity of severe aplastic anemia in Chinese patients
Wang, M., Nie, N., Feng, S., Shi, J., Ge, M., Li, X., Shao, Y., Huang, J., & Zheng, Y. (2014) · Human Immunology · doi:10.1016/j.humimm.2014.06.011 · Cited by 18 · see citing works
Sex-Specific Environmental Impacts on Initiation and Progression of Multiple Sclerosis
Leffler, J., Trend, S., Gorman, S., & Hart, P. H. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.835162 · Cited by 18 · see citing works
“There are several risk factors for MS, including genetic polymorphisms, relating mainly to variants in HLA-DR, where HLA-DRB115:01 has the strongest link with increased risk of MS (13).”
Background
ALCAM — Novel multiple sclerosis locus interfering with HLA-DRB1*1501
Wagner, M., Wiśniewski, A., Bilińska, M. M., Pokryszko‐Dragan, A., Nowak, I., Kuśnierczyk, P., & Jasek, M. (2013) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2013.02.015 · Cited by 18 · see citing works
“This association on almost the same cohort of patients and controls was earlier detected in our laboratory and described by Wiśniewski et al. (2013). This result is in line with those obtained in most European populations (Schmidt et al.”
Result
Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis.
Atan, D., Heissigerova, J., Kuffová, L., Hogan, A. C., Kilmartin, D. J., Forrester, J. V., Bidwell, J. L., Dick, A. D., & Churchill, A. (2013) · Europe PMC (PubMed Central) · Cited by 17 · see citing works
Vitamin D receptor biochemical and genetic profiling and HLA-class II genotyping among Lebanese with multiple sclerosis — A pilot study
Yamout, B., Karaky, N., Mahfouz, R. A., Jaber, F., Estaitieh, N., Shammaa, D. M. R., Abbas, F., Hoteit, R. M., & Daher, R. T. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2016.02.008 · Cited by 17 · see citing works
“Furthermore, no interaction between DRB1*15 and DRB1*08 was observed in our study; a combination usually known to increase the susceptibility to MS (Schmidt et al., 2007).”
Multiple Sclerosis: Epidemiology, Genetics, Symptoms, and Unmet Needs
Moreno‐Torres, I., Muñoz, J. S., & García‐Merino, A. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788016070-00001 · Cited by 17 · see citing works
An impact of air pollution on moderate to severe relapses among multiple sclerosis patients
Elgabsi, M., Novack, L., Yarza, S., Elgabsi, M., Shtein, A., & Ifergane, G. (2021) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2021.103043 · Cited by 17 · see citing works
FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis
Kearns, P. K. A., Martin, S. J., Chang, J. C., Meijboom, R., York, E. N., Chen, Y., Weaver, C., Stenson, A., Hafezi, K., Thomson, S., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-058506 · Cited by 17 · see citing works
HLA-DRB1*15:01 and Epstein–Barr virus in a multiple sclerosis patient with psoriasis, nasopharyngeal and breast cancers. Lessons for possible hidden links for autoimmunity and cancer
Anagnostouli, M. C., Anagnostoulis, G., Katsavos, S., Panagiotou, M., Kararizou, E. G., & Davaki, P. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.02.003 · Cited by 17 · see citing works
“The various different conditions and subsequent treatments previously analyzed are summarized in Table 2, with comments on possible HLA and EBV correlations, based on the international literature [1,2,6–8,22–32].”
Method
Occupational Exposure and Risk of Central Nervous System Demyelination
Valery, P. C., Lucas, R. M., Williams, D. B., Pender, M. P., Chapman, C., Coulthard, A., Dear, K. B. G., Dwyer, T., Kilpatrick, T. J., McMichael, A. J., et al. (2013) · American Journal of Epidemiology · doi:10.1093/aje/kws361 · Cited by 17 · see citing works

Human Genome Epidemiology (HuGE) Review HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review
Schmidt, H., Williamson, D., & Ashley‐Koch, A. E. (2006)
Self-citation
Additive effect of the HLA-DR15 haplotype on susceptibility to multiple sclerosis
Rasmussen, H. B., Kelly, M. A., & Clausen, J. (2001) · Multiple Sclerosis Journal · doi:10.1177/135245850100700203 · Cited by 23 · see citing works
Evidence of Linkage with HLA-DR in DRB1*15-Negative Families with Multiple Sclerosis
Ligers, A., Dyment, D. A., Willer, C. J., Sadovnick, A. D., Ebers, G. C., RISCH, N. J., & Hillert, J. A. (2001) · The American Journal of Human Genetics · doi:10.1086/323480 · Cited by 76 · see citing works
Mapping Multiple Sclerosis Susceptibility to the HLA-DR Locus in African Americans
Oksenberg, J. R., Barcellos, L. F., Cree, B., Baranzini, S. E., Bugawan, T. L., Khan, O. A., Lincoln, R., Swerdlin, A., Mignot, E. J.-M., Lin, L., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/380997 · Cited by 334 · see citing works
Familial multiple sclerosis in a Brazilian sample: Is HLA-DR15 involved in susceptibility to the disease?
Bernardes, M. D. S., Paiva, C. L. A., Paradela, E. R., Alvarenga, M. P., Pereira, F. F., Vasconcelos, C. C. F., & Alvarenga, R. M. P. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.02.004 · Cited by 9 · see citing works

Authors: Schmidt, H., Williamson, D., & Ashley-Koch, A.
Affiliations: Accelerated Cure Project for Multiple Sclerosis (US)
Centers for Disease Control and Prevention (US)
ORCID: Schmidt, Hollie
Williamson, Dhelia
Venue: American Journal of Epidemiology
Publisher: Oxford University Press (OUP)
Published: 2007-02-28
Volume: 165
Issue: 10
Pages: 1097-1109
ISSN: 0002-9262 (ISSN-L)
1476-6256
DOI: 10.1093/aje/kwk118
OpenAlex: W2146798707
Cited by: 212
References: 146
Citations by year: 2026: 10 · 2025: 9 · 2024: 10 · 2023: 5 · 2022: 12 · 2021: 8 · 2020: 14 · 2019: 10 · 2018: 16 · 2017: 13 · 2016: 9 · 2015: 14 · 2014: 7 · 2013: 15 · 2012: 13
FWCI: 0.96
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Epidemiology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: multiple sclerosis, HLA-DRB1*1501, HLA-DQA1*0102, HLA-DQB1*0602, genetic susceptibility, HLA complex, allele frequency, case-control study, family-based association study, study design bias
MeSH terms: Alleles, Multigene Family, Haplotypes, HLA-D Antigens, Humans, Multiple Sclerosis

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HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review

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