HLA-DR4

The serological identification of DR4 is good. The serology of DRB1*04:17 to *04:60

is unknown.

DR4 is associated with extraarticular{{cite journal | author = Roudier J | title = HLA-DRB1 genes and extraarticular rheumatoid arthritis | journal = Arthritis Research & Therapy | volume = 8 | issue = 1 | pages = 103 | year = 2006 | pmid = 16542468 | doi = 10.1186/ar1886 | pmc = 1526581 | doi-access = free }} rheumatoid arthritis,{{cite journal | author = Winchester R | title = Genetic aspects of rheumatoid arthritis | journal = Springer Semin Immunopathol | volume = 4 | issue = 2 | pages = 89–102 | year = 1981 | pmid = 6459655 | doi = 10.1007/BF01857089| s2cid = 21303372 }} hydralazine-induced female systemic lupus erythematosus,{{cite journal |vauthors=Batchelor J, Welsh K, Tinoco R, Dollery C, Hughes G, Bernstein R, Ryan P, Naish P, Aber G, Bing R, Russell G | title = Hydralazine-induced systemic lupus erythematosus: influence of HLA-DR and sex on susceptibility | journal = Lancet | volume = 1 | issue = 8178 | pages = 1107–9 | year = 1980 | pmid = 6103441 | doi = 10.1016/S0140-6736(80)91554-8| s2cid = 27312391 }} pemphigoid gestationis,{{cite journal |vauthors=Shornick J, Jenkins R, Artlett C, Briggs D, Welsh K, Kelly S, Garvey M, Black M | title = Class II MHC typing in pemphigoid gestationis | journal = Clinical and Experimental Dermatology | volume = 20 | issue = 2 | pages = 123–6 | year = 1995 | pmid = 8565245 | doi = 10.1111/j.1365-2230.1995.tb02668.x| s2cid = 10047304 }} pemphigus foliaceus,{{cite journal | doi = 10.1111/j.1399-0039.1981.tb00689.x |vauthors=Matsuyama M, Hashimoto K, Yamasaki Y, Shirakura R, Higuchi R, Miyajima T, Amemiya H | title = HLA-DR antigens in pemphigus among Japanese | journal = Tissue Antigens | volume = 17 | issue = 2 | pages = 238–9 | year = 1981 | pmid = 7233418|s2cid=40684479 }} obstructive hypertrophic cardiomyopathy,{{cite journal |vauthors=Sakurami T, Ueno Y, Iwaki Y, Park M, Terasaki P, Saji H | title = HLA-DR specificities among Japanese with several autoimmune diseases | journal = Tissue Antigens | volume = 19 | issue = 2 | pages = 129–33 | year = 1982 | pmid = 6954729 | doi = 10.1111/j.1399-0039.1982.tb01428.x}} IgA nephropathy,{{cite journal |vauthors=Kashiwabara H, Shishido H, Tomura S, Tuchida H, Miyajima T | title = Strong association between IgA nephropathy and HLA-DR4 antigen | journal = Kidney Int | volume = 22 | issue = 4 | pages = 377–82 | year = 1982 | pmid = 6217371 | doi = 10.1038/ki.1982.185| doi-access = free }} 'shared syndrome'-systemic sclerosis/rheumatoid arthritis{{cite journal |vauthors=Szücs G, Szekanecz Z, Zilahi E, etal | title = Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity | journal = Rheumatology | volume = 46 | issue = 6 | pages = 989–93 | year = 2007 | pmid = 17384178 | doi = 10.1093/rheumatology/kem021| doi-access = free | hdl = 2437/89145 | hdl-access = free }} and polymyalgia rheumatica.Page 255 in: {{cite book |author1=Elizabeth D Agabegi |author2=Agabegi, Steven S. |title=Step-Up to Medicine (Step-Up Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year=2008 |isbn=978-0-7817-7153-5 |url-access=registration |url=https://archive.org/details/stepuptomedicine0000agab }}

DRB1*04 is associated with increased risk for alopecia areata.{{cite journal |vauthors=Entz P, Blaumeiser B, Betz RC, etal | title = Investigation of the HLA-DRB1 locus in alopecia areata | journal = European Journal of Dermatology | volume = 16 | issue = 4 | pages = 363–7 | year = 2006 | pmid = 16935791 }}

DRB1*04:01 is associated with multiple sclerosis,{{cite journal |vauthors=Laroni A, Calabrese M, Perini P, Albergoni M, Ranzato F, Tiberio M, Battistin L, Gallo P | title = Multiple sclerosis and autoimmune diseases : Epidemiology and HLA-DR association in North-east Italy | journal = J Neurol | volume = 253 | issue = 5 | pages = 636–9 | year = 2006 | pmid = 16502215 | doi = 10.1007/s00415-006-0084-4| s2cid = 35854155 }} rheumatoid arthritis,{{cite journal |vauthors=Angelini G, Morozzi G, Delfino L, Pera C, Falco M, Marcolongo R, Giannelli S, Ratti G, Ricci S, Fanetti G | title = Analysis of HLA DP, DQ, and DR alleles in adult Italian rheumatoid arthritis patients | journal = Hum Immunol | volume = 34 | issue = 2 | pages = 135–41 | year = 1992 | pmid = 1429034 | doi = 10.1016/0198-8859(92)90039-P}} type 1 diabetes,{{cite journal |vauthors=Fernandez-Viña M, Ramirez L, Raskin P, Stastny P | title = Genes for insulin-dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) of African-Americans | journal = Tissue Antigens | volume = 41 | issue = 2 | pages = 57–64 | year = 1993 | pmid = 8475491 | doi = 10.1111/j.1399-0039.1993.tb01980.x}}{{cite journal |vauthors=Undlien D, Friede T, Rammensee H, Joner G, Dahl-Jørgensen K, Søvik O, Akselsen H, Knutsen I, Rønningen K, Thorsby E | title = HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection | journal = Diabetes | volume = 46 | issue = 1 | pages = 143–9 | year = 1997 | pmid = 8971095 | doi = 10.2337/diabetes.46.1.143}} lyme disease induced arthritis.{{cite journal |vauthors=Gross D, Forsthuber T, Tary-Lehmann M, Etling C, Ito K, Nagy Z, Field J, Steere A, Huber B | title = Identification of LFA-1 as a candidate autoantigen in treatment-resistant Lyme arthritis | journal = Science | volume = 281 | issue = 5377 | pages = 703–6 | year = 1998 | pmid = 9685265 | doi = 10.1126/science.281.5377.703| bibcode = 1998Sci...281..703G }}

HLA-DRB1*04:01 gene variant is found three times more often in asymptomatic carriers of SARS-CoV-2 than in patients with symptoms of COVID-19. It is known that the prevalence of the HLA-DRB1*04:01 variant directly correlates with the latitude and longitude of the population. This variant of the gene is more common in northern and western Europe, which means that people of European descent are more likely to be asymptomatic carriers that can transmit the disease to more susceptible populations.{{cite journal

| vauthors=Bourke SC, Lie Benedicte A, Reiff G, Natu S, Darlay R, Burn J, Echevarria C

| title = The influence of HLA genotype on the severity of COVID-19 infection

| journal = HLA

| pages = 14–22| year = 2021 | volume = 98

| issue = 1

| pmid = 33896121 | doi = 10.1111/tan.14284

| pmc = 8251294

| doi-access = free}}

DRB1*04:02: drug-triggered{{cite journal |vauthors=Matzner Y, Erlich H, Brautbar C, Sanilevitch A, Landau M, Brenner S, Friedmann A | title = Identical HLA class II alleles predispose to drug-triggered and idiopathic pemphigus vulgaris | journal = Acta Derm Venereol | volume = 75 | issue = 1 | pages = 12–4 | year = 1995 | doi = 10.2340/00015555751214 | pmid = 7747528| doi-access = free }}/idiopathic pemphigus vulgaris,{{cite journal |vauthors=Sáenz-Cantele AM, Fernández-Mestre M, Montagnani S, Calebotta A, Balbas O, Layrisse Z | title = HLA-DRB1*0402 haplotypes without DQB1*0302 in Venezuelan patients with pemphigus vulgaris | journal = Tissue Antigens | volume = 69 | issue = 4 | pages = 318–325 | year = 2007 | pmid = 17389015 | doi = 10.1111/j.1399-0039.2007.00826.x}}{{cite journal |vauthors=Lee E, Lendas K, Chow S, Pirani Y, Gordon D, Dionisio R, Nguyen D, Spizuoco A, Fotino M, Zhang Y, Sinha A | title = Disease relevant HLA class II alleles isolated by genotypic, haplotypic, and sequence analysis in North American Caucasians with pemphigus vulgaris | journal = Hum Immunol | volume = 67 | issue = 1–2 | pages = 125–39 | year = 2006| pmid = 16698434 | doi = 10.1016/j.humimm.2005.09.003}} type 1 diabetes, SLE associated anti-cardiolipin and anti-β₂ glycoprotein I.{{cite journal |vauthors=Galeazzi M, Sebastiani G, Tincani A, Piette J, Allegri F, Morozzi G, Bellisai F, Scorza R, Ferrara G, Carcassi C, Font J, Passiu G, Smolen J, Papasteriades C, Houssiau F, Nebro A, Ramon Garrido E, Jedryka-Goral A, Marcolongo R | title = HLA class II alleles associations of anticardiolipin antibodies | journal = Lupus | volume = 9 | issue = 1 | pages = 47–55 | year = 2000 | pmid = 10715100 | doi=10.1177/096120330000900109 | s2cid = 208624924 }}

DRB1*04:03: polycystic ovary syndrome,{{cite journal |vauthors=Kaibe M, Takakuwa K, Murakawa H, Ishii K, Tamura M, Tanaka K | title = Studies on the human leukocyte antigens in patients with polycystic ovary syndrome in a Japanese population--possible susceptibility of HLA-A11 and -DRB1*0403 to patient population with polycystic ovary syndrome | journal = Am J Reprod Immunol | volume = 55 | issue = 4 | pages = 301–6 | year = 2006 | pmid = 16533342 | doi = 10.1111/j.1600-0897.2006.00369.x| s2cid = 34179090 }} SLE associated anti-cardiolipin and anti-β₂ glycoprotein I.{{cite journal |vauthors=Galeazzi M, Sebastiani G, Tincani A, Piette J, Allegri F, Morozzi G, Bellisai F, Scorza R, Ferrara G, Carcassi C, Font J, Passiu G, Smolen J, Papasteriades C, Houssiau F, Nebro A, Ramon Garrido E, Jedryka-Goral A, Marcolongo R | title = HLA class II alleles associations of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus | journal = Lupus | volume = 9 | issue = 1 | pages = 47–55 | year = 2000 | pmid = 10715100 | doi = 10.1177/096120330000900109| s2cid = 208624924 }}

DRB1*04:04: anti-citrullinated fibrinogen{{cite journal |vauthors=Auger I, Sebbag M, Vincent C, Balandraud N, Guis S, Nogueira L, Svensson B, Cantagrel A, Serre G, Roudier J | title = Influence of HLA-DR genes on the production of rheumatoid arthritis-specific autoantibodies to citrullinated fibrinogen | journal = Arthritis Rheum | volume = 52 | issue = 11 | pages = 3424–32 | year = 2005 | pmid = 16255019 | doi = 10.1002/art.21391}} in rheumatoid arthritis, autoimmune hepatitis.{{cite journal |vauthors=Vázquez-García M, Aláez C, Olivo A, Debaz H, Pérez-Luque E, Burguete A, Cano S, de la Rosa G, Bautista N, Hernández A, Bandera J, Torres L, Kershenobich D, Alvarez F, Gorodezky C | title = MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis | journal = J Hepatol | volume = 28 | issue = 6 | pages = 985–90 | year = 1998 | pmid = 9672174 | doi = 10.1016/S0168-8278(98)80347-4}}

DRB1*04:05: rheumatoid arthritis,{{cite journal |vauthors=Al-Swailem R, Al-Rayes H, Sobki S, Arfin M, Tariq M | title = HLA-DRB1 association in Saudi rheumatoid arthritis patients | journal = Rheumatol Int | volume = 26 | issue = 11 | pages = 1019–24 | year = 2006 | pmid = 16673133 | doi = 10.1007/s00296-006-0119-2| s2cid = 21900892 }} Autoimmune hepatitis,{{cite journal |vauthors=Ota M, Seki T, Kiyosawa K, Furuta S, Hino K, Kondo T, Fukushima H, Tsuji K, Inoko H | title = A possible association between basic amino acids of position 13 of DRB1 chains and autoimmune hepatitis | journal = Immunogenetics | volume = 36 | issue = 1 | pages = 49–55 | year = 1992 | pmid = 1350267 | doi = 10.1007/BF00209292| s2cid = 39851212 }} type 1 diabetes.

DRB1*04:06: caspase-8 autoantibodies silicosis-systemic sclerosis (SSc)-systemic lupus erythematosus (SLE).{{cite journal |vauthors=Ueki A, Isozaki Y, Kusaka M | title = Anti-caspase-8 autoantibody response in silicosis patients is associated with HLA-DRB1, DQB1 and DPB1 alleles | journal = J Occup Health | volume = 47 | issue = 1 | pages = 61–7 | year = 2005 | pmid = 15703453 | doi = 10.1539/joh.47.61| doi-access = free }}

DRB1*04:09: T. cruzi infection with cardiomyopathy.{{cite journal |vauthors=García Borrás S, Diez C, Cotorruelo C, etal | title = HLA class II DRB1 polymorphism in Argentinians undergoing chronic Trypanosoma cruzi infection | journal = Ann. Clin. Biochem. | volume = 43 | issue = Pt 3 | pages = 214–6 | year = 2006 | pmid = 16704757 | doi = 10.1258/000456306776865205| s2cid = 41178678 }}

DR4-DQ8 is a risk factor for papillary thyroid carcinoma,{{cite journal |vauthors=Porto T, Coelho I, Boavida J, etal | title = Association of HLA DQ4-DR8 haplotype with papillary thyroid carcinomas | journal = Clin. Endocrinol. | volume = 64 | issue = 2 | pages = 179–83 | year = 2006 | pmid = 16430717 | doi = 10.1111/j.1365-2265.2006.02445.x| s2cid = 22695710 }} juvenile diabetes, coeliac disease and rheumatoid arthritis.{{cite journal |vauthors=Singal D, Green D, Reid B, Gladman D, Buchanan W | title = HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA | journal = Ann Rheum Dis | volume = 51 | issue = 1 | pages = 23–8 | year = 1992 | pmid = 1371662 | doi = 10.1136/ard.51.1.23 | pmc = 1004612}}

DRB1*04:DQA1*03:03-DQB1*04:01 haplotype: type III autoimmune polyglandular syndrome,{{cite journal |vauthors=Hashimoto K, Maruyama H, Nishiyama M, Asaba K, Ikeda Y, Takao T, Iwasaki Y, Kumon Y, Suehiro T, Tanimoto N, Mizobuchi M, Nakamura T | title = Susceptibility alleles and haplotypes of human leukocyte antigen DRB1, DQA1, and DQB1 in autoimmune polyglandular syndrome type III in Japanese population | journal = Horm Res | volume = 64 | issue = 5 | pages = 253–60 | year = 2005 | pmid = 16254435 | doi = 10.1159/000089293| s2cid = 43559284 }} autoimmune hepatitis,{{cite journal |vauthors=Yoshizawa K, Ota M, Katsuyama Y, Ichijo T, Matsumoto A, Tanaka E, Kiyosawa K | title = Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis | journal = J Hepatol | volume = 42 | issue = 4 | pages = 578–84 | year = 2005 | pmid = 15763345 | doi = 10.1016/j.jhep.2004.12.019| url = https://soar-ir.repo.nii.ac.jp/?action=repository_action_common_download&item_id=4053&item_no=1&attribute_id=65&file_no=1 | hdl = 10091/219 | hdl-access = free }} autoimmune pancreatitis.{{cite journal |vauthors=Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, Nakayama K, Tokutake Y, Katsuyama Y, Saito S, Hasebe O, Kiyosawa K | title = HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population | journal = Gastroenterology | volume = 122 | issue = 5 | pages = 1264–9 | year = 2002 | pmid = 11984513 | doi = 10.1053/gast.2002.33022| doi-access = free }}

DRB1*04:DQA1*03-DQB1*03:02 haplotype: Type 1 diabetes{{cite journal |vauthors=Park Y, Tait B, Kawasaki E, Rowley M, Mackay I | title = Closer association of IA-2 humoral autoreactivity with HLA DR3/4 than DQB1*0201/*0302 in Korean T1D patients | journal = Ann N Y Acad Sci | volume = 1037 | pages = 104–9 | year = 2004| issue = 1 | pmid = 15699500 | doi = 10.1196/annals.1337.015| bibcode = 2004NYASA1037..104P | s2cid = 38178367 }}{{cite journal |vauthors=Hermann R, Turpeinen H, Laine A, Veijola R, Knip M, Simell O, Sipilä I, Akerblom H, Ilonen J | title = HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families | journal = Tissue Antigens | volume = 62 | issue = 2 | pages = 162–9 | year = 2003 | pmid = 12889996 | doi = 10.1034/j.1399-0039.2003.00071.x}} with DRB1*04:01, *04:05, *04:02 increasing risk when DQ8 is present.{{cite journal |vauthors=Thomson G, Valdes AM, Noble JA, etal | title = Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis | journal = Tissue Antigens | volume = 70 | issue = 2 | pages = 110–27 | year = 2007 | pmid = 17610416 | doi = 10.1111/j.1399-0039.2007.00867.x| doi-access = free }}

DRB1*01:01/*04:04 and *01:01/*04:01 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking.{{cite journal |vauthors=Mattey DL, Thomson W, Ollier WE, etal |title=Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study |journal=Arthritis Rheum. |volume=56 |issue=5 |pages=1408–16 |year=2007 |pmid=17469097 |doi=10.1002/art.22527}} these same genotypes are associated with rheumatoid vasculitis.{{cite journal |vauthors=Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA |title=Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis |journal=Arthritis Rheum. |volume=50 |issue=11 |pages=3476–84 |year=2004 |pmid=15529352 |doi=10.1002/art.20588}}

{{reflist}}

{{DR serotypes}}

{{DEFAULTSORT:Hla-Dr4}}

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