{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:16:14Z","timestamp":1791994574758,"version":"4.4.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Pemphigus vulgaris (PV) is an autoimmune bullous dermatosis with uneven geographic distribution and higher incidence in certain populations. In previous studies, a relatively high incidence of PV was reported in Bulgaria (0.47\/100,000\/year) comparable to that in other countries. The genetic background was considered responsible for the disease susceptibility, and multiple reports have proven PV to be an HLA-associated condition. The aim of our study was to analyze the role of genetic factors in the development of PV in Bulgaria. HLA genotyping was performed in 56 PV patients, ethnic Bulgarians whose diagnosis was confirmed based on clinical, histological, and immunofluorescent findings. The control group consisted of 204 healthy individuals from the Bulgarian population without evidence for HLA-associated autoimmune diseases. HLA-A,-B,-DRB1,-DQB1 analysis was performed by PCR-SSP. Our results revealed predisposing associations with DRB1*14, DRB1*04:02, and B*38, B*55, while allele DRB1*03:01 and the corresponding haplotypes were significantly decreased in the PV patients. The predisposing role of these alleles has been observed in other populations. All reported predisposing DRB1 alleles have the same amino acids at key positions of the beta chain of the HLA molecules, 26 (Phe), 67 (Leu or Ileu), 70 and 71 (hydrophobic AA: Gln, Arg, Asp, or Glu), and 86 (Val), which is important for the selective presentation of desmoglein 3 peptides. Additionally, specific alleles HLA-A*01 and DRB1*11 were identified with decreased frequencies in the patients\u2019 group, the last one being a common protective allele for autoimmune diseases in the Bulgarian population. The elucidation of the role of genetic factors for the development of pemphigus will help explain its higher incidence and clinical variability in certain populations.<\/jats:p>","DOI":"10.3389\/fimmu.2022.901386","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T04:28:43Z","timestamp":1659414523000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Association of specific HLA alleles and haplotypes with pemphigus vulgaris in the Bulgarian population"],"prefix":"10.3389","volume":"13","author":[{"given":"Kossara","family":"Drenovska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snejina","family":"Vassileva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Abu","family":"Shahid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissaveta","family":"Naumova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(95)80058-1","article-title":"Bullous skin diseases","volume":"7","author":"Nousari","year":"1995","journal-title":"Curr Opin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0303-6987.2006.00523.x","article-title":"How does acantholysis occur in pemphigus vulgaris: a critical review","volume":"33","author":"Lanza","year":"2006","journal-title":"J Cutan Pathol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111426","article-title":"Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies","volume":"74","author":"Stanley","year":"1984","journal-title":"J Clin Invest"},{"key":"B4","article-title":"Biochemical differentiation of types of pemphigus","volume":"46","author":"Eyre","year":"1989","journal-title":"Immunol Ser"},{"key":"B5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0140-6736(05)66829-8","article-title":"Pemphigus","volume":"366","author":"Bystryn","year":"2005","journal-title":"Lancet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"17026","DOI":"10.1038\/nrdp.2017.26","article-title":"Pemphigus","volume":"3","author":"Kasperkiewicz","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.390","article-title":"Desmoglein as a target in skin disease and beyond","volume":"132","author":"Amagai","year":"2012","journal-title":"J Invest Dermatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-018-8986-7","article-title":"Pemphigus group: overview, epidemiology, mortality, and comorbidities","volume":"66","author":"Kridin","year":"2018","journal-title":"Immunol Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1001\/archderm.129.1.69","article-title":"Pemphigus foliaceus in young women. an endemic focus in the sousse area of Tunisia","volume":"129","author":"Morini","year":"1993","journal-title":"Arch Dermatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12612836","article-title":"Comparative epidemiology of pemphigus in Tunisia and France: unusual incidence of pemphigus foliaceus in young Tunisian women","volume":"104","author":"Bastuji-Garin","year":"1995","journal-title":"J Invest Dermatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.10.009","article-title":"Geoepidemiologic considerations of auto-immune pemphigus","volume":"9","author":"Meyer","year":"2010","journal-title":"Autoimmun Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2021.100004","article-title":"Epidemiology of pemphigus","volume":"1","author":"Kridin","year":"2021","journal-title":"JID Innov"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02501.x","article-title":"Pemphigus: analysis of 1209 cases","volume":"44","author":"Chams-Davatchi","year":"2005","journal-title":"Int J Dermatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(74)90365-x","article-title":"Pemphigus vulgaris: incidence in jews of different ethnic groups, according to age, sex, and initial lesion","volume":"38","author":"Pisanti","year":"1974","journal-title":"Oral Surg Oral Med Oral Pathol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1980.01640330073017","article-title":"Pemphigus in Hartford county, Connecticut, from 1972 to 1977","volume":"116","author":"Simon","year":"1980","journal-title":"Arch Dermatol"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.2340\/0001555562491496","article-title":"Pemphigus: an epidemiological study of patients treated in Finnish hospitals between 1969 and 1978","volume":"62","author":"Hietanen","year":"1982","journal-title":"Acta Derm Venereol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1046\/j.1365-4362.1998.00428.x","article-title":"Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily","volume":"37","author":"Micali","year":"1998","journal-title":"Int J Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.2000.00864.x","article-title":"Epidemiology of pemphigus in Sofia, bulgaria. a 16-year retrospective study (1980-1995)","volume":"39","author":"Tsankov","year":"2000","journal-title":"Int J Dermatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-0960.1989.tb00405.x","article-title":"A five year retrospective study on pemphigus and pemphigoid","volume":"30","author":"Kyriakis","year":"1989","journal-title":"Australas J Dermatol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02421.x","article-title":"Some epidemiological features of pemphigus chronicus in south vojvodina: a 12-year retrospective study","volume":"44","author":"Golusin","year":"2005","journal-title":"Int J Dermatol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1111\/ddg.13081","article-title":"Incidence of autoimmune bullous diseases in Serbia: a 20-year retrospective study","volume":"14","author":"Milinkovi\u0107","year":"2016","journal-title":"J Dtsch Dermatol Ges"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2006.03010.x","article-title":"Epidemiology of pemphigus in Macedonia: a 15-year retrospective study (1990-2004)","volume":"46","author":"V'lckova-Laskoska","year":"2007","journal-title":"Int J Dermatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2011.07.003","article-title":"Autoimmune blistering diseases: incidence and treatment in Croatia","volume":"29","author":"Marinovic","year":"2011","journal-title":"Dermatol Clin"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2009.04345.x","article-title":"Pemphigus vulgaris is the most common autoimmune bullous disease in northwestern Romania","volume":"49","author":"Baican","year":"2010","journal-title":"Int J Dermatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2006.03044.x","article-title":"Epidemiologic survey of pemphigus vulgaris with oral manifestations in northern Greece: retrospective study of 129 patients","volume":"46","author":"Michailidou","year":"2007","journal-title":"Int J Dermatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4362.1995.tb01563.x","article-title":"Environmental factors influencing the biologic behavior of patterns of pemphigus vulgaris: epidemiologic approach","volume":"34","author":"Kyriakis","year":"1995","journal-title":"Int J Dermatol"},{"key":"B27","article-title":"Epidemiology of pemphigus in Turkey: One-year prospective study of 220 cases","volume":"25","author":"Yayli","year":"2017","journal-title":"Acta Dermatovenerol Croat"},{"key":"B28","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1046\/j.1468-3083.2002.00384.x","article-title":"Increased incidence of pemphigus vulgaris in southern europeans living in Germany compared with native germans","volume":"16","author":"Hahn-Ristic","year":"2002","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.13298","article-title":"Assessment of HLA-a, HLA-DR, and HLA-DQ alleles in patients with pemphigus vulgaris from eastern of Turkey","volume":"19","author":"Dere","year":"2020","journal-title":"J Cosmet Dermatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12418","article-title":"HLA DRB1* and DQB1* alleles are associated with disease severity in patients with pemphigus vulgaris","volume":"54","author":"Svecova","year":"2015","journal-title":"Int J Dermatol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.humimm.2003.09.019","article-title":"HLA-G is associated with pemphigus vulgaris in Jewish patients","volume":"65","author":"Gazit","year":"2004","journal-title":"Hum Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5580\/d7a","article-title":"Distribution of Jewish and non-Jewish haplotypes among pemphigus vulgaris patients worldwide","volume":"6","author":"Fridkis-Hareli","year":"2006","journal-title":"Internet J Dermatol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/iji.12052","article-title":"High susceptibility to pemphigus vulgaris due to HLA-DRB1*14:54 in the Slovak population","volume":"40","author":"P\u00e1rnick\u00e1","year":"2013","journal-title":"Int J Immunogenet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12796","article-title":"Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population","volume":"87","author":"Zivanovic","year":"2016","journal-title":"HLA."},{"key":"B35","article-title":"HLA-antigens in pemphigus","volume":"41","author":"Drenovska","year":"2002","journal-title":"Dermatol Venereol (Sofia)"},{"key":"B36","article-title":"Detection of immune-associated genetic markers of human disease","volume-title":"Detection of immune-associated genetic markers of human disease","author":"Mathews","year":"1984"},{"key":"B37","article-title":"HLA-class II polymorphism in Bulgarian patients with multiple sclerosis","volume":"1","author":"Naumova","year":"2000","journal-title":"Clin Applic Immunol Invest"},{"key":"B38","article-title":"HLA-class II associations with insulin dependent diabetes mellitus in the population of Bulgaria","volume":"28","author":"Naumova","year":"2001","journal-title":"Acta Med Bulgarica"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1999.00626.x","article-title":"Common human leukocyte antigen alleles in pemphigus vulgaris and pemphigus foliaceus Italian patients","volume":"113","author":"Lombardi","year":"1999","journal-title":"J Invest Dermatol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1996.tb02689.x","article-title":"HLA haplotypes and class II molecular alleles in sardinian and Italian patients with pemphigus vulgaris","volume":"48","author":"Carcassi","year":"1996","journal-title":"Tissue Antigens"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1998.tb03043.x","article-title":"Distribution of HLA class II alleles among Spanish patients with pemphigus vulgaris","volume":"52","author":"Gonz\u00e1lez-Escribano","year":"1998","journal-title":"Tissue Antigens"},{"key":"B42","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1006\/jaut.2000.0388","article-title":"HLA class II polymorphism contributes to specify desmoglein derived peptides in pemphigus vulgaris and pemphigus foliaceus","volume":"15","author":"Loiseau","year":"2000","journal-title":"J Autoimmun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/s0198-8859(03)00092-2","article-title":"Pemphigus vulgaris in Jewish patients is associated with HLA-a region genes: mapping by microsatellite markers","volume":"64","author":"Slomov","year":"2003","journal-title":"Hum Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2005.09.003","article-title":"Disease relevant HLA class II alleles isolated by genotypic, haplotypic, and sequence analysis in north American caucasians with pemphigus vulgaris","volume":"67","author":"Lee","year":"2006","journal-title":"Hum Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s0198-8859(97)00182-1","article-title":"Identical MHC markers in non-Jewish Iranian and ashkenazi Jewish patients with pemphigus vulgaris: possible common central Asian ancestral origin","volume":"57","author":"Mobini","year":"1997","journal-title":"Hum Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s10227-001-0157-z","article-title":"HLA haplotypes and class II molecular alleles in Argentinian patients with pemphigus vulgaris","volume":"6","author":"Glorio","year":"2002","journal-title":"J Cutan Med Surg"},{"key":"B47","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jaut.2016.04.007","article-title":"Differential HLA class I and class II associations in pemphigus foliaceus and pemphigus vulgaris patients from a prevalent southeastern Brazilian region","volume":"72","author":"Brochado","year":"2016","journal-title":"J Autoimmun"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13577","article-title":"Study of the association between human leukocyte antigens (HLA) and pemphigus vulgaris in Brazilian patients","volume":"56","author":"Gil","year":"2017","journal-title":"Int J Dermatol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1994.tb02390.x","article-title":"HLA-DQA1, -DQB1 and -DRB1 genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method","volume":"44","author":"Niizeki","year":"1994","journal-title":"Tissue Antigens"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1996.tb02690.x","article-title":"MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India","volume":"48","author":"Delgado","year":"1996","journal-title":"Tissue Antigens"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/s0198-8859(97)00203-6","article-title":"Pemphigus vulgaris autoantibody response is linked to HLA-DQB1*0503 in Pakistani patients","volume":"57","author":"Delgado","year":"1997","journal-title":"Hum Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.12071","article-title":"Association of human leukocyte antigen class I antigens in Iranian patients with pemphigus vulgaris","volume":"40","author":"Mortazavi","year":"2013","journal-title":"J Dermatol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-008-9244-x","article-title":"(DRB, DQA1 and DQB1) allele and haplotype frequencies in the patients with pemphigus vulgaris","volume":"29","author":"Shams","year":"2009","journal-title":"J Clin Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2005.03.006","article-title":"Genetic factors in pemphigus","volume":"24","author":"Tron","year":"2005","journal-title":"J Autoimmun"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28547","article-title":"T Cell control in autoimmune bullous skin disorders","volume":"116","author":"Hertl","year":"2006","journal-title":"J Clin Invest"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/437231","article-title":"A potential link between environmental triggers and autoimmunity","volume":"2014","author":"Vojdani","year":"2014","journal-title":"Autoimmune Dis"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92021","article-title":"Setting the target for pemphigus vulgaris therapy","volume":"2","author":"Ellebrecht","year":"2017","journal-title":"JCI Insight"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.901386\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T06:46:40Z","timestamp":1700894800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.901386\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2022.901386"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.901386","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]},"article-number":"901386"}}