Presence of strong association of the major histocompatibility complex (MHC) class I allele HLA-A*26:01 with idiopathic hypoparathyroidism
CONTEXT: The pathogenesis of isolated hypoparathyroidism, also referred to as idiopathic hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation.
OBJECTIVE: We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH.
PATIENTS AND CONTROLS: A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study.
RESULTS: There was a significant increase of HLA class I alleles HLA-A*26:01 [P < 1.71 × 10(-34); odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08-14.16] and HLA-B*08:01 (P < 8.19 × 10(-6); OR = 2.59; 95% CI = 1.63-4.04) in patients with IH compared to healthy controls. However, the association of A*26:01 was primary because B*08:01 was in linkage disequilibrium with A*26:01. Although the major histocompatibility complex (MHC) is very polymorphic, several alleles of HLA loci share key residues at anchor positions in the peptide binding pockets such that similar peptides may be presented by different MHC molecules encoded by the same locus. These allelic forms with similar anchoring amino acids have been clustered in supertypes. An analysis of HLA-A locus supertypes A01, A02, A03, and A04 revealed that supertype A01 was significantly increased (P < 9.18 × 10(-9); OR = 2.95) in IH compared to controls. However, this increase in the supertype A01 was contributed by A*26:01 because 68.7% of the A01 samples had A*26:01. Other alleles of the supertype did not show any significant differences.
CONCLUSION: The strong association of HLA-A*26:01 suggests an important role of MHC class I-mediated presentation of autoantigenic peptides to CD8(+) cytotoxic T cells in the pathogenesis of IH. These data provide evidence for the autoimmune etiology of IH akin to other autoimmune disorders like type 1 diabetes and rheumatoid arthritis.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2012 |
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Erschienen: |
2012 |
Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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Enthalten in: |
The Journal of clinical endocrinology and metabolism - 97(2012), 9 vom: 17. Sept., Seite E1820-4 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Goswami, Ravinder [VerfasserIn] |
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Links: |
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Themen: |
Amino Acids |
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Anmerkungen: |
Date Completed 26.11.2012 Date Revised 08.04.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1210/jc.2012-1328 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM218843771 |
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100 | 1 | |a Goswami, Ravinder |e verfasserin |4 aut | |
245 | 1 | 0 | |a Presence of strong association of the major histocompatibility complex (MHC) class I allele HLA-A*26:01 with idiopathic hypoparathyroidism |
264 | 1 | |c 2012 | |
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500 | |a Date Completed 26.11.2012 | ||
500 | |a Date Revised 08.04.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a CONTEXT: The pathogenesis of isolated hypoparathyroidism, also referred to as idiopathic hypoparathyroidism (IH), is not clear. There is a paucity of information related to the immunogenetic basis of the disease due to its rarity. A recurrent theme of several autoimmune disorders is aberrant antigen presentation | ||
520 | |a OBJECTIVE: We investigated for the association of alleles of the human leukocyte antigen (HLA) class I and II loci with IH | ||
520 | |a PATIENTS AND CONTROLS: A total of 134 patients with IH and 902 healthy controls from the same ethnic background participated in the study | ||
520 | |a RESULTS: There was a significant increase of HLA class I alleles HLA-A*26:01 [P < 1.71 × 10(-34); odds ratio (OR) = 9.29; 95% confidence interval (CI) = 6.08-14.16] and HLA-B*08:01 (P < 8.19 × 10(-6); OR = 2.59; 95% CI = 1.63-4.04) in patients with IH compared to healthy controls. However, the association of A*26:01 was primary because B*08:01 was in linkage disequilibrium with A*26:01. Although the major histocompatibility complex (MHC) is very polymorphic, several alleles of HLA loci share key residues at anchor positions in the peptide binding pockets such that similar peptides may be presented by different MHC molecules encoded by the same locus. These allelic forms with similar anchoring amino acids have been clustered in supertypes. An analysis of HLA-A locus supertypes A01, A02, A03, and A04 revealed that supertype A01 was significantly increased (P < 9.18 × 10(-9); OR = 2.95) in IH compared to controls. However, this increase in the supertype A01 was contributed by A*26:01 because 68.7% of the A01 samples had A*26:01. Other alleles of the supertype did not show any significant differences | ||
520 | |a CONCLUSION: The strong association of HLA-A*26:01 suggests an important role of MHC class I-mediated presentation of autoantigenic peptides to CD8(+) cytotoxic T cells in the pathogenesis of IH. These data provide evidence for the autoimmune etiology of IH akin to other autoimmune disorders like type 1 diabetes and rheumatoid arthritis | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Amino Acids |2 NLM | |
650 | 7 | |a HLA-A Antigens |2 NLM | |
650 | 7 | |a HLA-A*26:01 antigen |2 NLM | |
650 | 7 | |a HLA-B Antigens |2 NLM | |
650 | 7 | |a HLA-DRB1 Chains |2 NLM | |
650 | 7 | |a Peptides |2 NLM | |
700 | 1 | |a Singh, Archana |e verfasserin |4 aut | |
700 | 1 | |a Gupta, Nandita |e verfasserin |4 aut | |
700 | 0 | |a Indian Genome Variation Consortium |e verfasserin |4 aut | |
700 | 1 | |a Rani, Rajni |e verfasserin |4 aut | |
700 | 1 | |a Brahmachari, Samir K |e investigator |4 oth | |
700 | 1 | |a Majumder, Partha P |e investigator |4 oth | |
700 | 1 | |a Mukerji, Mitali |e investigator |4 oth | |
700 | 1 | |a Habib, Saman |e investigator |4 oth | |
700 | 1 | |a Dash, Debasis |e investigator |4 oth | |
700 | 1 | |a Ray, Kunal |e investigator |4 oth | |
700 | 1 | |a Bahl, Samira |e investigator |4 oth | |
700 | 1 | |a Singh, Lalji |e investigator |4 oth | |
700 | 1 | |a Sharma, Abhay |e investigator |4 oth | |
700 | 1 | |a Roychoudhury, Susanta |e investigator |4 oth | |
700 | 1 | |a Chandak, G R |e investigator |4 oth | |
700 | 1 | |a Thangaraj, K |e investigator |4 oth | |
700 | 1 | |a Parmar, D |e investigator |4 oth | |
700 | 1 | |a Sengupta, Shantanu |e investigator |4 oth | |
700 | 1 | |a Bharadwaj, Dwaipayan |e investigator |4 oth | |
700 | 1 | |a Rath, Srikanta K |e investigator |4 oth | |
700 | 1 | |a Singh, Jagmohan |e investigator |4 oth | |
700 | 1 | |a Jha, Ganga Nath |e investigator |4 oth | |
700 | 1 | |a Virdi, Komal |e investigator |4 oth | |
700 | 1 | |a Rao, V R |e investigator |4 oth | |
700 | 1 | |a Sinha, Swapnil |e investigator |4 oth | |
700 | 1 | |a Singh, Ashok |e investigator |4 oth | |
700 | 1 | |a Mitra, Amit K |e investigator |4 oth | |
700 | 1 | |a Mishra, Shrawan K |e investigator |4 oth | |
700 | 1 | |a Pasha, Qadar |e investigator |4 oth | |
700 | 1 | |a Sivasubbu, Sridhar |e investigator |4 oth | |
700 | 1 | |a Pandey, Rajesh |e investigator |4 oth | |
700 | 1 | |a Baral, Aradhita |e investigator |4 oth | |
700 | 1 | |a Singh, Prashant K |e investigator |4 oth | |
700 | 1 | |a Sharma, Amitabh |e investigator |4 oth | |
700 | 1 | |a Kumar, Jitender |e investigator |4 oth | |
700 | 1 | |a Stobdan, Tsering |e investigator |4 oth | |
700 | 1 | |a Bhasin, Yasha |e investigator |4 oth | |
700 | 1 | |a Chauhan, Chitra |e investigator |4 oth | |
700 | 1 | |a Hussain, Ashiq |e investigator |4 oth | |
700 | 1 | |a Sundaramoorthy, Elyanambi |e investigator |4 oth | |
700 | 1 | |a Singh, S P |e investigator |4 oth | |
700 | 1 | |a Bandyopadhyay, Arun |e investigator |4 oth | |
700 | 1 | |a Dasgupta, Krishanu |e investigator |4 oth | |
700 | 1 | |a Reddy, A K |e investigator |4 oth | |
700 | 1 | |a Spurgeon, Charles J |e investigator |4 oth | |
700 | 1 | |a Idris, M Mohd |e investigator |4 oth | |
700 | 1 | |a Khanna, Vinay |e investigator |4 oth | |
700 | 1 | |a Dhawan, Alok |e investigator |4 oth | |
700 | 1 | |a Anand, Mohini |e investigator |4 oth | |
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700 | 1 | |a Bharti, R S |e investigator |4 oth | |
700 | 1 | |a Singh, Madhu |e investigator |4 oth | |
700 | 1 | |a Singh, Arvind P |e investigator |4 oth | |
700 | 1 | |a Khan, Anwar J |e investigator |4 oth | |
700 | 1 | |a Shah, Parag P |e investigator |4 oth | |
700 | 1 | |a Pant, A B |e investigator |4 oth | |
700 | 1 | |a Kaur, Rupinder |e investigator |4 oth | |
700 | 1 | |a Bisht, Kamlesh K |e investigator |4 oth | |
700 | 1 | |a Kumar, Ashok |e investigator |4 oth | |
700 | 1 | |a Rajamanickam, Victor |e investigator |4 oth | |
700 | 1 | |a Wilson, Eugene |e investigator |4 oth | |
700 | 1 | |a Thangadurai, Antony |e investigator |4 oth | |
700 | 1 | |a Jha, Pankaj K |e investigator |4 oth | |
700 | 1 | |a Maulik, Mahua |e investigator |4 oth | |
700 | 1 | |a Makhija, Neelam |e investigator |4 oth | |
700 | 1 | |a Rahim, Abdur |e investigator |4 oth | |
700 | 1 | |a Sharma, Sangeeta |e investigator |4 oth | |
700 | 1 | |a Chopra, Rupali |e investigator |4 oth | |
700 | 1 | |a Rana, Pooja |e investigator |4 oth | |
700 | 1 | |a Chidambaram, M |e investigator |4 oth | |
700 | 1 | |a Maitra, Arindam |e investigator |4 oth | |
700 | 1 | |a Chawla, Ruchi |e investigator |4 oth | |
700 | 1 | |a Soni, Suruchika |e investigator |4 oth | |
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700 | 1 | |a Khan, Mohd Nadeem |e investigator |4 oth | |
700 | 1 | |a Sutar, Sushanta Das |e investigator |4 oth | |
700 | 1 | |a Tuteja, Amit |e investigator |4 oth | |
700 | 1 | |a Narayansamy, K |e investigator |4 oth | |
700 | 1 | |a Shukla, Rachna |e investigator |4 oth | |
700 | 1 | |a Prakash, Swami |e investigator |4 oth | |
700 | 1 | |a Mahurkar, Swapna |e investigator |4 oth | |
700 | 1 | |a Mani, K Radha |e investigator |4 oth | |
700 | 1 | |a Hemavathi, J |e investigator |4 oth | |
700 | 1 | |a Bhaskar, Seema |e investigator |4 oth | |
700 | 1 | |a Khanna, Pankaj |e investigator |4 oth | |
700 | 1 | |a Ramalakshmi, G S |e investigator |4 oth | |
700 | 1 | |a Tripathi, Shalini Mani |e investigator |4 oth | |
700 | 1 | |a Thakur, Nikita |e investigator |4 oth | |
700 | 1 | |a Ghosh, Balaram |e investigator |4 oth | |
700 | 1 | |a Kukreti, Ritushree |e investigator |4 oth | |
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700 | 1 | |a Sudheer, G |e investigator |4 oth | |
700 | 1 | |a Mahajan, Anubha |e investigator |4 oth | |
700 | 1 | |a Chavali, Sreenivas |e investigator |4 oth | |
700 | 1 | |a Tabassum, Rubina |e investigator |4 oth | |
700 | 1 | |a Grover, Sandeep |e investigator |4 oth | |
700 | 1 | |a Gupta, Meenal |e investigator |4 oth | |
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700 | 1 | |a Nejatizadeh, Abdoulazim |e investigator |4 oth | |
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700 | 1 | |a Das, Swapan K |e investigator |4 oth | |
700 | 1 | |a Sharma, Shilpy |e investigator |4 oth | |
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