PMID- 33096882
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201030
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 9
IP  - 10
DP  - 2020 Oct 21
TI  - The HLA Variant rs6903608 Is Associated with Disease Onset and Relapse of 
      Immune-Mediated Thrombotic Thrombocytopenic Purpura in Caucasians.
LID - 10.3390/jcm9103379 [doi]
LID - 3379
AB  - Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, 
      life-threatening thrombotic microangiopathy caused by severe ADAMTS13 (a 
      disintegrin and metalloproteinase with thrombospondin motifs 13) deficiency, 
      recurring in 30-50% of patients. The common human leukocyte antigen (HLA) variant 
      rs6903608 was found to be associated with prevalent iTTP, but whether this 
      variant is associated with disease relapse is unknown. To estimate the impact of 
      rs6903608 on iTTP onset and relapse, we performed a case-control and cohort study 
      in 161 Italian patients with a first iTTP episode between 2002 and 2018, and in 
      456 Italian controls. Variation in rs6903608 was strongly associated with iTTP 
      onset (homozygotes odds ratio (OR) 4.68 (95% confidence interval (CI) 2.67 to 
      8.23); heterozygotes OR 1.64 (95%CI 0.95 to 2.83)), which occurred over three 
      years earlier for each extra risk allele (beta -3.34, 95%CI -6.69 to 0.02). Of 153 
      survivors (median follow-up 4.9 years (95%CI 3.7 to 6.1)), 44 (29%) relapsed. The 
      risk allele homozygotes had a 46% (95%CI 36 to 57%) absolute risk of relapse by 
      year 6, which was significantly higher than both heterozygotes (22% (95%CI 16 to 
      29%)) and reference allele homozygotes (30% (95%CI 23 to 39%)). In conclusion, 
      HLA variant rs6903608 is a risk factor for both iTTP onset and relapse. This 
      newly identified biomarker may help with recognizing patients at high risk of 
      relapse, who would benefit from close monitoring or intensified immunosuppressive 
      therapy.
FAU - Mancini, Ilaria
AU  - Mancini I
AUID- ORCID: 0000-0002-5059-5212
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, 20122 Milan, Italy.
FAU - Giacomini, Elisa
AU  - Giacomini E
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, 20122 Milan, Italy.
FAU - Pontiggia, Silvia
AU  - Pontiggia S
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, 20122 Milan, Italy.
FAU - Artoni, Andrea
AU  - Artoni A
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, 20122 Milan, Italy.
FAU - Ferrari, Barbara
AU  - Ferrari B
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, 20122 Milan, Italy.
FAU - Pappalardo, Emanuela
AU  - Pappalardo E
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, 20122 Milan, Italy.
FAU - Gualtierotti, Roberta
AU  - Gualtierotti R
AUID- ORCID: 0000-0001-6465-7624
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, 20122 Milan, Italy.
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, 20122 Milan, Italy.
FAU - Trisolini, Silvia Maria
AU  - Trisolini SM
AD  - Hematology, Department of Translational and Precision Medicine, "Sapienza" 
      University of Rome, 00161 Rome, Italy.
FAU - Capria, Saveria
AU  - Capria S
AD  - Hematology, Department of Translational and Precision Medicine, "Sapienza" 
      University of Rome, 00161 Rome, Italy.
FAU - Facchini, Luca
AU  - Facchini L
AD  - Hematology Unit, Azienda Unita Sanitaria Locale-IRCCS di Reggio Emilia, 42122 
      Reggio Emilia, Italy.
FAU - Codeluppi, Katia
AU  - Codeluppi K
AD  - Hematology Unit, Azienda Unita Sanitaria Locale-IRCCS di Reggio Emilia, 42122 
      Reggio Emilia, Italy.
FAU - Rinaldi, Erminia
AU  - Rinaldi E
AD  - Hematology Unit, A. Perrino Hospital, 72100 Brindisi, Italy.
FAU - Pastore, Domenico
AU  - Pastore D
AD  - Hematology Unit, A. Perrino Hospital, 72100 Brindisi, Italy.
FAU - Campus, Simona
AU  - Campus S
AD  - Pediatric Unit, Ospedale Microcitemico, 09121 Cagliari, Italy.
FAU - Caria, Cinzia
AU  - Caria C
AD  - Internal Medicine Unit, S.S. Trinita Hospital, 09121 Cagliari, Italy.
FAU - Caddori, Aldo
AU  - Caddori A
AD  - Internal Medicine Unit, S.S. Trinita Hospital, 09121 Cagliari, Italy.
FAU - Nicolosi, Daniela
AU  - Nicolosi D
AD  - Hematology Division, Department of Clinical and Molecular Biomedicine, University 
      of Catania, 95123 Catania, Italy.
FAU - Giuffrida, Gaetano
AU  - Giuffrida G
AD  - Hematology Division, Department of Clinical and Molecular Biomedicine, University 
      of Catania, 95123 Catania, Italy.
FAU - Agostini, Vanessa
AU  - Agostini V
AD  - U.O. Medicina Trasfusionale, IRCCS-Ospedale Policlinico San Martino, 16132 
      Genova, Italy.
FAU - Roncarati, Umberto
AU  - Roncarati U
AD  - U.O. Immunoematologia e Medicina Trasfusionale/Officina Trasfusionale, Cesena e 
      Forli, 47521 Cesena, Italy.
FAU - Mannarella, Clara
AU  - Mannarella C
AD  - Hematology Unit, Madonna delle Grazie Hospital, 75100 Matera, Italy.
FAU - Fragasso, Alberto
AU  - Fragasso A
AD  - Hematology Unit, Madonna delle Grazie Hospital, 75100 Matera, Italy.
FAU - Podda, Gian Marco
AU  - Podda GM
AUID- ORCID: 0000-0002-1791-8905
AD  - U.O. Medicina III, ASST Santi Paolo e Carlo, Dipartimento di Scienze della 
      Salute, Universita degli Studi di Milano, 20142 Milan, Italy.
FAU - Birocchi, Simone
AU  - Birocchi S
AD  - U.O. Medicina III, ASST Santi Paolo e Carlo, Dipartimento di Scienze della 
      Salute, Universita degli Studi di Milano, 20142 Milan, Italy.
FAU - Cerbone, Anna Maria
AU  - Cerbone AM
AD  - Department of Clinical Medicine and Surgery, AOU Federico II, 80131 Naples, 
      Italy.
FAU - Tufano, Antonella
AU  - Tufano A
AD  - Department of Clinical Medicine and Surgery, AOU Federico II, 80131 Naples, 
      Italy.
FAU - Menna, Giuseppe
AU  - Menna G
AD  - Department of Oncology, AORN Santobono-Pausilipon, 80122 Naples, Italy.
FAU - Pizzuti, Michele
AU  - Pizzuti M
AD  - Hematology Unit, AO San Carlo, 85100 Potenza, Italy.
FAU - Ronchi, Michela
AU  - Ronchi M
AD  - Internal Medicine Unit, Department of Medicine, Lugo Hospital, Lugo, 48022 
      Ravenna, Italy.
FAU - De Fanti, Alessandro
AU  - De Fanti A
AD  - Departmental Simple Unit of Pediatric Rheumatology, AUSL-IRCSS Reggio Emilia, 
      42123 Reggio Emilia, Italy.
FAU - Amarri, Sergio
AU  - Amarri S
AD  - Paediatrics Unit, AUSL-IRCSS Reggio Emilia, 42123 Reggio Emilia, Italy.
FAU - Defina, Marzia
AU  - Defina M
AD  - Department of Medical, Surgery and Neuroscience, Hematology Unit, Azienda 
      Ospedaliera Universitaria Senese, Universita degli Studi di Siena, 53100 Siena, 
      Italy.
FAU - Bocchia, Monica
AU  - Bocchia M
AUID- ORCID: 0000-0003-3538-3913
AD  - Department of Medical, Surgery and Neuroscience, Hematology Unit, Azienda 
      Ospedaliera Universitaria Senese, Universita degli Studi di Siena, 53100 Siena, 
      Italy.
FAU - Ceru, Silvia
AU  - Ceru S
AD  - Hematology Unit, Santa Chiara Hospital, 38122 Trento, Italy.
FAU - Gattillo, Salvatore
AU  - Gattillo S
AD  - Immuno-Hematology and Transfusion Medicine Unit, San Raffaele Hospital, 20132 
      Milan, Italy.
FAU - Rosendaal, Frits R
AU  - Rosendaal FR
AD  - Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA 
      Leiden, The Netherlands.
FAU - Peyvandi, Flora
AU  - Peyvandi F
AD  - Department of Pathophysiology and Transplantation, Universita degli Studi di 
      Milano, and Fondazione Luigi Villa, 20122 Milan, Italy.
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi 
      Hemophilia and Thrombosis Center, 20122 Milan, Italy.
LA  - eng
GR  - Bando Ricerca Corrente/Ministero della Salute/
PT  - Journal Article
DEP - 20201021
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC7589625
OTO - NOTNLM
OT  - ADAMTS13
OT  - HLA
OT  - autoimmune disease
OT  - genotyping
OT  - relapse
OT  - risk factor
OT  - thrombotic thrombocytopenic purpura
COIS- I.M. received honoraria for participating as a speaker at educational meetings 
      organized by Instrumentation Laboratory and Sanofi-Genzyme, outside the submitted 
      work. B.F. received honoraria for participating as a speaker at educational 
      meetings organized by Sanofi-Genzyme. R.G. reports personal fees from Biomarin 
      and Takeda, outside the submitted work. F.P. is a scientific advisory member of 
      Bioverativ, Roche, Sanofi-Genzyme, Sobi, outside the submitted work. V.A. 
      received honoraria for participating as a speaker at educational meetings 
      organized by CSL Behring and is a member of the Sanofi-Genzyme and Werfen-IL 
      scientific advisory boards, outside the submitted work. U.R. is a member of the 
      Sanofi-Genzyme scientific advisory board, outside the submitted work. M.B. 
      received honoraria for participating as a speaker at educational meetings 
      organized by Incyte and Janssen, outside the submitted work. The other authors do 
      not have any conflict of interests to disclose.
EDAT- 2020/10/25 06:00
MHDA- 2020/10/25 06:01
PMCR- 2020/10/21
CRDT- 2020/10/24 01:01
PHST- 2020/09/07 00:00 [received]
PHST- 2020/10/11 00:00 [revised]
PHST- 2020/10/15 00:00 [accepted]
PHST- 2020/10/24 01:01 [entrez]
PHST- 2020/10/25 06:00 [pubmed]
PHST- 2020/10/25 06:01 [medline]
PHST- 2020/10/21 00:00 [pmc-release]
AID - jcm9103379 [pii]
AID - jcm-09-03379 [pii]
AID - 10.3390/jcm9103379 [doi]
PST - epublish
SO  - J Clin Med. 2020 Oct 21;9(10):3379. doi: 10.3390/jcm9103379.