PMID- 29675021
OWN - NLM
STAT- MEDLINE
DCOM- 20190625
LR  - 20190625
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Anti-Thyroid Peroxidase Reactivity Is Heightened in Pemphigus Vulgaris and Is 
      Driven by Human Leukocyte Antigen Status and the Absence of Desmoglein 
      Reactivity.
PG  - 625
LID - 10.3389/fimmu.2018.00625 [doi]
LID - 625
AB  - Pemphigus vulgaris (PV) belongs to an autoimmune disease cluster that includes 
      autoimmune thyroid disease (AITD), suggesting common mechanisms driving 
      autoimmune susceptibility. Our group has shown that PV patients exhibit 
      significant reactivity to AITD-related anti-thyroid peroxidase (anti-TPO), and 
      anti-TPO antibodies affect signaling pathways in keratinocytes similar to 
      anti-desmoglein (Dsg) 3 antibodies. To further assess the relevance of anti-TPO 
      reactivity in PV, we analyzed anti-TPO levels in 280 PV and 167 healthy control 
      serum samples across a comprehensive set of variable and static parameters of 
      disease activity and etiopathogenesis. PV patients have significantly higher 
      activity rates (A.R.s) for anti-TPO than healthy controls, but levels do not 
      differ between phases of clinical activity and remission. Patients that carry 
      both the PV-associated human leukocyte antigen (HLA) alleles DRB1*0402 and 
      DQB1*0503, or DQB1*0503 alone show a low prevalence of anti-TPO (A.R. 9.5 and 
      4.8%, respectively), while patients that lack expression of these alleles or 
      carry DRB1*0402 alone have a much higher prevalence of anti-TPO (A.R. 23.1 and 
      15.8%, respectively), suggesting that the absence of DQB1*0503 may predispose 
      patients to the development of anti-TPO antibodies. Similarly, anti-Dsg1(-)/3(-) 
      patients have a higher anti-TPO A.R. (26.9%) than anti-Dsg1(-)/3(+) (18.8%), 
      anti-Dsg1(+)/3(-) (14.3%), and anti-Dsg1(+)/3(+) (3.9%) patients. Our data 
      suggest that anti-TPO reactivity in PV is driven by genetic markers that may be 
      in linkage disequilibrium with the established PV-susceptibility alleles and that 
      this association drives the selection of a combination of anti-Dsg and anti-TPO 
      antibodies, with anti-TPO filling the gap in active patients that do not carry 
      the established PV-associated autoantibodies and/or are lacking the established 
      PV-HLA-susceptibility alleles.
FAU - Seiffert-Sinha, Kristina
AU  - Seiffert-Sinha K
AD  - Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, 
      Buffalo, NY, United States.
FAU - Khan, Shahzaib
AU  - Khan S
AD  - Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, 
      Buffalo, NY, United States.
FAU - Attwood, Kristopher
AU  - Attwood K
AD  - Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, 
      Buffalo, NY, United States.
FAU - Gerlach, John A
AU  - Gerlach JA
AD  - Biomedical Laboratory Diagnostics Program, Tissue Typing Laboratory, Michigan 
      State University, East Lansing, MI, United States.
FAU - Sinha, Animesh A
AU  - Sinha AA
AD  - Department of Dermatology, Jacobs School of Medicine and Biomedical Sciences, 
      Buffalo, NY, United States.
LA  - eng
PT  - Journal Article
DEP - 20180405
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Autoantibodies)
RN  - 0 (Desmogleins)
RN  - 0 (Epitopes)
RN  - 0 (HLA Antigens)
RN  - EC 1.11.1.8 (Iodide Peroxidase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibody Affinity
MH  - Autoantibodies/metabolism
MH  - Autoimmunity
MH  - Desmogleins/immunology
MH  - Epitopes/*immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Iodide Peroxidase/*immunology
MH  - Keratinocytes/*physiology
MH  - Male
MH  - Middle Aged
MH  - Pemphigus/genetics/*immunology
MH  - Signal Transduction
PMC - PMC5896579
OTO - NOTNLM
OT  - anti-desmoglein antibody
OT  - anti-thyroglobulin antibody
OT  - anti-thyroid peroxidase antibody
OT  - human leukocyte antigen
OT  - pemphigus vulgaris
EDAT- 2018/04/21 06:00
MHDA- 2018/04/21 06:01
PMCR- 2018/01/01
CRDT- 2018/04/21 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/03/13 00:00 [accepted]
PHST- 2018/04/21 06:00 [entrez]
PHST- 2018/04/21 06:00 [pubmed]
PHST- 2018/04/21 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.00625 [doi]
PST - epublish
SO  - Front Immunol. 2018 Apr 5;9:625. doi: 10.3389/fimmu.2018.00625. eCollection 2018.