PMID- 33227174
OWN - NLM
STAT- MEDLINE
DCOM- 20210705
LR  - 20210705
IS  - 2059-2310 (Electronic)
IS  - 2059-2302 (Print)
IS  - 2059-2302 (Linking)
VI  - 97
IP  - 2
DP  - 2021 Feb
TI  - Low incidence of IgA isotype of HLA antibodies in alloantigen exposed 
      individuals.
PG  - 101-111
LID - 10.1111/tan.14146 [doi]
AB  - Human leukocyte antigen (HLA) antibodies are induced by pregnancy, transfusion, 
      or transplantation. Serum from transplant recipients is regularly screened for 
      IgG HLA antibodies because of their clinical relevance for transplant outcome. 
      While other isotypes of HLA antibodies, such as IgA may also contribute to the 
      alloimmune response, validated detection assays for IgA HLA antibody detection 
      are lacking. Therefore, we modified the commonly used luminex screening assay for 
      IgG HLA antibody detection (IgG-LMX) into an IgA HLA antibody screening assay 
      (IgA-LMX). Optimization and validation was performed with IgG, IgA1, and IgA2 
      isotype variants of HLA-specific human recombinant monoclonal antibodies (mAbs). 
      Reactivity patterns of IgA1 and IgA2 isotype HLA-specific mAbs in IgA-LMX were 
      identical to those of the IgG isotype. Cross-reactivity with IgG and IgM 
      antibodies and nonspecific binding to the beads were excluded. Further assay 
      validation showed the absence of IgA HLA antibodies in serum from individuals 
      without alloantigen exposure (n = 18). When the IgA-LMX assay was applied to sera 
      from 289 individuals with known alloantigen exposure through pregnancy (n = 91) 
      or kidney transplantation (n = 198), IgA HLA antibodies were detected in 3.5% of 
      individuals; eight patients on the kidney retransplant waitlist and two women 
      immunized through pregnancy. The majority (90%) of IgA HLA antibodies were 
      directed against HLA class II and were always present in conjunction with IgG HLA 
      antibodies. Results of this study show that this validated IgA-LMX method can 
      serve as a screening assay for IgA HLA antibodies and that the incidence of IgA 
      HLA antibodies in alloantigen exposed individuals is low.
CI  - (c) 2020 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons 
      Ltd.
FAU - Car, Helena
AU  - Car H
AUID- ORCID: 0000-0003-1636-0644
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Karahan, Gonca E
AU  - Karahan GE
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Dreyer, Geertje J
AU  - Dreyer GJ
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Brand-Schaaf, Simone H
AU  - Brand-Schaaf SH
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - de Vries, Aiko P J
AU  - de Vries APJ
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - van Kooten, Cees
AU  - van Kooten C
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Kramer, Cynthia S M
AU  - Kramer CSM
AUID- ORCID: 0000-0003-1350-2336
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Roelen, Dave L
AU  - Roelen DL
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Claas, Frans H J
AU  - Claas FHJ
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Heidt, Sebastiaan
AU  - Heidt S
AUID- ORCID: 0000-0002-6700-188X
AD  - Department of Immunology, Leiden University Medical Center, Leiden, The 
      Netherlands.
AD  - Leiden Transplant Center, Leiden University Medical Center, Leiden, The 
      Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20201202
PL  - England
TA  - HLA
JT  - HLA
JID - 101675570
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin A)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantibodies)
RN  - 0 (Isoantigens)
SB  - IM
MH  - Alleles
MH  - Antibody Specificity
MH  - Female
MH  - HLA Antigens
MH  - Humans
MH  - Immunoglobulin A
MH  - Immunoglobulin G
MH  - Incidence
MH  - *Isoantibodies
MH  - *Isoantigens
PMC - PMC7898292
OTO - NOTNLM
OT  - HLA antibody screening
OT  - IgA antibody
OT  - luminex
OT  - pregnancy
OT  - transplantation
COIS- The authors declare no potential conflict of interest.
EDAT- 2020/11/24 06:00
MHDA- 2021/07/06 06:00
PMCR- 2021/02/22
CRDT- 2020/11/23 17:11
PHST- 2020/07/22 00:00 [received]
PHST- 2020/09/30 00:00 [revised]
PHST- 2020/11/09 00:00 [accepted]
PHST- 2020/11/24 06:00 [pubmed]
PHST- 2021/07/06 06:00 [medline]
PHST- 2020/11/23 17:11 [entrez]
PHST- 2021/02/22 00:00 [pmc-release]
AID - TAN14146 [pii]
AID - 10.1111/tan.14146 [doi]
PST - ppublish
SO  - HLA. 2021 Feb;97(2):101-111. doi: 10.1111/tan.14146. Epub 2020 Dec 2.