Dataset Information

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin.

ABSTRACT: IVIG is occasionally used for preventing and treating severe infections of patients who are to undergo transplantation. Administration of IVIG, which includes high-titer antibodies (Abs) against HLA class I and II, might have a substantial influence on the HLA Ab test results of these patients. However, this issue has remained unreported.

Methods

Anti-HLA Ab titers were determined in 4 types of IVIG preparations, fresh frozen plasma, and the sera of 11 patients with hematological diseases before and after IVIG administration.

Results

Although anti-HLA Abs were not detected in any of the fresh frozen plasma products, various anti-HLA class I and II Abs were detected in all 4 IVIG preparations. Six out of 11 patients who had received IVIG showed a low titer of anti-HLA class II Abs, which were not detected before IVIG administration. Conversely, no anti-HLA class I Abs were detected in any of the 11 patients. Furthermore, all 4 (100%) patients who were positive for anti-HLA class II Abs initially and were assessable became negative for anti-HLA Abs after the discontinuation of IVIG treatment (median, d 79; range, d 22-192).

Conclusions

IVIG preparations consist of high-titer anti-HLA class I and II Abs, but the latter can be transiently detected in the sera of patients who had received IVIG. When these patients are screened for the presence of donor-specific Abs, some may be incorrectly deemed positive for HLA class II Abs. Thus, caution is necessary when only donor-specific Abs specific to class II HLAs are detected in patients.

SUBMITTER: Takamatsu H

PROVIDER: S-EPMC8133174 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin.

Takamatsu Hiroyuki H Yamada Shinya S Tsuji Noriaki N Nakagawa Noriharu N Matsuura Erika E Kasada Atsuo A Sato Keijiro K Hosokawa Kohei K Iwaki Noriko N Arahata Masahisa M Tanaka Hidenori H Nakao Shinji S

Transplantation direct 20210518 6

IVIG is occasionally used for preventing and treating severe infections of patients who are to undergo transplantation. Administration of IVIG, which includes high-titer antibodies (Abs) against HLA class I and II, might have a substantial influence on the HLA Ab test results of these patients. However, this issue has remained unreported.<h4>Methods</h4>Anti-HLA Ab titers were determined in 4 types of IVIG preparations, fresh frozen plasma, and the sera of 11 patients with hematological diseases ...[more]

PMID: 34036167

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Project description:Class II human leukocyte antigens (HLA II) are proteins involved in the human immunological adaptive response by binding and exposing some pre-processed, non-self peptides in the extracellular domain in order to make them recognizable by the CD4+ T lymphocytes. However, the understanding of HLA-peptide binding interaction is a crucial step for designing a peptide-based vaccine because the high rate of polymorphisms in HLA class II molecules creates a big challenge, even though the HLA II proteins can be grouped into supertypes, where members of different class bind a similar pool of peptides. Hence, first we performed the supertype classification of 27 HLA II proteins using their binding affinities and structural-based linear motifs to create a stable group of supertypes. For this purpose, a well-known clustering method was used, and then, a consensus was built to find the stable groups and to show the functional and structural correlation of HLA II proteins. Thus, the overlap of the binding events was measured, confirming a large promiscuity within the HLA II-peptide interactions. Moreover, a very low rate of locus-specific binding events was observed for the HLA-DP genetic locus, suggesting a different binding selectivity of these proteins with respect to HLA-DR and HLA-DQ proteins. Secondly, a predictor based on a support vector machine (SVM) classifier was designed to recognize HLA II-binding peptides. The efficiency of prediction was estimated using precision, recall (sensitivity), specificity, accuracy, F-measure, and area under the ROC curve values of random subsampled dataset in comparison with other supervised classifiers. Also the leave-one-out cross-validation was performed to establish the efficiency of the predictor. The availability of HLA II-peptide interaction dataset, HLA II-binding motifs, high-quality amino acid indices, peptide dataset for SVM training, and MATLAB code of the predictor is available at http://sysbio.icm.edu.pl/HLA .

Project description:BackgroundAssociations between human leukocyte antigens (HLA) alleles and cervical cancer are largely representative of squamous cell carcinoma (SCC), the major histologic subtype. We evaluated the association between HLA class I (A, B, and C) and class II (DRB1 and DQB1) loci and risk of cervical adenocarcinoma (ADC), a less common but aggressive histologic subtype.MethodsWe pooled data from the Eastern and Western US Cervical Cancer studies, and evaluated the association between individual alleles and allele combinations and ADC (n = 630 ADC; n = 775 controls). Risk estimates were calculated for 11 a priori (based on known associations with cervical cancer regardless of histologic type) and 38 non a priori common alleles, as odds ratios (OR) and 95% confidence intervals (CI), adjusted for age and study. In exploratory analysis, we compared the risk associations between subgroups with HPV16 or HPV18 DNA in ADC tumor tissues in the Western US study cases and controls.ResultsThree of the a priori alleles were significantly associated with decreased risk of ADC [DRB1*13:01 (OR = 0.61; 95% CI: 0.41-0.93), DRB1*13:02 (OR = 0.49; 95% CI: 0.31-0.77), and DQB1*06:03 (OR = 0.64; 95% CI: 0.42-0.95)]; one was associated with increased risk [B*07:02 (OR = 1.39; 95% CI: 1.07-1.79)]. Among alleles not previously reported, DQB1*06:04 (OR = 0.46; 95% CI: 0.27-0.78) was associated with decreased risk of ADC and remained significant after correction for multiple comparisons, and C*07:02 (OR = 1.41; 95% CI: 1.09-1.81) was associated with increased risk. We did not observe a difference by histologic subtype. ADC was most strongly associated with increased risk with B*07:02/C*07:02 alleles (OR = 1.33; 95% CI: 1.01-1.76) and decreased risk with DRB1*13:02/DQB1*06:04 (OR = 0.41; 95% CI: 0.21-0.80).ConclusionRESULTS suggest that HLA allele associations with cervical ADC are similar to those for cervical SCC. An intriguing finding was the difference in risk associated with several alleles restricted to HPV16 or HPV18-related tumors, consistent with the hypothesis that HLA recognition is HPV type-specific.

Dataset Information

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin.

Methods

Results

Conclusions

Publications

Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin.

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