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Article ; Online: Donor-specific HLA antibodies in predicting crossmatch outcome: Comparison of three different laboratory techniques.

Peräsaari, J P / Jaatinen, T / Merenmies, J

2017 Volume 46, Page(s) 23–28

Abstract: The virtual crossmatch, which is based on single antigen bead technology, is used in the prediction of crossmatch results. However, this assay differs in sensitivity and specificity from crossmatch methods. In our study, the results of physical ... ...

Abstract	The virtual crossmatch, which is based on single antigen bead technology, is used in the prediction of crossmatch results. However, this assay differs in sensitivity and specificity from crossmatch methods. In our study, the results of physical crossmatches, performed with three different methods, were assessed against virtual crossmatch results. The aim was to determine the potential cut-off values for donor specific antibodies (DSA) that would predict the crossmatch results obtained by different methods. The results of different crossmatch techniques were correlated with the virtual crossmatch. The receiver operating characteristic (ROC) analysis revealed the Flow cytometric crossmatch (FCXM) and Luminex crossmatch (LXM) to be the most accurate, with area under curve (AUC) values of 0.861 and 0.805, respectively. While we found that the virtual crossmatch correlated well with all the crossmatch results, FCXM produced the best results (83% of the DSA detected). LXM outperformed the other tests in terms of the accuracy in separating class II DSA.
MeSH term(s)	Blood Grouping and Crossmatching/methods ; Flow Cytometry ; Graft Rejection/diagnosis ; Graft Rejection/prevention & control ; HLA Antigens/immunology ; Histocompatibility Testing ; Humans ; Kidney Transplantation ; Microspheres ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Sensitivity and Specificity ; Tissue Donors ; Ureohydrolases/blood
Chemical Substances	HLA Antigens ; Ureohydrolases (EC 3.5.3.-) ; allantoicase (EC 3.5.3.4)
Language	English
Publishing date	2017-11-20
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1160846-8
ISSN	1878-5492 ; 0966-3274
ISSN (online)	1878-5492
ISSN	0966-3274
DOI	10.1016/j.trim.2017.11.002
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Zs.A 3784: Show issues

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Article ; Online: Shorter Cold Ischemia Time in Deceased Donor Kidney Transplantation Reduces the Incidence of Delayed Graft Function Especially Among Highly Sensitized Patients and Kidneys From Older Donors.

Lauronen, Jouni / Peräsaari, Juha P / Saarinen, Timo / Jaatinen, Taina / Lempinen, Marko / Helanterä, Ilkka

Transplantation proceedings

2019 Volume 52, Issue 1, Page(s) 42–49

Abstract: Background: Long cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome.: Materials and methods: ...

Abstract	Background: Long cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome. Materials and methods: Pretransplant histocompatibility tests were modernized at our laboratory in 2015, leading to significant decrease of time consumed for these enabling earlier surgery. The effects of this on kidney transplant CIT, DGF, and other clinical outcomes were studied. The study population consisted of 896 consecutive deceased donor kidney recipients, of which 442 patients received a transplant with the old crossmatch and 454 received a transplant with the new crossmatch. Results: CIT shortened from mean 20 hours 6 minutes to 15 hours 52 minutes (P < .001). The incidence of DGF was significantly reduced from 31% to 24% (P = .02). Reduction in the frequency of DGF was more pronounced among the highly sensitized patients (53% to 28%, P = .01) or in patients with pretransplant donor-specific antibodies (50% to 20%, P = .002) and among patients who received kidneys from donors older than 65 years (38% to 27%, P = .04). Conclusions: Process optimization that reduces CIT decreases occurrence of DGF, especially in highly sensitized patients and patients who receive kidneys from older donors.
MeSH term(s)	Adult ; Cold Ischemia/adverse effects ; Delayed Graft Function/etiology ; Female ; Graft Survival ; Humans ; Incidence ; Kidney Transplantation/adverse effects ; Kidney Transplantation/methods ; Male ; Middle Aged ; Risk Factors ; Time Factors
Language	English
Publishing date	2019-12-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2019.11.025
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Zs.A 835: Show issues

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Article ; Online: Human leucocyte antigens B08, DRB103 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children.

Ylinen, E / Salmela, L / Peräsaari, J / Jaatinen, T / Tenca, A / Vapalahti, O / Färkkilä, M / Jalanko, H / Kolho, K-L

Acta paediatrica (Oslo, Norway : 1992)

2017 Volume 106, Issue 2, Page(s) 322–326

Abstract: Aim: The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune ... ...

Abstract	Aim: The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. Methods: The study cohort comprised 19 paediatric patients (13 female) aged three years to 15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011, and followed up for four years and three months to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children, and the HLA antigen frequencies were compared with 19 807 records from the Finnish Bone Marrow Donor Registry. Results: All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B08;DRB103 or DRB113. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB104 was not found in the study cohort. Conclusion: Our study found that B08, DRB103 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients.
MeSH term(s)	Adolescent ; Biliary Tract Diseases/genetics ; Child ; Child, Preschool ; European Continental Ancestry Group/genetics ; Female ; Finland ; HLA-B8 Antigen/genetics ; HLA-DRB1 Chains/genetics ; Hepatitis, Autoimmune/genetics ; Humans ; Male
Chemical Substances	HLA-B8 Antigen ; HLA-DRB1 Chains
Language	English
Publishing date	2017-02
Publishing country	Norway
Document type	Journal Article
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.13641
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Um IV Zs.95: Show issues

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Article ; Online: Description of four new HLA alleles in the Finnish population: A03:283N, A68:167, C03:327, C03:361.

Polvi, A / Peräsaari, J / Linjama, T / Saarinen, T / Koskela, S / Voorter, C E M / Jaatinen, T

HLA

2017 Volume 91, Issue 1, Page(s) 61–62

Abstract: New HLA alleles found in the Finnish population: A*03:283N, A*68:167, C*03:327 and C*03:361. ...

Abstract	New HLA alleles found in the Finnish population: A03:283N, A68:167, C03:327 and C03:361.
MeSH term(s)	Alleles ; Female ; Finland ; HLA-A Antigens/genetics ; HLA-A3 Antigen/genetics ; HLA-C Antigens/genetics ; Humans ; Male
Chemical Substances	HLA-A Antigens ; HLA-A03 antigen ; HLA-A68 antigen ; HLA-A3 Antigen ; HLA-C Antigens ; HLA-C*03 antigen
Language	English
Publishing date	2017-10-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.13158
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Zs.A 661: Show issues

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Article ; Online: Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation.

Leukemia

2023 Volume 38, Issue 1, Page(s) 109–125

Abstract: Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 ... ...

Abstract	Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56
MeSH term(s)	Humans ; Tyrosine Kinase Inhibitors ; Hepatitis A Virus Cellular Receptor 2 ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Single-Cell Analysis
Chemical Substances	Tyrosine Kinase Inhibitors ; Hepatitis A Virus Cellular Receptor 2 ; Protein Kinase Inhibitors
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-023-02074-w
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Zs.A 2295: Show issues

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Article ; Online: Isolation of hematopoietic stem cells from human cord blood.

Jaatinen, Taina / Laine, Jarmo

Current protocols in stem cell biology

2007 Volume Chapter 2, Page(s) Unit 2A.2

Abstract: Enrichment of hematopoietic stem cells is based on the expression of certain surface antigens, such as CD34 and CD133, or on the lack of expression of lineage-specific antigens. Immunomagnetic positive selection of CD34(+) or CD133(+) cells is performed ... ...

Abstract	Enrichment of hematopoietic stem cells is based on the expression of certain surface antigens, such as CD34 and CD133, or on the lack of expression of lineage-specific antigens. Immunomagnetic positive selection of CD34(+) or CD133(+) cells is performed using paramagnetic microbeads conjugated to specific monoclonal antibodies (anti-human CD34 or anti-human CD133). In negative selection of lineage-negative (Lin(-)) cells, the unwanted cells are labeled with antibodies against known markers for mature hematopoietic cells (CD2, CD3, CD14, CD16, CD19, CD24, CD56, CD66b, and glycophorin A) and retained in the column. Unlabeled cells pass through the column and are collected as the Lin(-) cell fraction. Immunomagnetic cell sorting system MACS is a fast and gentle method to enrich hematopoietic stem cells. Viable and highly pure cells can be separated to be used in various downstream applications, such as flow cytometry and cell culture.
MeSH term(s)	AC133 Antigen ; Antigens, CD/metabolism ; Antigens, CD34/metabolism ; Cell Separation/methods ; Female ; Fetal Blood/cytology ; Fetal Blood/immunology ; Glycoproteins/metabolism ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/immunology ; Humans ; Immunomagnetic Separation ; Infant, Newborn ; Peptides/metabolism ; Pregnancy
Chemical Substances	AC133 Antigen ; Antigens, CD ; Antigens, CD34 ; Glycoproteins ; PROM1 protein, human ; Peptides
Language	English
Publishing date	2007-06
Publishing country	United States
Document type	Journal Article
ISSN	1938-8969
ISSN (online)	1938-8969
DOI	10.1002/9780470151808.sc02a02s1
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Article ; Online: Isolation of mononuclear cells from human cord blood by Ficoll-Paque density gradient.

Jaatinen, Taina / Laine, Jarmo

Current protocols in stem cell biology

2007 Volume Chapter 2, Page(s) Unit 2A.1

Abstract: When preparing stem cell specimens from cord blood, pre-enrichment of mononuclear cells is highly recommended to improve the recovery of rare stem cells. Mononuclear cells are easily isolated by density gradient centrifugation. In Ficoll-Paque density ... ...

Abstract	When preparing stem cell specimens from cord blood, pre-enrichment of mononuclear cells is highly recommended to improve the recovery of rare stem cells. Mononuclear cells are easily isolated by density gradient centrifugation. In Ficoll-Paque density gradient centrifugation, anticoagulant-treated and diluted cord blood is layered on the Ficoll-Paque solution and centrifuged. During centrifugation, erythrocytes and granulocytes sediment to the bottom layer. Lower density lymphocytes, together with other slowly sedimenting cells such as platelets and monocytes, are retained at the interface between the plasma and Ficoll-Paque, where they can be collected and subjected to subsequent isolation of hematopoietic stem cells or to the culture of mesenchymal stem cells.
MeSH term(s)	Cell Separation/methods ; Centrifugation, Density Gradient ; Female ; Fetal Blood/cytology ; Ficoll ; Humans ; Infant, Newborn ; Leukocytes, Mononuclear/cytology ; Pregnancy ; Stem Cells/cytology
Chemical Substances	Ficoll (25702-74-3)
Language	English
Publishing date	2007-06
Publishing country	United States
Document type	Journal Article
ISSN	1938-8969
ISSN (online)	1938-8969
DOI	10.1002/9780470151808.sc02a01s1
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Article ; Online: Febuxostat, But Not Allopurinol, Markedly Raises the Plasma Concentrations of the Breast Cancer Resistance Protein Substrate Rosuvastatin.

Lehtisalo, Minna / Keskitalo, Jenni E / Tornio, Aleksi / Lapatto-Reiniluoto, Outi / Deng, Feng / Jaatinen, Taina / Viinamäki, Jenni / Neuvonen, Mikko / Backman, Janne T / Niemi, Mikko

Clinical and translational science

2020 Volume 13, Issue 6, Page(s) 1236–1243

Abstract: Xanthine oxidase inhibitors febuxostat and allopurinol are commonly used in the treatment of gout. Febuxostat inhibits the breast cancer resistance protein (BCRP) in vitro. Rosuvastatin is a BCRP substrate and genetic variability in BCRP markedly affects ...

Abstract	Xanthine oxidase inhibitors febuxostat and allopurinol are commonly used in the treatment of gout. Febuxostat inhibits the breast cancer resistance protein (BCRP) in vitro. Rosuvastatin is a BCRP substrate and genetic variability in BCRP markedly affects rosuvastatin pharmacokinetics. In this study, we investigated possible effects of febuxostat and allopurinol on rosuvastatin pharmacokinetics. In a randomized crossover study with 3 phases, 10 healthy volunteers ingested once daily placebo for 7 days, 300 mg allopurinol for 7 days, or placebo for 3 days, followed by 120 mg febuxostat for 4 days, and a single 10 mg dose of rosuvastatin on day 6. Febuxostat increased the peak plasma concentration and area under the plasma concentration-time curve of rosuvastatin 2.1-fold (90% confidence interval 1.8-2.6; P = 5 × 10
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; Administration, Oral ; Adult ; Allopurinol/administration & dosage ; Allopurinol/pharmacokinetics ; Area Under Curve ; Cross-Over Studies ; Drug Interactions ; Febuxostat/administration & dosage ; Febuxostat/pharmacokinetics ; Female ; Healthy Volunteers ; Humans ; Intestinal Mucosa/metabolism ; Intestine, Small/metabolism ; Male ; Neoplasm Proteins/metabolism ; Rosuvastatin Calcium/administration & dosage ; Rosuvastatin Calcium/pharmacokinetics ; Young Adult
Chemical Substances	ABCG2 protein, human ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Neoplasm Proteins ; Febuxostat (101V0R1N2E) ; Allopurinol (63CZ7GJN5I) ; Rosuvastatin Calcium (83MVU38M7Q)
Language	English
Publishing date	2020-05-26
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.12809
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Article ; Online: HLA antigen, allele and haplotype frequencies and their use in virtual panel reactive antigen calculations in the Finnish population.

Haimila, K / Peräsaari, J / Linjama, T / Koskela, S / Saarinenl, T / Lauronen, J / Auvinen, M-K / Jaatinen, T

Tissue antigens

2013 Volume 81, Issue 1, Page(s) 35–43

Abstract: The human leukocyte antigen (HLA) antigen, allele and haplotype frequencies of the Finnish population are quite unique because of a rather restricted and homogeneous gene pool. This has a strong influence on finding suitable donors for transplant ... ...

Abstract	The human leukocyte antigen (HLA) antigen, allele and haplotype frequencies of the Finnish population are quite unique because of a rather restricted and homogeneous gene pool. This has a strong influence on finding suitable donors for transplant patients; hence knowledge about the HLA frequencies of the patient population is essential. Here we report the HLA antigen frequencies for a large population sample and show high resolution HLA allele frequencies for 11 loci, including the rarely typed DPA1 and DQA1 loci. Furthermore, the most common Finnish high resolution haplotypes are presented for five HLA loci. The study shows that there are fewer HLA haplotypes in the Finnish population compared with mixed populations, and the common Finnish HLA haplotypes are more frequent. Using HLA antibody identification and panel reactive antibody calculations we show that a virtual population-specific panel, combined with single antigen testing, gives a more accurate and reliable estimate of the reactivity of the recipient serum against potential solid organ donors within the Finnish population. The results can be directly used to improve donor search for patients waiting for stem cell transplantation and to allocate highly immunised patients accurately to acceptable mismatch programs.
MeSH term(s)	Alleles ; European Continental Ancestry Group ; Finland ; Gene Frequency ; HLA Antigens/genetics ; Haplotypes ; Humans ; Tissue Donors
Chemical Substances	HLA Antigens
Language	English
Publishing date	2013-01
Publishing country	England
Document type	Journal Article
ZDB-ID	120440-3
ISSN	1399-0039 ; 0001-2815
ISSN (online)	1399-0039
ISSN	0001-2815
DOI	10.1111/tan.12036
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Article ; Online: Conflicting HLA assignment by three different typing methods due to the apparent loss of heterozygosity in the MHC region.

Linjama, T / Impola, U / Niittyvuopio, R / Kuittinen, O / Kaare, A / Rimpiläinen, J / Volin, L / Peräsaari, J / Jaatinen, T / Lauronen, J / Saarinen, T / Juvonen, E / Partanen, J / Koskela, S

HLA

2016 Volume 87, Issue 5, Page(s) 350–355

Abstract: Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for ... ...

Abstract	Loss of heterozygosity (LOH) has been reported to cause false human leukocyte antigen (HLA) homozygous typing results in pre-transplant patients suffering from haematological malignancies, who in fact are HLA heterozygous. This poses a challenge for histocompatibility testing, as a stem cell graft from a genuinely HLA homozygous donor to a mistyped patient may lead to acute life-threatening graft-vs-host disease. LOH in the HLA region on chromosome 6 is known to be quite common in solid tumours, helping malignant cells to escape T-cell surveillance, but the incidence in haematological malignancies is less well known and the estimates vary. Here we report LOH in the HLA region of five patients with haematological malignancy. We found considerable differences in sensitivity between the three different HLA typing methods used in our laboratory: SSP was clearly the most sensitive method for detecting the lost haplotype, followed by rSSO, while SBT was the least sensitive technique. A subsequent, retrospective genotyping of 65 HLA homozygous haematological patients by SSP method showed no mistyped LOH cases in our laboratory in the past 10 years. The frequency of HLA homozygosity was found to be similar between haematological patients and control groups. It is important for an HLA laboratory to be aware of the differences in various HLA typing techniques' sensitivity for detecting an under-represented haplotype between HLA typing techniques when genotyping patients with haematological diseases. It is advisable for HLA laboratories to have at least two different methods with different sensitivities in their repertoire to be able to retype samples when a false homozygous result is suspected.
MeSH term(s)	Adult ; Aged ; Case-Control Studies ; HLA Antigens/metabolism ; Haplotypes/genetics ; Histocompatibility Testing/methods ; Homozygote ; Humans ; Loss of Heterozygosity/genetics ; Major Histocompatibility Complex ; Middle Aged
Chemical Substances	HLA Antigens
Language	English
Publishing date	2016-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.12770
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