Stefan Schaub

Universitätsspital Basel, Bâle, Basel-City, Switzerland

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Publications (75)306.35 Total impact

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    ABSTRACT: This report describes a HLAMatchmaker-based antibody analysis of post-pregnancy sera with antibodies against child-specific HLA-DR epitopes. These sera were reactive in IgG-binding assays with single allele bead (SAB) panels on a Luminex platform. The antibody specificity analysis focused on DRB epitopes that have been recorded in the International HLA Epitope Registry ( as experimentally verified with informative antibodies but we also considered other eplets that predict potential epitopes. The SAB panel has in several instances two or more alleles corresponding the same serologically defined DR antigen and we selected six sera were with different reactivity patterns with DR1, DR4, DR13 and/or DR52 alleles. We demonstrate here how amino acid differences between these alleles can provide useful information in the determination of new epitope specificities of antibodies in these sera. Eight newly antibody-verified epitopes were identified including three that correspond to eplets paired with self-residue configurations. Epitope specificity information appears to be useful in the prediction of mismatch acceptability of non-SAB alleles within serological DR antigen groups.
    No preview · Article · Dec 2015 · Human immunology
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    ABSTRACT: Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes presented by recipient HLA class II (predicted indirectly recognizable HLA epitopes presented by HLA class II [PIRCHE-II]). In the present study, we evaluated the role of PIRCHE-II in child-specific HLA antibody formation during pregnancy. A total of 229 mother-child pairs were HLA typed. For all mismatched HLA class I molecules of the child, we subsequently predicted the number of HLA epitopes that could be presented by maternal HLA class II molecules. Child-specific antigens were classified as either immunogenic or nonimmunogenic HLA based on the presence of specific antibodies and correlated to PIRCHE-II numbers. Immunogenic HLA contained higher PIRCHE-II numbers than nonimmunogenic HLA. Moreover, the probability of antibody production during pregnancy increased with the number of PIRCHE-II. In conclusion, our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. Present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests the PIRCHE-II concept is universal.
    No preview · Article · Oct 2015 · American Journal of Transplantation

  • No preview · Article · Sep 2015
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    ABSTRACT: Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancer, mainly cutaneous squamous cell carcinoma (cSCC). Two genes (TMC6/EVER1 and TMC8/EVER2), mutated in epidermodysplasia verruciformis (EV) patients with an increased risk of cSCC development, contain numerous single-nucleotide polymorphisms (SNPs). To evaluate the effect of SNPs in both TMC/EVER genes on the different susceptibilities of RTRs to cSCC. We determined the occurrence of cSCC in 105 RTRs who were transplanted at least 7 years previously and investigated the frequency of 26 SNPs within both TMC/EVER genes in severely affected (n = 16) as well as in nonaffected RTRs (n = 25). Our data did not indicate a significant association between any SNP genotype and risk of cSCC development in RTRs. To clarify the correlation between SNPs in both TMC genes and cSCC development in RTRs, integrated investigations of large cohorts including both RTRs and immunocompetent individuals with consideration of cSCC status, SNP genotype and human papillomavirus status might be necessary. © 2015 S. Karger AG, Basel.
    No preview · Article · Jul 2015 · Dermatology
  • G Hönger · N Krähenbühl · S Dimeloe · M Stern · S Schaub · C Hess
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    ABSTRACT: How human leucocyte antigen (HLA) expression levels on human lymphocytes relate to clinically relevant in vitro cytotoxicity testing has not been defined. Here, cross-sectional (n = 14) and longitudinal (n = 6) semi-quantitative assessment of HLA expression on lymphocytes was performed. Complement-dependent cytotoxicity (CDC) and cellular allo-reactivity were assessed vis-à-vis target cells with defined levels of HLA expression. On CD4(+) and CD8(+) T-cells, and on B-cells, intra-individual HLA levels varied ≤1.5-fold, whereas inter-individual HLA expression varied 2.34-fold and 2.07-fold on CD4(+) and CD8(+) T-cells, respectively, and 2.90-fold on B-cells. Importantly, CDC crossmatch reactions induced by anti-HLA-A2 monoclonal antibody as well as patient sera solely containing HLA-A2 antibodies were significantly impacted by HLA-A2 expression levels on donor cells. Likewise, cytotoxicity of HLA-A2 reactive effector cells was induced proportionate to availability of HLA-A2. These data demonstrate that human HLA expression on lymphocytes from healthy blood donors is fairly stable intra-individually, yet varies significantly from person to person. Variability in HLA expression levels can impact functional cytotoxic reactions in vitro, including the widely used CDC crossmatch assay. Prospective studies are required to test the clinical relevance of this finding. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Apr 2015 · Tissue Antigens
  • P. Amico · S. Schaub
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    ABSTRACT: In this editorial, the authors question the use of modified single antigen bead assays for detection of IgG3+ or C1q‐binding donor‐specific antibodies in solid organ transplantation. See article by O'Leary et al on page 1003.
    No preview · Article · Mar 2015 · American Journal of Transplantation
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    ABSTRACT: IntroductionIn immunosuppressed hosts, rapid identification of microorganisms of bloodstream infections is crucial to ensuring effective antimicrobial therapy. Conventional culture requires up to 72 h from sample collection to pathogen identification.Methods We used the SepsiTyper Kit and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF; Microflex, Bruker) directly from positive blood culture (BacT/ALERT 3D, FN/FA vials; bioMérieux) in comparison to standard culture methodology (VITEK 2; bioMérieux) for species identification.ResultsA total of 62 consecutive positive blood cultures from immunosuppressed patients (solid organ or hematopoietic transplant recipients, or with febrile neutropenia) were analyzed. Culture yielded gram-negative bacteria (GNB) in 27/62 (43.5%) and gram-positive (GPB) in 35/62 (56.5%) vials. For GNB, the predominant species identified by MALDI-TOF and confirmed by VITEK were Escherichia coli (16/16 correctly identified) and Enterobacter cloacae (4/4), with a sensitivity and specificity of 92.6% and 100% respectively. For GPB, predominant species were Staphylococcus aureus (3/3), coagulase-negative staphylococci (12/24), and Enterococcus faecium (6/6) with a sensitivity of 100%, 60%, and 100%, respectively. The median time from blood collection to species identification was 27.4 h with MALDI-TOF identification and 46.6 h with conventional methodologyConclusions Using MALDI-TOF directly from positive blood cultures allowed a shorter time to identification with high sensitivity and specificity in immunosuppressed patients.This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2015 · Transplant Infectious Disease

  • No preview · Conference Paper · Jul 2014

  • No preview · Conference Paper · Jul 2014
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    ABSTRACT: Background: A modified single antigen bead (SAB) assay measuring C1q binding to human leukocyte antigen antibodies has recently been introduced. The aim of this study was to investigate the determinants of C1q binding on SAB. Methods: Sera from 73 sensitized patients were analyzed by the generic IgGpan as well as IgG subclass specific SAB assays and correlated with the standard and an anti-human globulin (AHG) enhanced C1q test. Results: Among 2,665 SABs with positive IgGpan results (mean fluorescence intensity [MFI]>500), strong complement-binding IgG1 and IgG3 subclasses accounted for a median of 99% (interquartile range, 76%-100%) of the total IgG amount. IgGpan MFI alone showed a very strong association with standard C1q positivity (r=0.72), which was superior to a model including all IgG subclass MFI (r=0.62). Combining all IgG subclass MFI and IgGpan MFI only marginally improved the prediction of standard C1q positivity compared with IgGpan MFI alone (Δr=0.02). IgGpan MFI greater than 14,154 predicted standard C1q positivity, with 92% sensitivity and 96% specificity. Notably, 1,840 (93%) of the 1,974 C1q-negative SABs contained human leukocyte antigen antibodies with strong complement-binding IgG1 and IgG3 subclasses. Anti-human globulin significantly enhanced the signal in the C1q assay, but the association of AHG C1q positivity with IgGpan MFI was less strong (r=0.51). Conclusion: C1q binding on SAB is strongly associated with IgGpan MFI. IgG subclass information only marginally improves prediction of C1q binding likely because complement-binding IgG1 and IgG3 subclasses dominate regarding frequency and relative amounts. A negative C1q assay result does not indicate the absence of strong complement-binding IgG subclasses.
    No preview · Article · Jun 2014 · Transplantation
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    ABSTRACT: Non-HLA antibodies against the angiotensin II type 1 receptor (AT1 R) and the C-terminal fragment of perlecan (i.e., LG3) are associated with the development of renal allograft rejection. It is currently unknown how humans develop anti-AT1 R or anti-LG3 antibodies. The aim of this study was to investigate whether pregnancy-as a model of sensitization to polymorphic proteins-induces anti-AT1 R and/or anti-LG3 antibodies. We included 104 samples from women obtained after physiologic full-term pregnancy and 80 samples from healthy nonsensitized controls (40 women and 40 men). Both anti-AT1 R and anti-LG3 antibody levels were lower in pregnancy samples than in controls (both P < 0.05). By multivariate analysis, male gender was an independent predictor for high anti-AT1 R antibody levels (OR 3.66, P = 0.04) and pregnancy was predictive for low anti-LG3 antibody levels (OR 6.53, P = 0.0001). There was no correlation of anti-AT1 R with anti-LG3 antibody levels, either in the pregnancy or in the control samples (r(2) ≤ 0.03, P ≥ 0.26). In conclusion, physiologic full-term pregnancy does not induce anti-AT1 R or anti-LG3 antibodies and may even lower their levels. Therefore, anti-AT1 R and anti-LG3 antibodies are likely not caused by allosensitization. The lack of correlation of anti-AT1 R with anti-LG3 antibodies suggests different mechanisms of generation, which remain to be elucidated.
    No preview · Article · Feb 2014 · Transplant International
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    ABSTRACT: The aim of this study was to evaluate risk factors and outcome of expanded-criteria donor (ECD) kidney transplants in patients with low immunological risk. We evaluated graft survival and graft function in 265 recipients with low immunological risk defined as the absence of pretransplant donor-specific HLA antibodies. A total of 112 (42%) kidneys derived from ECD and 153 (58%) from standard-criteria donors (SCDs). Overall, in a multivariate Cox regression, ECD status was the only significant risk factor for graft failure (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.37; p = 0.01). In the SCD group there was an increased risk for graft failure with increasing recipient age (HR 1.06 per year, CI 1.01-1.10; p = 0.02) and in the ECD group a trend for risk reduction for recipients treated with tacrolimus (Tac) (HR 0.46, CI 0.20‒1.06; p = 0.07). One, three and five-year graft survival of ECD kidneys was significantly better when recipients were treated with Tac (95%, 88% and 72%, respectively) than when they were treated without Tac (73%, 65% and 50%, respectively) (p = 0.008). At three years, ECD kidneys had a lower median estimated creatinine clearance (eCrCl) than SCD kidneys (37 vs 58 ml/min, p <0.001). Within the ECD group, recipients treated with Tac had a higher median eCrCl than those treated without Tac (41 ml/min vs 33 ml/min, p = 0.004). Graft function from one to three years was preserved in ECD recipients treated with Tac (median change 0.0 ml/min, p = 0.4) compared with those treated without Tac (median change -3.2 ml/min, p = 0.005). Tac-based immunosuppression seems to improve graft survival and to preserve graft function in ECD kidneys with low immunological risk.
    No preview · Article · Nov 2013 · Schweizerische medizinische Wochenschrift
  • Stefan Schaub · Patricia Hirt-Minkowski
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    ABSTRACT: To the Editor: Suthanthiran et al. (July 4 issue)(1) describe their use of a three-gene signature (interferon-inducible protein 10 [IP-10] messenger RNA [mRNA], 18S ribosomal RNA [rRNA], and CD3 epsilon mRNA) in urinary cells to diagnose acute T-cell-mediated rejection in renal-allograft recipients. The diagnostic characteristics were determined by comparing 43 urine samples with T-cell-mediated rejection of Banff grade IA or higher with 163 urine samples that did not show rejection. Twenty-nine samples that showed antibody-mediated rejection or borderline changes were not included in the analysis or assigned to the no rejection group (see the Supplementary Results section in the Supplementary Appendix ...
    No preview · Article · Nov 2013 · New England Journal of Medicine
  • Stefan Schaub · Gideon Hönger · Patrizia Amico
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    ABSTRACT: In the past years, our ability to detect HLA-antibodies has significantly improved allowing for a better assessment of the humoral immune response. The presence of donor-specific HLA-antibodies [DSA] both pre-transplant and de novo post-transplant is associated with the occurrence of antibody-mediated rejection [AMR] and inferior allograft survival (1,2). However, patients with DSA demonstrate variable clinical courses. Therefore, it is of major interest to better define the „pathogenicity” of individual DSA, which could help to guide diagnostic and therapeutic interventions. One possible approach is to explore the humoral immune response in more detail by measuring the IgG sublcasses and the IgA/IgM-factions of HLA-antibodies. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2013 · Transplant International
  • T Menter · M Mayr · S Schaub · M J Mihatsch · H H Hirsch · H Hopfer
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    ABSTRACT: Control of polyomavirus BK (BKV) is achieved by reducing immunosuppression allowing an effective BKV-specific T-cell response. The morphology of resolving BKV-associated nephropathy (PyVAN) has not been systematically investigated. Ninety-nine surveillance biopsies of 35 patients with BKV viremia treated exclusively by immunosuppression reduction were scored according to Banff criteria and grouped relative to BKV viremia as pre-, increasing, decreasing and post-BKV viremia. Thirty-four of 35 patients (97%) cleared BKV viremia after a median of 9 months posttransplantation. The tubulitis score, extent of tubules with intraepithelial lymphocytes, and interstitial inflammation significantly increased from the time of increasing to decreasing viremia. Tubulointerstitial inflammation, to a lower extent, persisted after clearance. The number of SV40+ tubules correlated with the BKV load in plasma, but SV40 immunohistochemistry was frequently negative (60%). During decreasing viremia, 31% of PyVAN cases were plasma cell-rich and 40% showed tubular HLA-DR expression. Compared to baseline 1 month posttransplantation, allograft function remained stable or improved in 29/35 patients (83%) after a median follow-up of 48 months. Within 1 year after clearance of BKV viremia, clinical rejection occurred in 2/35 patients (6%). Our data suggest that resolving PyVAN is typically characterized by a self-limiting acute interstitial nephritis, morphologically indistinguishable from interstitial rejection.
    No preview · Article · Jun 2013 · American Journal of Transplantation
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    ABSTRACT: One of the major tasks of human leukocyte antigen (HLA) laboratories is the pretransplant determination of unacceptable HLA antigen mismatches (UAM) in organ transplant recipients. HLA antigen specificities are determined against which the patient has circulating alloantibodies that are expected to harm the transplanted organ. Using the information on UAM, negative crossmatch (XM) prediction or 'virtual XM' is possible when a potential donor's complete HLA typing is available. Before the introduction of solid-phase antibody detection assays, UAM were determined using the complement-dependent cytotoxicity methodology. After the introduction of the single antigen bead technique, however, various UAM determination algorithms have emerged. In this report, six different laboratories worldwide present how they determine UAM in their collective of kidney transplant recipients in the pretransplant phase and proceed thereafter to transplantation.
    Full-text · Article · May 2013 · Tissue Antigens
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    ABSTRACT: Background: Kidneys from pediatric donors weighing <10 kg are preferably transplanted en bloc, while kidneys from donors weighing >15 kg can be safely transplanted as single kidneys. However, single kidney transplantation from donors weighing 10-14 kg is controversial and has not been well investigated. Methods: We analyzed the outcome of 15 recipients of single kidneys from donors weighing 10-14 kg (study group) with 40 recipients receiving an allograft from ideal deceased donors (control group). Results: After a follow-up of three yr, death-censored graft survival was 100% in both groups. The calculated creatinine clearance was lower in the study group at six months (53 vs. 71 mL/min; p = 0.01) and similar at 12 months (68 vs. 68 mL/min; p = 0.48), 24 months (81 vs. 70 mL/min; p = 0.58), and 36 months (74 vs. 69 mL/min; p = 0.59). Urinary albumin/creatinine ratios were comparable between the two groups up to two yr. At three yr, urinary albumin/creatinine ratios were higher in the study group than the control group (10.5 vs. 0.9 mg/mmol; p = 0.007). Surveillance biopsies at three and six months post-transplant revealed no evidence for focal segmental glomerulosclerosis in the study group. Conclusions: Transplantation of single pediatric kidneys from donors weighing 10-14 kg into adult recipients provides excellent intermediate-term outcomes. Low-grade albuminuria, three yr post-transplant, might indicate late-onset hyperfiltration injury.
    No preview · Article · Mar 2013 · Clinical Transplantation
  • G Hönger · I Fornaro · C Granado · J-M Tiercy · I Hösli · S Schaub
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    ABSTRACT: The aim of this study was to define the frequency and determinants of pregnancy-induced child-specific sensitization shortly after full-term delivery using sensitive single HLA-antigen beads (SAB) and high resolution HLA-typing of the mothers and their children (n = 301). A positive SAB result was defined by a background normalized ratio >1 or a mean fluorescence intensity (MFI) >300, >500 and >1000, respectively. The overall frequency of pregnancy-induced sensitization determined by SAB shortly after full-term delivery was between 45% (MFI > 1000 cut-off) and 76% (ratio cut-off). The rate of child-specific sensitization at the HLA-A/B/C/DRB1 loci was between 28% (MFI > 1000 cut-off) and 38% (ratio cut-off). The number of live birth was associated with a higher frequency of sensitization, which was driven by child-specific, but not third party HLA-antibodies. There was a clear hierarchy of sensitization among the investigated loci (B-locus: 31%; A-locus: 26%; DRB1-locus: 20%; C-locus: 15%; p < 0.0001). Some mismatched paternal HLA-antigens led to a significantly higher rate of sensitization than the average (e.g. HLA-A2, HLA-B49, HLA-B51, HLA-C*15). Furthermore, the mother's own HLA-phenotype-especially HLA-A/B homozygosity-was associated with a higher rate and broadness of sensitization. The number of mismatched HLA-A/B/C eplets strongly correlated with the rate of child-specific class I sensitization.
    No preview · Article · Jan 2013 · American Journal of Transplantation
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    ABSTRACT: Progressive interstitial fibrosis and tubular atrophy (IF/TA) is a leading cause of chronic allograft dysfunction. Increased extracellular matrix remodelling regulated by matrix metalloproteases (MMPs) and their inhibitors (TIMPs) has been implicated in the development of IF/TA. The aim of this study was to investigate whether urinary/serum MMPs/TIMPs correlate with subclinical IF/TA detected in surveillance biopsies within the first 6 months post-transplant. We measured eight different MMPs/TIMPs simultaneously in urine and serum samples from patients classified as normal histology (n = 15), IF/TA 1 (n = 15) and IF/TA 2-3 (n = 10). There was no difference in urinary MMPs/TIMPs among the three groups, and only 1/8 serum MMPs/TIMPs (i.e. MMP-1) was significantly elevated in biopsies with IF/TA 2-3 (p = 0.01). In addition, urinary/serum MMPs/TIMPs were not different between surveillance biopsies demonstrating an early development of IF/TA (i.e. delta IF/TA ≥ 1 compared to a previous biopsy obtained three months before; n = 11) and stable grade of IF/TA (i.e. delta IF/TA = 0; n = 20). Next, we investigated whether urinary/serum MMPs/TIMPs levels are elevated during acute subclinical tubulitis in surveillance biopsies obtained within the first 6 months post-transplant (n = 25). Compared to biopsies with normal histology, serum MMPs/TIMPs were not different; however, all urinary MMPs/TIMPs levels were numerically higher during subclinical tubulitis (MMP-1, MMP-7, TIMP-1 with p ≤ 0.04). We conclude that urinary/serum MMPs/TIMPs do hardly correlate with existing or early developing IF/TA in surveillance biopsies obtained within the first 6 months post-transplant. This could be explained by the dynamic process of extracellular matrix remodelling, which seems to be active during acute tubulo-interstitial injury/inflammation, but not in quiescent IF/TA.
    No preview · Article · Jan 2013 · Transplant Immunology
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    ABSTRACT: In this multicentre study, sera from 803 retransplant candidates, including 775 kidney transplant recipients, were analysed with regard to the presence and specificity of anti-HLA alloantibodies of the IgA isotype using a modified microsphere-based platform. Of the kidney recipients, nearly one-third (n = 237, 31%) had IgA alloantibodies. Mostly, these antibodies were found in sera that also harboured IgG alloantibodies that could be found in a total of 572 (74%) of patients. Interestingly, IgA anti-HLA antibodies were preferentially targeting HLA class I antigens in contrast to those of the IgG isotype, which targeted mostly both HLA class I and II antigens. Donor specificity of the IgA alloantibodies could be established for over half of the 237 patients with IgA alloantibodies (n = 124, 52%). A further 58 patients had specificities against HLA-C or HLA-DP, for which no information regarding donor typing was available. In summary, these data showed in a large cohort of retransplant candidates that IgA alloantibodies occur in about one-third of patients, about half of these antibodies being donor specific.
    No preview · Article · Dec 2012 · International Journal of Immunogenetics

Publication Stats

2k Citations
306.35 Total Impact Points


  • 2002-2015
    • Universitätsspital Basel
      • • Klinik für Infektiologie & Spitalhygiene
      • • Neurobiology Unit
      Bâle, Basel-City, Switzerland
  • 2008
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 2007
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany
  • 2005-2007
    • University of Manitoba
      • Faculty of Medicine
      Winnipeg, Manitoba, Canada