Pretransplant anti-HLA-Cw and anti-HLA-DP antibodies in sensitized patients

Ling, Min; Marfo, Kwaku; Masiakos, Peter T.; Aljanabi, Aws; Lindower, Joel; Glicklich, Daniel; Boccardo, Graciela de; Greenstein, Stuart; Chapochnick-Friedmann, Javier; Kayler, Liise K.; Kinkhabwala, Milan; Akalin, Enver

doi:10.1016/j.humimm.2012.07.320

Cited by 49 publications

(40 citation statements)

References 20 publications

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“…Several studies have reported that pregnancies, blood transfusions and previous transplants are potential risk factors for development of anti-HLA antibodies [6], [20]. The vast majority of patients investigated in the present study had received blood transfusions (59.5%), some patients had received previous transplants (7.4%), and most women had had pregnancies (79.4%).…”

Section: Discussionmentioning

confidence: 58%

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

Saito

Yamakawa

Aparecida³

et al. 2014

PLoS ONE

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Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

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Section: Discussionmentioning

confidence: 58%

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

Saito

Yamakawa

Aparecida³

et al. 2014

PLoS ONE

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“…We analyzed the Luminex data using units of fluorescence intensity, rather than calculated concentrations from standard curves, which allowed analysis of low cytokine levels that were clearly detectable but below the lowest standard. This methodology has been used by some investigators in other fields, 19,20 but most prior HIV-1 studies have used calculated concentrations. Standardizing laboratory techniques has been the focus of working groups such as the Semen Best Practices Working Group at the National Institutes of Health, and will provide much needed guidance for future studies.…”

Section: Discussionmentioning

confidence: 99%

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

Hoffman

Anton

Baldwin

et al. 2014

AIDS Research and Human Retroviruses

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Seminal plasma HIV-1 RNA level is an important determinant of the risk of HIV-1 sexual transmission. We investigated potential associations between seminal plasma cytokine levels and viral concentration in the seminal plasma of HIV-1-infected men. This was a prospective, observational study of paired blood and semen samples from 18 HIV-1 chronically infected men off antiretroviral therapy. HIV-1 RNA levels and cytokine levels in seminal plasma and blood plasma were measured and analyzed using simple linear regressions to screen for associations between cytokines and seminal plasma HIV-1 levels. Forward stepwise regression was performed to construct the final multivariate model. The median HIV-1 RNA concentrations were 4.42 log 10 copies/ml (IQR 2.98, 4.70) and 2.96 log 10 copies/ml (IQR 2, 4.18) in blood and seminal plasma, respectively. In stepwise multivariate linear regression analysis, blood HIV-1 RNA level ( p < 0.0001) was most strongly associated with seminal plasma HIV-1 RNA level. After controlling for blood HIV-1 RNA level, seminal plasma HIV-1 RNA level was positively associated with interferon (IFN)-c ( p = 0.03) and interleukin (IL)-17 ( p = 0.03) and negatively associated with IL-5 ( p = 0.0007) in seminal plasma. In addition to blood HIV-1 RNA level, cytokine profiles in the male genital tract are associated with HIV-1 RNA levels in semen. The Th1 and Th17 cytokines IFN-c and IL-17 are associated with increased seminal plasma HIV-1 RNA, while the Th2 cytokine IL-5 is associated with decreased seminal plasma HIV-1 RNA. These results support the importance of genital tract immunomodulation in HIV-1 transmission.

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“…The patient also had antibodies to donor DP antigens. Ling et al (91) reported on eight patients with antibody to donor Cw antigens, one of which had a positive FCXM while the crossmatch tests of the other seven were negative. The patients were followed for 3–24 months during which there was no antibody-mediated rejection and no graft loss.…”

Section: Hla-matching Strategies For Sensitized Patientsmentioning

confidence: 99%

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Zachary

Leffell

2016

Front. Immunol.

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HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor.

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Pretransplant anti-HLA-Cw and anti-HLA-DP antibodies in sensitized patients

Cited by 49 publications

References 20 publications

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates

Seminal Plasma HIV-1 RNA Concentration Is Strongly Associated with Altered Levels of Seminal Plasma Interferon-γ, Interleukin-17, and Interleukin-5

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

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