Effect of desensitization in solid organ transplant recipients depends on some cytokines genes polymorphism

Lobashevsky, Andrew L.; Manwaring, Janel; Travis, Miranda; Nord, Brittany; Higgins, Nasra; Serov, Youri A.; Arnoff, T.S.; Hommel-Berrey, G; Goggins, William C.; Taber, Tim E.; Carter, C.B.; Smith, Daniel; Wozniak, Thomas; O’Donnell, Jacqueline; Turrentine, Mark W.

doi:10.1016/j.trim.2009.03.002

Cited by 12 publications

(5 citation statements)

References 51 publications

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“…[66][67][68] Several studies have underscored that the desensitization effect, with IVIG and plasmapheresis, also depends on the polymorphism of genes encoding INF-γ, IL-2, and IL-4Rα proteins. 69 These findings suggest that cytokine polymorphisms and anti-HLA antibody analyses would be important to identify potential resistance to desensitization treatment and determine the appropriate therapeutic approach.…”

Section: Classic Approaches On Sensitized Patientsmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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Sensitized candidates for heart transplant usually end up on a long waiting list and have an increased risk of rejection, graft loss, and incidence of cardiac allograft vasculopathy. An increasing number of studies have demonstrated the negative effect of preformed and posttransplant antibodies on graft survival. Thus, in sensitized patients, the combination of new, appropriate, desensitization protocols, and monitoring of posttransplant development of donor-specific antibodies may improve short-term and long-term outcomes. Introduction of more-sensitive and more-specific techniques for antibody detection provides a valid tool for assessing the degree of pretransplant HLA histocompatibility, and, therefore, predicting the results of crossmatch in sensitized patients, which are difficult to transplant. Currently, there are no accurate and standard methods to determine the functional characteristics of antibodies detected by solid-phase assay and, therefore, to predict their clinical relevance. Therefore, the future of heart transplantation requires a better understanding of tissue typing techniques and the effect of anti-HLA antibodies on clinical outcome to prevent discrimination against sensitized patients at the time of organ allocation.

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Section: Classic Approaches On Sensitized Patientsmentioning

confidence: 99%

Current Concepts in Histocompatibility During Heart Transplant

Picascia

Grimaldi²,

Zullo³

et al. 2012

Exp Clin Transplant

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“…[1][2][3][4][5][6][7][8][9][10] The popularity of the MBA is the result of 1) the relative ease of covalently coupling of an analyte-capture ligand to spectrally classified carboxylated microspheres; 2) the simultaneous collection of multiple data points from a single specimen, eliminating the one-data point per well enzyme-linked immunosorbent assay (ELISA); 3) the direct proportionality of the fluorescence intensity of the reporter fluorochrome to the amount of captured analyte; and 4) the use of a 96-well format with up to 100 differently classified beads per well, which yield a potential of 9,600 data points per plate. These attractive features of the MBA conserve specimens and save on labor, time, and cost when compared with the ELISA format.…”

Section: Introductionmentioning

confidence: 99%

Multiplex Bead Assay for Serum Samples from Children in Haiti Enrolled in a Drug Study for the Treatment of Lymphatic Filariasis

Moss¹,

Priest²,

Boyd³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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A multiplex bead assay (MBA) was used to analyze serum samples collected longitudinally from children enrolled in a drug trial for treatment of filariasis in Leogane, Haiti. Recombinant antigens Bm14 and Bm33 from Brugia malayi, third polar tube protein (PTP3) from Encephalitozoon cuniculi, and merozoite surface protein-119 (MSP-119) from Plasmodium falciparum were coupled to carboxylated polystyrene microspheres. IgG responses to PTP3 and MSP-119 were not affected by albendazole (ALB), diethylcarbamazine (DEC), or combination of diethylcarbamazine and albendazole (DEC/ALB). However, IgG and IgG4 responses to Bm14 and Bm33 were significantly decreased (P < 0.001) by DEC and DEC/ALB treatment. Antibody responses to Bm14 and Bm33 decreased after DEC treatment (but not placebo) among children who were negative for microfilaremia and antigenemia at baseline, suggesting that these children harbored early stages of infection. The MBA is an excellent serologic technique for multiple antigens that offers substantial advantages over single-antigen based enzyme-linked immunosorbent assay in mass drug administration studies for monitoring changes in antibody levels.

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“…Additionally, from our data, it is impossible to tell prior to treatment which patients may respond to immunomodulation. This likely may be due to complexity of regulatory mechanisms of immune response including hormonal background, chemokine and cytokine gene polymorphism, and frequency of immunoregulatory cells such as B10, NKT cells, and T regulatory cells . Nevertheless, despite the apparent lack of a durable effect, in some patients, the use of this protocol does lower the c‐PRA, if only for a time, thereby making the likelihood of transplantation during this period more likely.…”

Section: Discussionmentioning

confidence: 99%

The effectiveness of the combination of rituximab and high‐dose immunoglobulin in the immunomodulation of sensitized kidney transplant candidates

Taber

Mujtaba

Goggins

et al. 2013

Clinical Transplantation

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Kidney transplantation faces many challenges not the least of which is the presence of pre-formed HLA antibodies. At our institution, we have used a combination of methods to immunomodulate sensitized patients. Most recently, this has been attempted with a combination of immunoglobulin (IVIG) and rituximab (Rituxan; Genetech, CA, USA). A total of 31 patients were followed for up to one yr following treatment with IVIG (2 gm/kg on day 1 and day 30) and rituximab (1 g - day 15). Antibody levels were followed serially at designated time points via solid-phase single-antigen beads (SAB) method (One Lambda, Inc., Canoga Park, CA, USA). Concentration of antibodies was based on median fluorescence intensity (MFI). The majority of patients had both class I and class II antibodies (79%). Our results showed that this protocol appeared to be patient and antibody specific. The most pronounced MFI reduction in antibodies occurred within the 30- to 100-d period post-treatment. Calculated panel-reactive antibodies decreased but rebound tended to occur by 104 d after antibody MFI nadir. Because of this rebound, it can be inferred that the patients did not show a durable increase in their potential for transplantation. The search for a more effective method to immunomodulate patients continues.

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Effect of desensitization in solid organ transplant recipients depends on some cytokines genes polymorphism

Cited by 12 publications

References 51 publications

Current Concepts in Histocompatibility During Heart Transplant

Current Concepts in Histocompatibility During Heart Transplant

Multiplex Bead Assay for Serum Samples from Children in Haiti Enrolled in a Drug Study for the Treatment of Lymphatic Filariasis

The effectiveness of the combination of rituximab and high‐dose immunoglobulin in the immunomodulation of sensitized kidney transplant candidates

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