Role of Pretransplant Complement-fixing Donor-specific Antibodies Identified by C1q Assay in Kidney Transplantation

Thammanichanond, Duangtawan; Wiwattanathum, Punlop; Mongkolsuk, T; Kantachuvesiri, S.; Worawichawong, Suchin; Vallipakorn, Sakda Arj-Ong; Kitpoka, Pimpun

doi:10.1016/j.transproceed.2015.12.116

Cited by 22 publications

(16 citation statements)

References 18 publications

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“…Importantly, one of the largest studies evaluating complement-fixating DSAs with poor graft survival found clinical significance only in the posttransplantation period (17). Pretransplantation correlation was not seen in that study or in several others (20,21).…”

Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 75%

“…Published studies have been inconsistent, with some reporting strong associations between complement fixation and poor allograft outcome (17)(18)(19), while others found no correlations (20,21). SAB assays were modified to assess which, if any, HLA antibodies in patient sera bound specific complement components (C1q, C3d, C4d) as a surrogate of complement activation in vivo.…”

Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 99%

“…SAB assays were modified to assess which, if any, HLA antibodies in patient sera bound specific complement components (C1q, C3d, C4d) as a surrogate of complement activation in vivo. Published studies have been inconsistent, with some reporting strong associations between complement fixation and poor allograft outcome (17)(18)(19), while others found no correlations (20,21). Importantly, one of the largest studies evaluating complement-fixating DSAs with poor graft survival found clinical significance only in the posttransplantation period (17).…”

Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 99%

See 2 more Smart Citations

The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Sullivan

Liwski

Bray

et al. 2017

American Journal of Transplantation

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Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid-phase single-antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring, and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions.

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Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 75%

Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 99%

Section: Merge: "Functional" Methods To Assess Antibody Pathogenicitymentioning

confidence: 99%

See 1 more Smart Citation

The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Sullivan

Liwski

Bray

et al. 2017

American Journal of Transplantation

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“…By contrast, Thammanichanond et al (66) were unable to show a significant effect of CB antibodies with rejection, albeit it in a relatively small cohort of patients. They did however show that the CB antibodies had higher levels of MFI than NCB antibodies.…”

Section: Interpretive Challenges Associated With the Luminex® Bead Assaymentioning

confidence: 79%

Detection of HLA Antibodies in Organ Transplant Recipients – Triumphs and Challenges of the Solid Phase Bead Assay

Tait

2016

Front. Immunol.

113

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This review outlines the development of human leukocyte antigen (HLA) antibody detection assays and their use in organ transplantation in both antibody screening and crossmatching. The development of sensitive solid phase assays such as the enzyme-linked immunosorbent assay technique, and in particular the bead-based technology has revolutionized this field over the last 10–15 years. This revolution however has created a new paradigm in clinical decision making with respect to the detection of low level pretransplant HLA sensitization and its clinical relevance. The relative sensitivities of the assays used are discussed and the relevance of conflicting inter-assay results. Each assay has its advantages and disadvantages and these are discussed. Over the last decade, the bead-based assay utilizing the Luminex® fluorocytometer instrument has become established as the “gold standard” for HLA antibody testing. However, there are still unresolved issues surrounding this technique, such as the presence of denatured HLA molecules on the beads which reveal cryptic epitopes and the issue of appropriate fluorescence cut off values for positivity. The assay has been modified to detect complement binding (CB) in addition to non-complement binding (NCB) HLA antibodies although the clinical relevance of the CB and NCB IgG isotypes is not fully resolved. The increase sensitivity of the Luminex® bead assay over the complement-dependent cytotoxicity crossmatch has permitted the concept of the “virtual crossmatch” whereby the crossmatch is predicted to a high degree of accuracy based on the HLA antibody specificities detected by the solid phase assay. Dialog between clinicians and laboratory staff on an individual patient basis is essential for correct clinical decision making based on HLA antibody results obtained by the various techniques.

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“…С другой стороны, применение сверхчувствитель-ной методики Luminex позволяет идентифициро-вать самые малые концентрации анти-HLA антител, что может приводить к ошибочному завышению реально существующих иммунологических рис-ков. Несмотря на дальнейшее развитие технологий мультиплексного анализа, которые позволили диф-ференцировать анти-HLA антитела в зависимости от подкласса IgG [53] и способности активировать систему комплемента [54], проведенный анализ ма-лых серий наблюдений дал противоречивые резуль-таты [55,56], а целесообразность учета получаемой информации в принятии клинических решений на сегодняшний день не ясна.…”

Section: иммунологические аспекты повторной трансплантации почкиunclassified

Repeat Kidney Transplantation

Сушков

2017

RJTAO

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ФГБУ «Федеральный научный центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России, Москва, Российская Федерация В настоящее время для большинства пациентов с терминальной почечной недостаточностью пересад-ка почки является наилучшим методом заместительной почечной терапии (ЗПТ), который значительно увеличивает продолжительность и качество жизни. Прогресс в области органного донорства, хирурги-ческой техники, трансплантационной иммунологии и иммуносупрессии существенно улучшил непос-редственные результаты трансплантаций. При этом отдаленная выживаемость трансплантатов в течение последних двух десятилетий практически не изменилась. Несоответствие между показателями отдален-ной выживаемости реципиентов и трансплантатов привело к увеличению количества пациентов, утра-тивших функцию пересаженной почки. Для большинства из них повторная трансплантация представля-ется оптимальным вариантом продолжения ЗПТ, хотя и сопряжена c большей частотой осложнений. При этом рекомендации по проведению ретрансплантации почки, основанные на принципах доказательной медицины, до сих пор отсутствуют. Настоящий обзор основан на материале 100 научных публикаций, посвященных различным аспектам планирования и выполнения ретрансплантации почки. Nowadays, kidney transplantation is the best approach of renal replacement therapy for the majority of patients with end-stage renal disease that signifi cantly improves the quality and length of life. Advances in the fi eld of organ donation, immunosuppression, transplant surgery and immunology have improved short-term graft and patient survival. But the long-term graft survival remains static over last two decades. The disparity between low graft and high patient long-term survival led to increasing number of transplant recipients with failed grafts. Repeat renal transplant is presumed to be a good option for many patients losing their grafts, but it is associated with higher complication rates. Unfortunately, there are no evidence-based recommendations or guidelines for renal retransplantation procedure. This review is based on 100 scientifi c publications related to various aspects of the kidney retransplantation and provides the recent data on this matter. Key words: kidney transplantation, kidney retransplantation, graft failure, graft rejection, immunosuppression.Для корреспонденции: Сушков Александр Игоревич. Адрес: 123182, Москва, ул. Щукинская, д. ВВЕДЕНИЕВ течение последних десятилетий транспланта-ция почки остается оптимальным методом замес-тительной почечной терапии, обеспечивающим по сравнению с лечением диализом лучшую продол-жительность и качество жизни пациентов. По дан-ным актуального регистра ERA-EDTA, пятилетняя выживаемость пациентов при лечении гемо-или перитонеальным диализом составляет 40,6%, а пос-ле пересадки почки от живого или трупного доно-ра -94,3 и 87,1% соответственно [1]. Несмотря на столь впечатляющие результаты, следует признать, что функционирование трансплантата в течение 20 и более лет -ситуация скорее уникальная, чем обычная...

show abstract

Role of Pretransplant Complement-fixing Donor-specific Antibodies Identified by C1q Assay in Kidney Transplantation

Cited by 22 publications

References 18 publications

The Road to HLA Antibody Evaluation: Do Not Rely on MFI

The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Detection of HLA Antibodies in Organ Transplant Recipients – Triumphs and Challenges of the Solid Phase Bead Assay

Repeat Kidney Transplantation

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