Pre-Transplant Panel Reactive Antibody in Lung Transplant Recipients is Associated with Significantly Worse Post-Transplant Survival in a Multicenter Study

Hadjiliadis, Denis; Chaparro, Cecilia; Reinsmoen, Nancy L.; Gutiérrez, C.; Singer, Lianne G.; Steele, Mark P.; Waddell, Thomas K.; Davis, Robert D.; Hutcheon, Michael; Palmer, Scott M.; Keshavjee, Shaf

doi:10.1016/j.healun.2004.06.022

Cited by 107 publications

(81 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ability to detect complement deposition and activation using C4d staining has increased the awareness of humoral immune mechanism in the pathogenesis of both acute as well as chronic rejection (19,20). Development of Abs against the donor-mismatched HLA Ags has been shown to correlate with the development of chronic rejection in transplant recipients, and the development of Ab has been shown to precede clinical evidence of chronic rejection (12,21). Studies from our laboratory (11) and others (22)(23)(24) have demonstrated that posttransplant development of anti-HLA Abs correlate with development of BOS following human lung transplantation.…”

Section: Discussionmentioning

confidence: 99%

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

Goers¹,

Ramachandran²,

Aloush

et al. 2008

The Journal of Immunology

181

197

View full text Add to dashboard Cite

Lung transplantation is the treatment option for a variety of end-stage pulmonary diseases. Posttransplant development of Abs against donor HLA and non-HLA Ags have been associated with acute and chronic rejection of transplanted organs. Development of bronchiolitis obliterans syndrome (BOS) following lung transplantation has been correlated with de novo production of anti-donor-HLA Abs. However, only a portion of the patients with BOS demonstrate detectable anti-donor-HLA Abs. Airway epithelium is considered as a major target for lung allograft rejection. In this study we demonstrate that many BOS+ patients (12 of 36) develop Abs reactive to epithelial cell Ag that are distinct from HLA. Furthermore, de novo production of antiepithelial cell Ab precedes clinical onset of BOS. N-terminal sequencing and blastx analysis as well as blocking with K-α1 tubulin-specific Ab identified the epithelial Ag as K-α1 tubulin. Binding of the de novo-produced anti-K-α1 tubulin Abs to the airway epithelial cells resulted in the increased expression of transcription factors (TCF5 and c-Myc), leading to increased expression of fibrogenic growth factors, activation of cell cycle signaling, and fibroproliferation, the central events in immunopathogenesis of BOS following human lung transplantation.

show abstract

Section: Discussionmentioning

confidence: 99%

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

Goers¹,

Ramachandran²,

Aloush

et al. 2008

The Journal of Immunology

181

197

View full text Add to dashboard Cite

show abstract

“…These preexisting or de novo antibodies can react with antigens that are expressed on donor organ cells, leading to immediate graft loss (hyperacute rejection), accelerated AMR, and/or BOS. 26 In fact, studies have consistently demonstrated an increased incidence of acute rejection, 27 persistent rejection, BOS, 28 or worse overall survival 29 in patients with anti-HLA antibodies. Although the optimal treatment of AMR in lung is currently not known owing to difficulties in making the diagnosis and lack of clinical trials, treatment typically includes plasmapheresis, and occasionally, intravenous immunoglobulin or immunomodulatory medications such as rituximab and bortezomib, among others.…”

Section: Diagnosis Of Antibody-mediated Rejection Inmentioning

confidence: 99%

Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society

Roden¹,

Aisner²,

Allen³

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.— The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. Objective.— To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. Data Sources.— Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). Conclusions.— Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.

show abstract

“…19 It can be difficult to find suitable donors for recipients with high levels of circulating preformed antibodies to human leukocyte antigens (HLAs), resulting in prolonged waiting times.…”

Section: Preformed Circulating Antibodiesmentioning

confidence: 99%

Current status of lung transplantation

2012

View full text Add to dashboard Cite

Lung transplantation is a well-established treatment option for selected patients with end-stage lung disease, leading to improved survival and improved quality of life. The last 20 years have seen a steady growth in number of lung transplantation procedures performed worldwide. The increase in clinical activity has been associated with tremendous progress in the understanding of cellular and molecular processes that limit both short-and long-term outcomes. This review gives a comprehensive overview of the current status of lung transplantation for the referring physician. It demonstrates that careful selection of potential recipients, optimisation of their condition prior to transplant, use of carefully assessed donor organs, excellent surgery and meticulous longterm follow-up are all essential ingredients in determining a successful outcome.

show abstract

Pre-Transplant Panel Reactive Antibody in Lung Transplant Recipients is Associated with Significantly Worse Post-Transplant Survival in a Multicenter Study

Cited by 107 publications

References 28 publications

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

De Novo Production of K-α1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection

Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society

Current status of lung transplantation

Contact Info

Product

Resources

About