Acute rejection and graft survival in renal transplanted patients with viral diseases

Aiello, Francesca; Calabrese, Fiorella; Rigotti, Paolo; Furian, Lucrezia; Marino, S.; Cusinato, Riccardo; Valente, Marialuisa

doi:10.1038/modpathol.3800033

Cited by 32 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prospective protocols to track viral symptoms and identify virus with polymerase chain reaction-based assays have demonstrated a much higher incidence of respiratory viral infection (0.66-1.56 infections per patient-year of follow-up) (35)(36)(37). Likewise, the detection of viral genomes in human cardiac and renal allografts has been increased using polymerase chain reaction-based technology, and the detection of viral genomes in these allografts is also associated with chronic allograft dysfunction (38)(39)(40)(41).…”

Section: Discussionmentioning

confidence: 99%

IL-12 p80 Is an Innate Epithelial Cell Effector That Mediates Chronic Allograft Dysfunction

Mikols

Yan

Norris

et al. 2006

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Bronchiolitis obliterans syndrome is the leading cause of chronic lung allograft dysfunction. We have demonstrated that respiratory viral infection is a bronchiolitis obliterans syndrome risk factor and virus-dependent injury induces expression of innate airway epithelial genes belonging to the interleukin (IL)-12 family. Thus, we hypothesized that epithelial cell IL-12 family members could mediate lung allograft dysfunction. Objectives: We used mouse and human allograft specimens to evaluate the role of epithelial cell IL-12 family members in allograft dysfunction associated with and without viral infection. Methods: Murine and human IL-12 family members were characterized and manipulated in allografts and then correlated with epithelial cell injury, immune cell accumulation, and collagen deposition. Results: In a mouse model of lung transplantation, concurrent viral infection and allogeneic transplantation increased epithelial injury and this was followed by exaggerated accumulation of macrophages and collagen deposition. This virus-driven allograft dysfunction was associated with an epithelial innate response manifested by a synergistic increase in the production of the macrophage chemoattractant IL-12 p80 (p80), but not IL-12 or IL-23. Blockade or overexpression of donor epithelial p80 resulted in a corresponding abrogation or enhancement of macrophage accumulation and allograft dysfunction. We extended these findings to human recipients with viral infection and transplant bronchitis and again observed excessive epithelial p80 expression that correlated with increased macrophage accumulation. Conclusions: These experiments support a role for an enhanced epithelial innate response as a central process in allograft dysfunction and identify the macrophage chemoattractant p80 as an innate epithelial effector of disease progression.

show abstract

Section: Discussionmentioning

confidence: 99%

IL-12 p80 Is an Innate Epithelial Cell Effector That Mediates Chronic Allograft Dysfunction

Mikols

Yan

Norris

et al. 2006

Am J Respir Crit Care Med

View full text Add to dashboard Cite

show abstract

“…Aielo et al compared histological changes in transplant biopsies in patients with acute rejection, with and without a history of CMV or EBV infection. They noted an increase in plasma cell infiltrates and C4d staining in those with viral infections [64]. CMV infection has also been temporally associated with the development of anti-endothelial cell antibodies in cardiac and renal allograft recipients, with biopsy-proven humoral rejection [65] and with the appearance of anti-islet cell antibodies in pancreas transplant recipients [66].…”

Section: Antigen and Alloantibody Formation In Transplantationmentioning

confidence: 99%

The generation and maintenance of serum alloantibody

Clatworthy

Espéli

Torpey

et al. 2010

Current Opinion in Immunology

View full text Add to dashboard Cite

Donor-specific alloantibodies (DSA) mediate hyperacute and acute antibody-mediated rejection (AMR), which can lead to early graft damage and loss, and are also associated with chronic AMR and reduced long-term graft survival. Such alloantibodies can be generated by previous exposure to major histocompatibility (MHC) antigens (usually via blood transfusions, previous allografts or pregnancy) or can occur de novo after transplantation. Recent studies also suggest that non-MHC antibodies, including those recognising major histocompatibility complex class I-related chain A (MICA), MICB, vimentin, angiotensin II type I receptor may also have an adverse impact on allograft outcomes. In this review, we consider how the dose, route and context of antigen exposure influences DSA induction and describe factors which control the generation, maintenance and survival of alloantibody-producing plasma cells. Finally, we discuss the implications of these variables on therapeutic approaches to DSA.

show abstract

“…Both EpsteinBarr Virus and cytomegalovirus (CMV) are examples of viruses that have been strongly linked to acute and chronic antibodymediated injury through this mechanism in organ transplant recipients. 17 The development of de novo donor-specific antibodies (DSAs) after transplant is now a widely used harbinger of subclinical alloreactivity and often precedes overt antibodymediated rejection by months to years. 18,19 We hypothesized that persistent BK viremia is a risk factor for and precedes the development of DSAs.…”

mentioning

confidence: 99%

Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

Sawinski¹,

Forde²,

Trofe‐Clark³

et al. 2015

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney-pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40-393 days), and persistent BK viremia was defined as lasting $140 days. Kaplan-Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

show abstract

Acute rejection and graft survival in renal transplanted patients with viral diseases

Cited by 32 publications

References 58 publications

IL-12 p80 Is an Innate Epithelial Cell Effector That Mediates Chronic Allograft Dysfunction

IL-12 p80 Is an Innate Epithelial Cell Effector That Mediates Chronic Allograft Dysfunction

The generation and maintenance of serum alloantibody

Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

Contact Info

Product

Resources

About