Increasing of the interferon-γ gene expression during polyomavirus BK infection in kidney transplant patients

Zareei, Neda; Miri, H R; Karimi, Mohammad Hossein; Afshari, Afsoon; Geramizadeh, Bita; Roozbeh, Jamshid; Yaghobi, Ramin

doi:10.1016/j.micpath.2019.02.015

Cited by 16 publications

(11 citation statements)

References 36 publications

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“…48 In addition, BK virus can directly injure endothelial cells and promote release of interferon-g. 49 Inflammatory cytokines like IL-6, IL-8, and interferong are also released from circulating activated T cells, NK cells, monocytes, and tissue macrophages as a result of BK virus infection, GVHD and in disorders like hemophagocytic lymphohistiocytosis, with high interferon production resulting in thrombotic microangiopathy. 49,50 Our study has strengths and limitations. Our study benefited from a careful, prospective TA-TMA phenotyping in HSCT recipients using established diagnostic and risk criteria, and our experience using eculizumab in these complex patients.…”

Section: Discussionmentioning

confidence: 99%

Interferon-complement loop in transplant-associated thrombotic microangiopathy

et al. 2020

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Transplant-associated thrombotic microangiopathy (TA-TMA) is an important cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The complement inhibitor eculizumab improves TA-TMA, but not all patients respond to therapy, prompting a search for additional targetable pathways of endothelial injury. TA-TMA is relatively common after HSCT and can serve as a model to study mechanisms of tissue injury in other thrombotic microangiopathies. In this work, we performed transcriptome analyses of peripheral blood mononuclear cells collected before HSCT, at onset of TA-TMA, and after resolution of TA-TMA in children with and without TA-TMA after HSCT. We observed significant upregulation of the classical, alternative, and lectin complement pathways during active TA-TMA. Essentially all upregulated genes and pathways returned to baseline expression levels at resolution of TA-TMA after eculizumab therapy, supporting the clinical practice of discontinuing complement blockade after resolution of TA-TMA. Further analysis of the global transcriptional regulatory network showed a notable interferon signature associated with TA-TMA with increased STAT1 and STAT2 signaling that resolved after complement blockade. In summary, we observed activation of multiple complement pathways in TA-TMA, in contrast to atypical hemolytic uremic syndrome (aHUS), where complement activation occurs largely via the alternative pathway. Our data also suggest a key relationship between increased interferon signaling, complement activation, and TA-TMA. We propose a model of an “interferon-complement loop” that can perpetuate endothelial injury and thrombotic microangiopathy. These findings open opportunities to study novel complement blockers and combined anti-complement and anti-interferon therapies in patients with TA-TMA and other microangiopathies like aHUS and lupus-associated TMAs.

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Section: Discussionmentioning

confidence: 99%

Interferon-complement loop in transplant-associated thrombotic microangiopathy

et al. 2020

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“…4). Pooled prevalence of BKV from 5 cities among Iranian population was as follows: 4 studies from Tehran (22%, I 2 = 81%, p < 0.01) [17, 18, 25, 30], 4 studies from Shiraz (18%, I 2 = 93%, p < 0.01) [19, 20, 22, 23], 1 study from Ahvaz (42%) [28], 3 studies from Urmia (14%, I 2 = 62%, p = 0.07) [24, 26, 27], and 1 study from Guilan (49%) [21] (Fig. 5).…”

Section: Resultsmentioning

confidence: 99%

“…The majority of articles analyzed plasma sample alone or in combination with other type of specimens. Two studies solely used biopsy tissues [24, 25], 2 studies solely used plasma [20, 22, 23], 5 studies used a combination of plasma and urine [17, 18, 21, 28, 29], 1 study used plasma plus biopsy tissue [19], 1 study used serum plus urine [30], and 2 study used urine alone [26, 27]. Overall, the prevalence of BKV in plasma was (16%, I 2 = 86%, p < 0.01), in renal biopsies was (10%, I 2 = 71%, p = 0.03) [19, 24, 25], and in urine was (29%, I 2 = 88%, p < 0.01) [17, 18, 21, 26, 27, 29, 30] (Fig.…”

Section: Resultsmentioning

confidence: 99%

Survey of BK Virus in Renal Transplant Recipients in Iran: A Systematic Review and Meta-Analysis

et al. 2020

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Introduction: BK virus (BKV) infection in renal transplant (RT) recipients can cause hemorrhagic cystitis, transient renal dysfunction, and BKV nephropathy (BKVN). The prevalence and significance of BKV in RT recipients remain to be clarified in the Iranian population. The purpose of this review is to summarize the overall prevalence of BKV infection in RT recipients from previously published studies in Iran. Methods: We systematically reviewed articles through a comprehensive search of the main electronic and Persian national databases up to November 2019. Results: The overall pooled prevalence of BKV infection among the Iranian population was 23% (95% CI; 15–33%). Comparing these studies revealed that the prevalence of BKV in plasma samples ranges from 3 to 40%, in renal biopsies 1–13%, and in urine samples 10–49%. Due to substantial heterogeneity among reported studies (I2 = 93%, p < 0.01), random-effect meta-analysis was performed. BKV infection rate was slightly higher in women than men (16%, p = 0.04 vs. 14%, p < 0.01, respectively). The majority of the studies employed real-time PCR (24%, I2 = 93, p < 0.01) and analyzed plasma samples alone or in combination with other types of specimens. BKV prevalence from 5 cities among the Iranian population showed a higher prevalence rate in Guilan. Conclusion: Our analysis provides a preliminary estimate of the epidemiology of BKV infection in RT recipients in Iran. These results arouse a need for more epidemiological studies of BKV infection in different unanalyzed regions in Iran. Early detection of BKV in RT recipients helps timely nephropathy diagnosis and prevents graft loss.

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“…Studies of urinary chemokines, including CXCL9 and CXCL10, have shown potential benefit and correlate with our own centre experience. Similarly, urine exosomal microRNA signatures, urine proteinase inhibitor 9 (PI 9) mRNA, cellular assays for IFN‐gamma, and plasma donor‐derived cell‐free DNA have all demonstrated the ability to differentiate between various immune‐mediated causes of transplant dysfunction. Furthermore, developments in urine proteomic profiling from Pittsburgh show promise in differentiating BKVN from acute rejection .…”

Section: Diagnostic Challengesmentioning

confidence: 99%

BK virus: Current understanding of pathogenicity and clinical disease in transplantation

Chong

Antoni

Macdonald

et al. 2019

Reviews in Medical Virology

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BK polyomavirus (BKV) is an important cause of graft loss in renal transplant recipients that continues to pose a significant challenge to clinicians due to its frequently unpredictable onset, persistence, and the lack of effective antiviral agents or prevention strategies. This review covers our current understanding of epidemiology, viral transmission and disease progression, and treatment and prevention strategies that have been used to manage this disease.

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Increasing of the interferon-γ gene expression during polyomavirus BK infection in kidney transplant patients

Cited by 16 publications

References 36 publications

Interferon-complement loop in transplant-associated thrombotic microangiopathy

Interferon-complement loop in transplant-associated thrombotic microangiopathy

Survey of BK Virus in Renal Transplant Recipients in Iran: A Systematic Review and Meta-Analysis

BK virus: Current understanding of pathogenicity and clinical disease in transplantation

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