Polyomavirus nephropathy (PPT / 3880.5 KB)

January 29, 2018 | Author: Anonymous | Category: Science, Health Science, Immunology
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Polyomavirus nephropathy: updated

Helmut Hopfer, Basel, Switzerland

Agenda • SV40 immunohistochemistry and BK viremia • PVN treatment: implications for morphology • PVN and rejection

How to diagnose PVN?

BK-BIFQUIT: trial design participants SV 40 IHC SV40 IHC

SV40 IHC

participants score intensity and extent

inter-observer variability organizers score intensity and extent

SV40 IHC

SV40 IHC

SV40 IHC

SV40 IHC

SV40 IHC

SV40 IHC

inter-laboratory variability

SV40 IHC: inter-observer variability

Substantial agreement (staining intensity and extent of infection)

unpublished data, M. Mengel, Edmonton

SV40 IHC: inter-laboratory variability

Below chance (staining intensity and extent of infection) Substantial agreement (positive vs. negative cores)

unpublished data, M. Mengel, Edmonton

BK-BIFQUIT: summary • BK "best practice": automated stainer, heat induced epitope retrieval (>30 minutes), either citrate or EDTA buffer, monoclonal antibody (PAB416) 1'000 copies/ml •treated with reduction of maintenance immunosuppression •no rejection therapy •at least 1 surveillance biopsy during BKV

before BKV

increasing BKV

decreasing BKV

after BKV

Morphological assessment, statistical analysis and correlation with clinical data

unpublished data, H. Hopfer, Basel

Resolving PVN (decreasing BKV)

Residual PVN (cleared BKV)

"Tubulitis " and inflammation • During decreasing viremia there was a significant increase in the Banff tubulitis score (t) as well as the extent of interstitial inflammatory infiltrate. • Persistence of intraepithelial lymphocytes and interstitial inflammation after viral clearance.

unpublished data, H. Hopfer, Basel

Creatinine course • Serum creatinine values overall remained stable (baseline 1st replication - peak replication - clearance - last follow up) • Increase of serum creatinine ≥40 umol/l during decreasing viremia in ~40% of patients, which returned to baseline without additional treatment

unpublished data, H. Hopfer, Basel

Summary 2 BKV-specific cellular immunity Blood

Kidney

BK-induced tubular damage BK-induced inflammation anti-BK inflammation and IEL time after transplantation

BK dynamics

PVN

resolving PVN

residual PVN

increasing

decreasing

cleared

PVN and rejection – a matter of faith? • • •

Do you believe in PVN and rejection? Can you distinguish PVN from rejection? How do you treat PVN and rejection?

BK-specific, rejection or "innocent"? • BK-specific lymphocyte? (anti-BK immune response) • HLA-specific lymphocyte? (rejection?) • "innocent" lymphocyte? (unspecific infiltrate)

Distinction PVN and ICR? • SV40 immunohistochemistry? • Severity and extent of tubulitis and inflammation? • Cellular composition of infiltrate?

How to treat PVN and rejection? • Individualize decisions in patients with concurrent vascular or humoral rejections • PVN is more important than ICR

Take-home messages • • • •

PVN is focal, high number of falsly negative cases Resolving PVN is an anti-viral acute interstitial nephritis Give BK-specific immunity a chance Clinicopathological correlation is key to the correct diagnosis (clinical history, viral dynamics, creatinine course, morphological findings)

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