Significance of Tubuloreticular Inclusions in Renal Allografts M

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Significance of Tubuloreticular Inclusions in Renal Allografts
M.Willicombe, C.Roufosse, L.Moran, J.Moss, D.Taube and T.Cook
Imperial College Kidney and Transplant Centre, Hammersmith Hospital, London, UK
Introduction. Tubuloreticular inclusions [TRIs] are commonly identified by electron microscopy
[EM] in the endothelial cells and lymphocytes of patients with autoimmune diseases and viral
infections such as SLE and HIV. TRIs are pathognomic of α- and β- interferon [IFN] production. The
purpose of this study was to determine the relevance of TRIs in renal transplant biopsies.
Methods. We retrospectively analysed the histology reports of 2803 biopsy specimens from 1138
renal transplant recipients. 448 [16.0%] of samples from 306 patients were examined by EM. 37/306
[12.1%] patients were TRI+ and the remaining 269/306 [87.9%] TRI- patients served as controls.
Mean follow up post index biopsy was 3.93 ± 2.22 years.
Results. Patient survival was inferior in the TRI+ group compared with the TRI- group, 62.1% and
84.4% respectively [p=0.03]. Non-censored allograft survival was also inferior, 43.6% and 61.0% in
the TRI+ and TRI- groups respectively [p=0.02]. Rejection free survival post index biopsy did not
differ at 71.1% and 77.5% in the TRI+ and TRI- groups, p=0.97, although 20/37 [54.1%] TRI+ and
99/269 [36.8%] TRI- index biopsies had features of alloimmune injury, p=0.07. TRI+ patients were
also more likely to have had prior rejection; 14/37 [37.8%] compared with 45/269 [16.7%], p=0.047,
and also have class I DSA, 18/37 [48.6%] and 76/269 [28.3%], p=0.02. Evidence of the classic
associations of TRIs, namely viral infections, autoimmune disease and malignancy were also
investigated by multivariate analysis. Malignancy [OR: 7.08(1.01-49.50), p=0.049], viral infection
[OR: 2.52(1.12-5.64), p<0.001] and DSA [OR: 2.51(1.12-5.62), p=0.025] were found to be associated
with the presence of TRIs.
Conclusion. TRIs in renal transplant biopsies are not common but are associated with inferior patient
and allograft outcomes. Viral infections at the time of biopsy are most strongly associated with TRIs.
The novel finding of this study is that alloimmunity and specifically class I DSA are associated with
TRIs.
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