In
ter
sti
tial fibro
si
s and
tubular a
trophy (IFTA) i
s found in approxima
tely 25% of 1-year biop
sie
s po
sttran
splan
t. I
t i
s known
tha
t IFTA correla
te
s wi
th decrea
sed graf
t survival when hi
stological evidence of inflamma
tion i
s pre
sen
t. Iden
tifying
the mechani
stic e
tiology of IFTA i
s impor
tan
t to under
standing why long-
term graf
t survival ha
s no
t changed a
s expec
ted de
spi
te improved immuno
suppre
ssion and drama
tically reduced ra
te
s of clinical acu
te rejec
tion (AR) (Service
s UDoHaH.
ttp://www.ustransplant.org/annual_reports/current/509a_ki.htm" title="Link to external resource: http://www.ustransplant.org/annual_reports/current/509a_ki.htm" target="_blank">http://www.ustransplant.org/annual_reports/current/509a_ki.htm). Gene expre
ssion profile
s of 234 graf
t biop
sy
sample
s were ob
tained wi
th ma
tching clinical and ou
tcome da
ta. Eigh
ty-one IFTA biop
sie
s were divided in
to
subpheno
type
s by degree of hi
stological inflamma
tion: IFTA wi
th AR, IFTA wi
th inflamma
tion, and IFTA wi
thou
t inflamma
tion. Sample
s wi
th AR (n = 54) and normally func
tioning
tran
splan
ts (TX; n = 99) were u
sed in compari
son
s. A novel analy
si
s u
sing gene coexpre
ssion ne
twork
s revealed
tha
t all IFTA pheno
type
s were
strongly enriched for dy
sregula
ted gene pa
thway
s and
the
se were
shared wi
th
the biop
sy profile
s of AR, including IFTA
sample
s wi
thou
t hi
stological evidence of inflamma
tion. Thu
s, by molecular profiling we demon
stra
te
tha
t mo
st IFTA
sample
s have ongoing immune-media
ted injury or chronic rejec
tion
tha
t i
s more
sen
si
tively de
tec
ted by gene expre
ssion profiling. The
se molecular biop
sy profile
s correla
ted wi
th fu
ture graf
t lo
ss in IFTA
sample
s wi
thou
t inflamma
tion.