Neointimal inflammation and adventitial angiogenesis correlate with severity of cardiac allograft vasculopathy in pediatric recipients.
BACKGROUND
Chronic inflammation and angiogenesis have been implicated in the pathogenesis of both cardiac allograft vasculopathy (CAV) and age-related vasculopathy. Because concurrent atherosclerosis does not complicate assessment of CAV in children, we sought to characterize the spectrum of coronary lesions in this population and determine whether inflammatory infiltrates and angiogenesis correlate with severity of CAV.


METHODS
In 18 pediatric heart specimens CAV was graded 1 to 4 (none to severe). Each case was assigned to either: Group I, no inflammation; Group II, perivascular inflammation; or Group III, perivascular and neointimal inflammation. Inflammatory infiltrates were immunophenotyped using anti-CD3, anti-CD20 and HAM 56. Angiogenesis was assessed by determining microvascular density (MVD) in 5 high-power fields (HPFs) per section.


RESULTS
CAV was evident in 94% of cases, and inflammation in 61%. Cases with neointimal inflammation had significantly more severe CAV compared with cases without inflammation (2.7 +/- 0.16 vs 1.9 +/- 0.2, p = 0.002). MVD was significantly higher in both inflammation groups (Groups II and III) compared with Group I (4.1 +/- 0.5 per HPF and 5.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0.018 and p = 0.002) and correlated with the degree of CAV (p = 0.007). The perivascular infiltrates (Group II, n = 5) contained lymphocytes, macrophages and plasma cells, and 67% of neointimal infiltrates (Group III, n = 6) also contained eosinophils.


CONCLUSIONS
CAV in children is more common than previously reported. Our data indicate that CAV is often associated with inflammation and that adventitial angiogenesis correlated with the severity of CAV.
Seipelt
Ingrid M
IM
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Pahl
Elfriede
E
Seipelt
Ralf G
RG
Mavroudis
Constantine
C
Backer
Carl L
CL
Stellmach
Veronica
V
Cornwell
Mona
M
Crawford
Susan E
SE
D000293:Adolescent; D000704:Analysis of Variance; D001707:Biopsy, Needle; D002648:Child; D002675:Child, Preschool; D003327:Coronary Disease / Q000473:pathology*; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009924:Organ Culture Techniques; D011336:Probability; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D014184:Transplantation, Homologous; D017539:Tunica Intima / Q000473:pathology*