Pilot Study Exploring Lung Allograft Surfactant Protein A (SP-A) Expression in Association With Lung Transplant Outcome

被引:24
作者
D'Ovidio, F. [1 ]
Kaneda, H. [2 ]
Chaparro, C. [2 ]
Mura, M. [2 ]
Lederer, D. [1 ]
Di Angelo, S. [3 ]
Takahashi, H. [4 ]
Gutierrez, C. [2 ]
Hutcheon, M. [2 ]
Singer, L. G. [2 ]
Waddell, T. K. [2 ]
Floros, J. [3 ,5 ]
Liu, M. [2 ]
Keshavjee, S. [2 ]
机构
[1] Columbia Univ, Med Ctr, Lung Transplant Program, New York, NY USA
[2] Univ Toronto, Toronto Lung Transplant Program, Toronto, ON, Canada
[3] Penn State Univ, Coll Med, Ctr Host Def Inflammat & Lung Dis CHILD Res, Dept Pediat, Hershey, PA USA
[4] Sapporo Med Univ, Sch Med, Dept Internal Med 3, Sapporo, Hokkaido, Japan
[5] Penn State Univ, Coll Med, Ctr Host Def Inflammat & Lung Dis CHILD Res, Dept Obstet & Gynecol, Hershey, PA USA
关键词
Innate immunity; lung transplantation; polymorphism; surfactant protein A; D MARKER ALLELES; PULMONARY SURFACTANT; GENETIC-VARIANTS; INNATE IMMUNITY; MESSENGER-RNA; SP-A2; GENES; GLUCOCORTICOIDS; DISEASE; BIOLOGY; HUMANS;
D O I
10.1111/ajt.12407
中图分类号
R61 [外科手术学];
学科分类号
摘要
Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p<0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p=0.03) and IL-12 (p<0.0001) in the BALF and a greater incidence of rejection episodes (p=0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p=0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p<0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.
引用
收藏
页码:2722 / 2729
页数:8
相关论文
共 30 条
[1]   Methylprednisolone Regulation of Human Donor Lung Surfactant Protein A (SP-A) Expression Is Dependent on the SP-A Polymorphism [J].
Aramini, B. ;
Kim, C. ;
Lederer, D. ;
Costa, J. ;
DiAngelo, S. ;
Floros, J. ;
Arcasoy, S. ;
Sonett, J. ;
D'Ovidio, F. .
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 2012, 31 (04) :S185-S185
[2]   Liver and intestine transplantation [J].
Brown, RS ;
Rush, SH ;
Rosen, HR ;
Langnas, AN ;
Klintmalm, GB ;
Hanto, DW ;
Punch, JD .
AMERICAN JOURNAL OF TRANSPLANTATION, 2004, 4 :81-92
[3]   The effect of reflux and bile acid aspiration on the lung allograft and its surfactant and innate immunity molecules SP-A and SP-D [J].
D'Ovidio, F. ;
Mura, M. ;
Ridsdale, R. ;
Takahashi, H. ;
Waddell, T. K. ;
Hutcheon, M. ;
Hadjiliadis, D. ;
Singer, L. G. ;
Pierre, A. ;
Chaparro, C. ;
Gutierrez, C. ;
Miller, L. ;
Darling, G. ;
Liu, M. ;
Post, M. ;
Keshavjee, S. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (08) :1930-1938
[4]   Novel, non-radioactive, simple and multiplex PCR-cRFLP methods for genotyping human SP-A and SP-D marker alleles [J].
DiAngelo, S ;
Lin, ZW ;
Wang, GR ;
Phillips, S ;
Ramet, M ;
Luo, JM ;
Floros, J .
DISEASE MARKERS, 1999, 15 (04) :269-281
[5]   SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion [J].
Erasmus, ME ;
Hofstede, GJH ;
Petersen, AH ;
Batenburg, JJ ;
Haagsman, HP ;
Oetomo, SB ;
Prop, J .
TRANSPLANTATION, 2002, 73 (03) :348-352
[6]   Genetics of the hydrophilic surfactant proteins A and D [J].
Floros, J ;
Hoover, RR .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1998, 1408 (2-3) :312-322
[7]   Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome [J].
Floros, J ;
Fan, RZ ;
Diangelo, S ;
Guo, XX ;
Wert, J ;
Luo, JM .
PEDIATRICS INTERNATIONAL, 2001, 43 (06) :567-576
[8]   A point of view: quantitative and qualitative imbalance in disease pathogenesis; pulmonary surfactant protein A genetic variants as a model [J].
Floros, J ;
Wang, GR .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY, 2001, 129 (01) :295-303
[9]   The interleukin-12/interleukin-12-receptor system: Role in normal and pathologic immune responses [J].
Gately, MK ;
Renzetti, LM ;
Magram, J ;
Stern, AS ;
Adorini, L ;
Gubler, U ;
Presky, DH .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :495-521
[10]  
Ghanekar A, 2001, Curr Opin Crit Care, V7, P133, DOI 10.1097/00075198-200104000-00013