Thoracic organ transplantation

Pierson, Richard N.; Barr, Mark L.; McCullough, Keith; Egan, Thomas M.; Garrity, Edward R.; Jessup, Mariell; Murray, Susan

doi:10.1111/j.1600-6135.2004.00401.x

Cited by 66 publications

(50 citation statements)

References 25 publications

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“…Both the latter organs suffer the disadvantage of having ongoing exposure to the environment, thus they strongly rely on their organ-specific innate immunity for protection from the environmental noxious agents (46)(47)(48)(49). Important components of the lung-specific innate immune defense mechanisms are provided by pulmonary surfactant phospholipids and the pulmonary surfactant associated proteins.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Reflux and Bile Acid Aspiration on the Lung Allograft and Its Surfactant and Innate Immunity Molecules SP-A and SP-D

D’Ovidio

Mura

Ridsdale

et al. 2006

American Journal of Transplantation

170

116

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Gastro-esophageal reflux and related pulmonary bile acid aspiration were prospectively investigated as possible contributors to postlung transplant bronchiolitis obliterans syndrome (BOS). We also studied the impact of aspiration on pulmonary surfactant collectin proteins SP-A and SP-D and on surfactant phospholipids-all important components of innate immunity in the lung. Proximal and distal esophageal 24-h pH testing and broncho-alveolar lavage fluid (BALF) bile acid assays were performed prospectively at 3-month posttransplant in 50 patients. BALF was also assayed for SP-A, SP-D and phospholipids expressed as ratio to total lipids: phosphatidylcholine; dipalmitoylphosphatidylcholine; phosphatidylglycerol (PG); phosphatidylinositol; sphingomyelin (SM) and lysophosphatidylcholine. Actuarial freedom from BOS was assessed.Freedom from BOS was reduced in patients with abnormal (proximal and/or distal) esophageal pH findings or BALF bile acids (Log-rank Mantel-Cox p < 0.05). Abnormal pH findings were observed in 72% (8 of 11) of patients with bile acids detected within the BALF. BALF with high levels of bile acids also had significantly lower SP-A, SP-D, dipalmitoylphosphatidylcholine; PG and higher SM levels (Mann-Whitney, p < 0.05). Duodeno-gastro-esophageal reflux and consequent aspiration is a risk factor for the development of BOS postlung transplant. Bile acid aspiration is associated with impaired lung allograft innate immunity manifest by reduced surfactant collectins and altered phospholipids.

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Section: Discussionmentioning

confidence: 99%

The Effect of Reflux and Bile Acid Aspiration on the Lung Allograft and Its Surfactant and Innate Immunity Molecules SP-A and SP-D

D’Ovidio

Mura

Ridsdale

et al. 2006

American Journal of Transplantation

170

116

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“…There is growing interest in determining the impact of lung transplantation on functional status and QOL in patients with advanced lung disease (7)(8)(9). Preliminary studies employing standardized QOL questionnaires have reported significant short-and intermediate-term improvements in various QOL measures following lung transplantation (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Association of Clinical Risk Factors with Functional Status Following Lung Transplantation

Sager

Kotloff

Ahya

et al. 2006

American Journal of Transplantation

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A fundamental goal of lung transplantation is the regaining of functional capacity, yet little is known about what factors are associated with the achievement of this goal. The aim of this study is to test the association of clinical risk factors with functional status 1 year following lung transplantation. We conducted a cohort study of 321 lung transplants and assessed functionality by the distance achieved during a standard 6-min walk test (6MWT). Preoperative recipient risk factors were evaluated for association with functional status and adjusted for confounding using multivariable linear regression models. In these multivariable analyses, recipient female gender (p < 0.001), recipient pretransplant body mass index (BMI) of greater than 27 kg/m 2 (p = 0.017) and shorter pretransplant 6MWT distances (p = 0.006) were independently associated with shorter distances achieved during 6MWT after lung transplant, while cystic fibrosis (CF) (p = 0.003), and bilateral lung transplant (p = 0.014) were independently associated with longer distances achieved. Approximately 51% of the variance in 6MWT distance was explained by these risk factors in the linear regression models (R 2 = 0.51). These findings may have implications in patient counseling, selection, procedure choice, and may lead to interventions aimed at improving the functional outcomes of lung transplantation.

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“…For example, over 50% of human cardiac allograft recipients and 80% of lung recipients exhibit chronic rejection within 10 years. Recent additions to the clinical immunosuppressive armamentarium, such as blocking (1) or depleting antibodies (2) and pharmacologic inhibitors (3), have had little appreciable impact on this phenomenon (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys

Kelishadi¹,

Azimzadeh²,

Zhang³

et al. 2010

J. Clin. Invest.

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Chronic rejection currently limits the long-term efficacy of clinical transplantation. Although B cells have recently been shown to play a pivotal role in the induction of alloimmunity and are being targeted in other transplant contexts, the efficacy of preemptive B cell depletion to modulate alloimmunity or attenuate cardiac allograft vasculopathy (CAV) (classic chronic rejection lesions found in transplanted hearts) in a translational model has not previously been described. We report here that the CD20-specific antibody (αCD20) rituximab depleted CD20 + B cells in peripheral blood, secondary lymphoid organs, and the graft in cynomolgus monkey recipients of heterotopic cardiac allografts. Furthermore, CD20 + B cell depletion therapy combined with the calcineurin inhibitor cyclosporine A (CsA) prolonged median primary graft survival relative to treatment with αCD20 or CsA alone. In animals treated with both αCD20 and CsA that achieved efficient B cell depletion, alloantibody production was substantially inhibited and the CAV severity score was markedly reduced. We conclude therefore that efficient preemptive depletion of CD20 + B cells is effective in a preclinical model to modulate pathogenic alloimmunity and to attenuate chronic rejection when used in conjunction with a conventional clinical immunosuppressant. This study suggests that use of this treatment combination may improve the efficacy of transplantation in the clinic. IntroductionThe majority of human allograft recipients develop clinically significant chronic rejection, with incidence and severity increasing steadily over time after transplant. For example, over 50% of human cardiac allograft recipients and 80% of lung recipients exhibit chronic rejection within 10 years. Recent additions to the clinical immunosuppressive armamentarium, such as blocking (1) or depleting antibodies (2) and pharmacologic inhibitors (3), have had little appreciable impact on this phenomenon (4-6).The causes of chronic rejection remain incompletely understood. The classic chronic rejection lesions found in heart (cardiac allograft vasculopathy [CAV]), lung (obliterative bronchiolitis), liver (vanishing bile duct syndrome), and renal (chronic allograft nephropathy) allografts are often temporally associated with detection of anti-donor antibodies, implicating alloantibody as an effector mechanism. Animal models (7-10) and clinical data (11-13) consistently implicate T cell-mediated immunity in the elicited alloantibody response. Thus the current consensus paradigm for chronic rejection holds that T cell-mediated adaptive immunity to alloantigens amplifies innate immune activation initiated by donor brain death and organ ischemia/reperfusion. Influenced in part by the intensity of innate immune activation, T cells propagate pathogenic vascular remodeling and sustain alloantigen-specific chronic inflammation in the transplanted organ. Under the influence

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Thoracic organ transplantation

Cited by 66 publications

References 25 publications

The Effect of Reflux and Bile Acid Aspiration on the Lung Allograft and Its Surfactant and Innate Immunity Molecules SP-A and SP-D

The Effect of Reflux and Bile Acid Aspiration on the Lung Allograft and Its Surfactant and Innate Immunity Molecules SP-A and SP-D

Association of Clinical Risk Factors with Functional Status Following Lung Transplantation

Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys

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