C3d and C4d Deposition Early After Lung Transplantation

Westall, Glen P.; Snell, Greg I.; McLean, Catriona; Kotsimbos, Tom; Williams, Trevor; Magro, Cynthia

doi:10.1016/j.healun.2008.03.018

« Previous Next »The Journal of Heart and Lung Transplantation
Volume 27, Issue 7 , Pages 722-728, July 2008

C3d and C4d Deposition Early After Lung Transplantation

Glen P. Westall, MD
- Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia
- Reprint requests: Glen Westall, MD, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Commercial Road, Prahran, VIC 3181, Australia. Telephone: +61-3-9076-2405. Fax: +61-3-9076-3601.
Greg I. Snell, MD
- Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia
Catriona McLean, MD
- Department of Pathology, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia
Tom Kotsimbos, MD
- Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia
Trevor Williams, MD
- Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia
Cynthia Magro, MD
- Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York.

Received 6 January 2008; received in revised form 6 January 2008; accepted 27 March 2008. published online 03 June 2008.

Background

Complement staining as a predictor of antibody-mediated rejection (AMR) after lung transplantation continues to be debated.

Methods

In a cohort of 33 lung transplant recipients (LTRs) we assessed early post-transplant (≤3 months) graft deposition of the complement factors C3d and C4d and correlated staining with clinical outcome. A retrospective analysis of allograft C3d and C4d deposition was performed by an experienced histopathologist blinded to clinical outcomes. Biopsies were graded 0 to 3 based on extent of septal capillary complement staining.

Results

Significant C3d and C4d staining (i.e., Grade ≥2 on more than one occasion) was observed in 20 and 11 LTRs, respectively. Complement staining was increased in LTRs with severe primary graft dysfunction or airway infection, but was not associated with acute cellular or chronic rejection, or with morphologic features of AMR. In a sub-group analysis we identified 9 LTRs who developed early bronchiolitis obliterans syndrome (BOS) in the absence of acute cellular rejection or cytomegalovirus reactivation, but they had significant lung allograft C3d/C4d deposition along with corroborative light-microscopic features suggestive of AMR.

Conclusions

Complement activation, as judged by lung allograft deposition of C3d/C4d, is common early post–lung transplant and may be triggered by primary graft dysfunction and/or airway infection, and may play a role in the development of early BOS.