Practical applications in immunohistochemistry: Evaluation of rejection and infection in organ transplantation

Context: Immunohistochemical analysis of tissue biopsy specimens is a crucial tool in diagnosis of both rejection and infection in patients with solid organ transplants. In the past 15 years, the concept of antibody-mediated rejection has been refined, and diagnostic criteria have been codified in renal, heart, pancreas, and lung allografts (with studies ongoing in liver, small intestine, and composite grafts), all of which include immunoanalysis for the complement split product C4d. Objectives: To review the general concepts of C4d biology and immunoanalysis, followed by organ-allograftspecific data, and interpretative nuances for kidney, pancreas, and heart, with discussion of early literature for lung and liver biopsies. Additionally, practical applications and limitations of immunostains for infectious organisms (Polyomavirus, Adenoviridae [adenovirus], and the herpes virus family, including Herpes simplex virus, Cytomegalovirus, Human herpes virus 8, and Epstein-Barr virus) are reviewed in the context of transplant recipients. Data Sources: Our experience and published primary and review literature. Conclusions: Immunohistochemistry continues to have an important role in transplant pathology, most notably C4d staining in assessment of antibody-mediated rejection and assessment of viral pathogens in tissue. In all facets of transplant pathology, correlation of morphology with special studies and clinical data is critical, as is close communication with the transplant team.