Update on pathology of antibody-mediated rejection in the lung allograft

Wallace, W. Dean; Weigt, S. Sam; Farver, Carol

doi:10.1097/mot.0000000000000079

Cited by 31 publications

(35 citation statements)

References 36 publications

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“…Hematoxylin and eosin sections were analyzed for the presence of ACR and subsequently graded as defined by ISHLT (30). The following histological patterns compatible with AMR were also analyzed: (i) neutrophil capillaritis and (ii) acute lung injury with or without diffuse alveolar damage and with or without organizing pneumonia (19,20). The presence of DSAs, clinical dysfunction or histological pattern suggestive of AMR was further characterized by C4d immunohistochemical stains performed on formalin-fixed, paraffin-embedded tissue sections.…”

Section: Patient Categorization and Amr-dsa Statusmentioning

confidence: 99%

“…Despite these previous publications, there is currently no widely accepted definition of AMR in LT (19,20). Uncertainty of diagnostic criteria leads numerous studies to demonstrate the association of DSAs and LT prognosis while circumventing discussion regarding the role of AMR in LT outcome.…”

Section: Introductionmentioning

confidence: 99%

“…According to the most recent International Society for Heart and Lung Transplantation (ISHLT) update (19), the diagnosis of pulmonary AMR requires a multidisciplinary approach that includes the presence of clinical allograft dysfunction, circulating DSAs, and explicit pathologic findings. Because of lack of specificity and technical difficulties, not only is C4d staining cautiously interpreted, its inclusion in AMR diagnosis remains a matter of debate (20).…”

Section: Introductionmentioning

confidence: 99%

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Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

Roux

Lan

Holifanjaniaina

et al. 2016

American Journal of Transplantation

119

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Section: Patient Categorization and Amr-dsa Statusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

Roux

Lan

Holifanjaniaina

et al. 2016

American Journal of Transplantation

119

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“…Our observations are in keeping with those in an acute rat renal transplant model in which a Syk inhibitor improved acute rejection by suppressing allograft infiltration with neutrophils (33). Neutrophils are thought to be important effectors of antibody-mediated allograft injury and rejection (56) and are implicated in acute and chronic lung allograft dysfunction (57,58).…”

Section: Sykmentioning

confidence: 99%

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation

Matsuda

Wang

Oishi

et al. 2016

American Journal of Transplantation

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Chronic lung allograft dysfunction, the major cause of death following lung transplantation, usually manifests as irreversible airflow obstruction associated with obliterative bronchiolitis (OB), a lesion characterized by chronic inflammation, lymphoid neogenesis, fibroproliferation and small airway obliteration. Spleen tyrosine kinase (Syk), a tyrosine kinase that regulates B cell function and innate immunity, has been implicated in the pathogenesis of chronic inflammation and tissue repair. This study evaluated the role of Syk in development of OB, using an intrapulmonary tracheal transplant model of OB with the conditional Syk-knockout Syk flox/flox // rosa26-CreER T2 mice and a Syk-selective inhibitor, GSK2230413. BALB/c trachea allografts were transplanted into Syk-knockout (Syk del/del ) mice or wild-type C57BL/6 recipients treated with GSK2230413. At day 28, histological analysis revealed that in the Syk del/del and GSK2230413-treated C57BL/6 recipients, the graft lumen remained open compared with allografts transplanted into Syk-expressing (Syk flox/flox ) and placebo controltreated C57BL/6 recipients. Immunofluorescence showed lymphoid neogenesis with distinct B and T cell zones in control mice. In contrast, lymphoid neogenesis was absent and few B or T cells were found in Syk del/del and GSK2230413-treated mice. These observations suggest that inhibition of Syk may be a potential therapeutic strategy for the management of OB following lung transplantation.Abbreviations: BOS, bronchiolitis obliterans syndrome; CLAD, chronic lung allograft dysfunction; IPTT, intrapulmonary tracheal transplant; MC, methylcellulose; OB, obliterative bronchiolitis; PBS, phosphate-buffered saline; PNAd, peripheral node addressin; Syk, spleen tyrosine kinase

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“…Several primary studies reviewed in the summary statement, along with studies published since then, recognize that the correlation of C4d staining and donor-specific antibody studies in lung allografts may be loose, if not controversial, and will certainly require further study. 14,[77][78][79][80][81] Currently, analogous to other solid organ allografts, it is recommended that C4d staining in allograft lung tissue be scored in the interstitial alveolar capillaries only.…”

Section: Lungmentioning

confidence: 99%

Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation

Troxell¹,

Lanciault

2016

Archives of Pathology &Amp; Laboratory Medicine

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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.

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Update on pathology of antibody-mediated rejection in the lung allograft

Cited by 31 publications

References 36 publications

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor-Specific Antibody Characteristics

Spleen Tyrosine Kinase Modulates Fibrous Airway Obliteration and Associated Lymphoid Neogenesis After Transplantation

Practical Applications in Immunohistochemistry: Evaluation of Rejection and Infection in Organ Transplantation

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