Humorally mediated posttransplantation septal capillary injury syndrome as a common form of pulmonary allograft rejection: a hypothesis

Abstract

Septal capillary injury accompanied by direct and indirect immunofluorescent evidence of humoral immunity is a frequent finding on transbronchial biopsies. The findings suggest that humoral immunity to endothelial-based alloantigen is a common occurrence in lung grafts and may be a critical factor in chronic graft dysfunction.

Evidence That Humoral Allograft Rejection in Lung Transplant Patients Is Not Histocompatibility Antigen-Related

“…We have recently shown a role for humoral immunity in the propagation of acute and chronic lung graft dysfunction (1). Features of the acute syndromic complex are those of dyspnea, fever, and lung infiltrates, while light microscopically there is evidence of a necrotizing septal capillary injury syndrome accompanied by immunoreactant deposition within the interalveolar septal capillaries (1).…”

“…Features of the acute syndromic complex are those of dyspnea, fever, and lung infiltrates, while light microscopically there is evidence of a necrotizing septal capillary injury syndrome accompanied by immunoreactant deposition within the interalveolar septal capillaries (1). In patients fulfilling the criteria for bronchiolitis obliterans syndrome (BOS), the prototypic cause of chronic lung graft dysfunction, bronchial wall immunoreactant deposition with localization to the bronchial epithelium and microvasculature of the bronchial wall has also been recently identified (2).…”

The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens

“…4,9,10 However, it is important to note that the use of C4d as a surrogate marker for development of DSAs and subsequent AMR in lung has shown conflicting results. [11][12][13][14][15][16][17][18][19][20] Some studies have shown a correlation between the presence of DSAs and C4d deposition in lung allografts but others have not. 11,17,20 It is critical to correctly identify patients with AMR because the development of anti-HLA alloantibody has been shown to be a major risk factor for poor outcomes in lung transplants.…”

“…[11][12][13][14][15][16][17][18][19][20] Some studies have shown a correlation between the presence of DSAs and C4d deposition in lung allografts but others have not. 11,17,20 It is critical to correctly identify patients with AMR because the development of anti-HLA alloantibody has been shown to be a major risk factor for poor outcomes in lung transplants. 21,22 Additionally, the development of anti-HLA DSAs is associated with high-grade acute cellular rejection (ACR), lymphocytic bronchiolitis, bronchiolitis obliterans syndrome, and increased use of immunosuppressive therapy.…”

“…However, all of these findings are rather nonspecific, and consistency between studies is less than desired. 11,19,20,24 Ideally, DSA positivity correlated with C4d deposition, histologic findings, and clinical status of lung allograft recipients could help in the diagnosis of AMR and ultimately dictate optimal patient care. The goal of this study was to identify lung allograft recipients who developed DSAs and to compare corresponding biopsy specimens for C4d immunofluorescence in order to determine if it is a reliable marker for AMR.…”