Immunological diversity in phenotypes of chronic lung allograft dysfunction: a comprehensive immunohistochemical analysis

Abstract

SUMMARYChronic rejection after organ transplantation is defined as a humoral-and cell-mediated immune response directed against the allograft. In lung transplantation, chronic rejection is nowadays clinically defined as a cause of chronic lung allograft dysfunction (CLAD), consisting of different clinical phenotypes including restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). However, the differential role of humoral and cellular immunity is not investigated up to now. Explant lungs of patients with end-stage BOS (n = 19) and RAS (n = 18) were assessed for the presence of lymphoid (B and T cells) and myeloid cells (dendritic cells, eosinophils, mast cells, neutrophils, and macrophages) and compared to nontransplant control lung biopsies (n = 21). All myeloid cells, with exception of dendritic cells, were increased in RAS versus control (neutrophils, eosinophils, and mast cells: all P < 0.05, macrophages: P < 0.001). Regarding lymphoid cells, B cells and cytotoxic T cells were increased remarkably in RAS versus control (P < 0.001) and in BOS versus control (P < 0.01). Interestingly, lymphoid follicles were restricted to RAS (P < 0.001 versus control and P < 0.05 versus BOS). Our data suggest an immunological diversity between BOS and RAS, with a more pronounced involvement of the B-cell response in RAS characterized by a structural organization of lymphoid follicles. This may impact future therapeutic approaches.

Advanced Role of Neutrophils in Common Respiratory Diseases

“…Clinical research showed us that the percentage of lymphocytes and neutrophils increased and the percentage of macrophages reduced in BALF of patients with OB [228]. This is similar with the reports, which suggest an involvement of neutrophils in OB from both Vandermeulen et al and Eckrich et al [229, 230]. Tiriveedhi et al reported that neutrophil can participate in the obliterative airway disease and cause the early injury after passive transfer of CD8+ T cells [231].…”

Chronic lung allograft dysfunction phenotypes and treatment

“…Other studies focused on particular (inflammatory) cytokines and chemokines. lymphoid follicles, which is a common finding in other chronic respiratory diseases (62). Given this presence of lymphoid follicles, it comes as no surprise that immunoglobulin levels were also increased in rCLAD (63).…”

Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series

“…[1][2][3][4] RAS is characterized by restrictive pulmonary physiology and persistent pleuroparenchymal abnormalities, such as peripheral ground-glass opacities, consolidation, traction bronchiectasis, architectural distortion, and (sub)pleural thickening on chest computed tomography (CT) scan. 12,13 Importantly, RAS carries an unfavorable prognosis with a median survival of 1-1.5 years after disease onset. 12,13 Importantly, RAS carries an unfavorable prognosis with a median survival of 1-1.5 years after disease onset.…”

“…Notably, 3 patients were bridged to redo-transplantation with pirfenidone for 11 (5)(6)(7)(8)(9)(10)(11)(12) months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function after 26.6 (range 18.4-46.6) months of treatment. We retrospectively assessed all lung transplant recipients with RAS who were treated with pirfenidone for at least 3 months (n = 11) in our lung transplant center and report on their long-term outcomes following initiation of pirfenidone.…”