Association of cytomegalovirus interstitial pneumonitis with HLA-type following allogeneic bone marrow transplantation

Abstract

Summary:Certain human leukocyte antigens may increase the risk of cytomegalovirus interstitial pneumonitis, an important complication of bone marrow transplantation. The prevalence of this pneumonitis was compared between patients possessing either HLA-B51 or HLA-B52 and patients without either antigen. The role of tumor necrosis factor-␣ in cytomegalovirus interstitial pneumonitis was also studied. Among 72 patients undergoing allogeneic bone marrow transplantation at our institution during the past 5 years, HLA-B51 or -B52 was detected in 29. Among these 29 patients, 13 (45%) developed cytomegalovirus interstitial pneumonitis, a significantly higher rate (P Ͻ 0.001) than among patients without these HLA types (4/43, 9%). In the preconditioning and stable phases, tumor necrosis factor-␣ levels were higher in patients with HLA-B51 or HLA-B52 than in patients without (P Ͻ 0.05; t-test). Throughout the period from pre-conditioning to around day 40, except on day 0, tumor necrosis factor-␣ levels were also significantly higher (P Ͻ 0.05 to P Ͻ 0.001) in patients developing cytomegalovirus infection than in those without it. These results suggest that HLA-B51 and HLA-B52 may be risk factors for cytomegalovirus interstitial pneumonitis after bone marrow transplantation, with an increase of tumor necrosis factor-␣ also being involved. Bone Marrow Transplantation (2000) 25, 861-865. Keywords: cytomegalovirus interstitial pneumonitis; human leukocyte antigen; bone marrow transplantation; tumor necrosis factor-␣ Cytomegalovirus interstitial pneumonitis (CMV-IP) is a very important and common complication of bone marrow transplantation (BMT), which can influence the outcome of this procedure. There have been many reports on the risk factors, preventive measures, and treatment of CMV-IP. [1][2][3][4] We focused on the influence of human leukocyte antigen (HLA) status, investigating HLA-B51 and HLA-B52, for which an association with CMV-IP has not yet been reported. The frequency of HLA-B51 is significantly increased in patients with Behçet's disease, 5 and the same is true for HLA-B52. 6 Neutrophil dysfunction, 5,7 immunological abnormalities, 7,8 and microvascular inflammation, 9,10 caused by an increase of tumor necrosis factor (TNF)-␣ are generally accepted to occur in Behçet's disease. In the present study, the influence of HLA-B51 and HLA-B52 was assessed in patients with CMV-IP diagnosed at our institution over the past 5 years since the establishment of preventative therapy for this disease. In addition, changes of the TNF-␣ level were studied in an attempt to clarify the role of this cytokine in CMV-IP. Materials and methods PatientsThe subjects were 72 consecutive patients who were seropositive for CMV or whose donors were seropositive and who underwent allogeneic BMT at our department between April 1994 and March 1999. Before bone marrow transplantation, all patients were in good condition without any signs of infection. HLA typingA serological method was used for HLA typing. Two controls were provided for each o...

Oral eicosapentaenoic acid for complications of bone marrow transplantation

“…We have previously shown that certain cytokines, chemokines, and adhesion molecules participate in the development of endothelial damage in each of these complications. [10][11][12][13][14][15] In addition, we have reported that these various complications can all be considered as manifestations of the systemic inflammatory response syndrome (SIRS). 1 In this syndrome, dysfunction of multiple organs is caused by vascular endothelial damage arising from increased production of inflammatory cytokines induced by certain stimuli or inflammation.…”

“…Among the various complications of BMT, it is known that GVHD, 10,11 thrombotic microangiopathy, 12 CMV disease, 13 respiratory dysfunction resembling adult respiratory disease syndrome, 14 and central nervous system dysfunction 15 are accompanied by vascular endothelial dysfunction. We have previously shown that certain cytokines, chemokines, and adhesion molecules participate in the development of endothelial damage in each of these complications.…”

Vascular endothelial growth factor (VEGF) is associated with reduced severity of acute graft-versus-host disease and nonrelapse mortality after allogeneic stem cell transplantation

“…28 The interactions between VEGF and then transplant-related complications including CDI, hepatic VOD, TM, CMV infection and GVHD were examined according to the VEGF cluster. The incidence of complications except for the occurrence of acute GVHDXIII was similar in the two VEGF groups (Table 2), which means that VEGF may play a major role Table 3 Univariate Cox regression analysis of the risk factors associated with nonrelapse mortality…”

Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome

“…[1][2][3][4][5] Control of these complications is complex and difficult, and it is not unusual for there to be an unfavorable outcome. We have previously demonstrated that vascular endothelial damage and hypercytokinemia are involved in central nervous system disorders, 6 adult respiratory distress syndrome (ARDS)-like respiratory disorders, 7 thrombotic microangiopathy (TMA), 8 acute graft-versus-host disease (GVHD), 9 and cytomegalovirus (CMV) infection 10 among the complications occurring after BMT. In this study, we attempted to unify the various complications occurring after BMT by considering them as manifestations of systemic inflammatory response syndrome (SIRS).…”