A New Approach to Predict the Chance of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation: Mannose-Binding Lectin ELISA

Abstract

Abstract 4492 Introduction:Haematopoietic stem cell transplantation associated immuncompromised state carries high risk of infectious complications. Gram-positive cocci are responsible for the majority of the post-transplant bloodstream infections. Viral and invasive fungal infections can be significant causes of morbidity.Mannose-binding lectin (MBL) is involved in innate immune response. MBL is an acute phase protein, synthesized in the liver. MBL binds microbial surface carbohydrates and mediates opsonophagocytosis directly and by activation of the lectin complement pathway. MBL also functions as co-receptor of Toll-like receptor. Serum MBL level is genetically determined and quite stable. MBL deficiency is a result of impaired assembly or stability of multimers.In patients who received high dose chemotherapy/transplantation, the innate immunodeficiency is an additive risk factor for infectious complications.According to literature, significant association was shown between low concentrations of MBL and serious infections. MBL is a potential modifier of susceptibility to infection in patients who have chemotherapy-induced neutropenia. Furthermore, infections might also compromise the engraftment of stem cells and the development of cell-lines might be prolonged. Patients and methods:The association between serum MBL level and frequency, severity and occurrence of infections has been studied in 127 patients following autologous stem cell transplantation (ASCT). Subgroups, i.e. multiple myeloma, non-Hodgkin and Hodgkin lymphoma were formed and the infectious complications have been compared.A double-monoclonal antibody sandwich ELISA system (BioPorto, Denmark) was used, which is a sensitive method for determining the MBL antigen levels in the sera.The range of MBL level in healthy population varies between 5 and 5000 ng/ml, <100 ng/ml is defined as MBL deficiency. MBL antigen levels were measured following transplantation, in a period without the presence of active infection. Results:18 patients (out of 127) proved to be MBL deficient. The median time of the onset of first infection was day +5 in MBL deficient, while day +15 among non-MBL deficient patients following transplantation. More infections were found among MBL deficient patients (2.44 vs 2.28 infectious episodes/patient). When patients with more and less than 500 ng/ml serum MBL level were compared, similar trends were seen, but the difference was not significant.The occurrence of absolute MBL deficiency was not different between patients with malignant hematological diseases and the 294 healthy controls (14.5% vs 14%). Interestingly, MBL serum levels were significantly higher in the examined patients with malignant hematological diseases compared to healthy controls. Conclusions:MBL deficiency may predispose to infections. To our best knowledge, this is one of the first reports regarding MBL deficiency in bone marrow transplant settings. Our MBL deficient patients had a greater number of severe infections and experienced their first severe infection earlier, compared to nondeficient patients following ASCT. The measuring of MBL may be helpful in antibiotic treatment, in case of MBL deficiency earlier and more intensive treatment may be indicated.Table 1The distribution of infections by MBL levelsTotalMBL <100 ng/mlMBL >100 ng/mlnumber of patients12718109patients with infections11916103infected/total (%)93.788.8994.5number of infectious episodes29244248infectious episodes/ one patient2.32.442.28development of first infection (day, mean)13.75.315mean follow-up325.9311.5328.3bloodstream-infection26 (8.9%)3 (6.8%)23 (9.3%)fever, high CRP, severe mucositis70 (24%)12 (27.3%)58 (23.4%)respiratory tract infection72 (24.7%)16 (36.3%)56 (22.6%)viral infection22 (7.5%)2 (4.5%)20 (8.1%)oral mycosis13 (4.5%)1 (2.3%)12 (4.8%)GI tract disease39 (13.4%)7 (16%)32 (13%)elevated CRP32 (11%)2 (4.5%)30 (12%)other17 (5.8%)1 (2.3%)16 (6.5%) Disclosures:No relevant conflicts of interest to declare.