Associations of Ficolins With Hematological Malignancies in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantations

Abstract

A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between "self" "abnormal self," and "non-self" and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation via the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the corresponding (FCN1, FCN2, and FCN3) genes. Serum samples were collected before conditioning chemotherapy, before HSCT, and once weekly post-HSCT (four to five samples in total); some patients were also sampled at 1 and/or 3 months posttransplantation. The control group (C) consisted of 267 healthy unrelated individuals. Median ficolin-1 and ficolin-2 (but not ficolin-3) levels in MM patients' sera taken before chemotherapy were lower (and correspondingly frequencies of the lowest concentrations were higher) compared with controls. That appeared to be associated with the malignant disease itself rather than with post-HSCT complications (febrile neutropenia, infections accompanied, or not with bacteremia). Higher frequencies of the FCN1 genotype G/A-C/C-G/G (corresponding to polymorphisms at positions −542, −144, and +6658, respectively) and FCN2 gene heterozygosity for the −857 C>A polymorphism were found among patients diagnosed with MM compared with the C group. Furthermore, Ś wierzko et al. Ficolins in Hematological CancersFCN2 G/G homozygosity (−557 A>G) was found more frequently and heterozygosity G/T at +6424 less frequently among LYMPH patients than among the healthy subjects. Heterozygosity for +1637delC mutation of the FCN3 gene was more common among patients diagnosed with lymphomas who experienced hospital infections. Although no evidence for an association of low ficolin-1 or ficolin-2 with infections during neutropenia following chemotherapy before HSCT was found, we observed a possible protective effect of ficolins during follow-up.

Associations of ficolins and mannose-binding lectin with acute myeloid leukaemia in adults

“…Another SNP, located in exon 9 (+ 7,959 A > G; N299S; rs138055828) and two located in the promoter region (− 542 G > A, rs10120023 and − 144 C > A, rs10117466) were tested with PCR-RFLP as well, using in-house procedures 27 . Briefly, PCRs were run on a C1000 Thermal Cycler (Bio-Rad, Hercules, CA, USA), using appropriate spanning primers, designed with the use of PRIMER3 software (version 0.3.0), https ://bioin fo.ut.ee/prime r3/ 62,63 (Table 5).…”

“…"Low" and "high" values were arbitrarily based on 10th and 95th percentiles respectively, determined for the control group. Consequently, concentrations < 620 ng/ml (ficolin-1), < 1,670 ng/ml (ficolin-2) and < 12.9 µg/ml (ficolin-3) were considered "low" while > 2.9 µg/ml, > 6.35 µg/ml and > 34.9 µg/ml, respectively were considered "high" 27 . Exceptionally, MBL was considered "low" when its concentration was < 150 ng/ml (as MBL deficiency) while "high" MBL consequently corresponded to the 95th percentile for the control group (> 3 µg/ml) 37 .…”

“…The ROC analysis demonstrated high potential of ficolin-1 to discriminate not only between AML patients and healthy controls but also between AML patients and individuals suffering from other haematological malignancies [multiple myeloma or lymphomas; detailed data concerning serum concentrations of ficolins in those patients were recently published 27 (Table 4). Such a significant association was not reported earlier, although ficolin-1 was suggested to be candidate for marker of other cancers: colorectal cancer and adenoma 28 .…”

Components of the Lectin Pathway of Complement in Haematologic Malignancies

“…Our recent investigations [ 98 , 118 ] revealed markedly lower ficolin-1 concentrations in patients suffering from multiple myeloma or acute myeloid leukaemia (before chemotherapy), compared with controls. The median in the AML group was almost fivefold lower than in healthy controls (260 ng/mL vs. 1277 ng/mL).…”

The Influence of the Lectin Pathway of Complement Activation on Infections of the Respiratory System

“…Furthermore, ficolin-2 binds to the surface structures of opportunistic Pasteurella pneumotropica [reviewed in (19)] ( Table 1). Although the serum concentration of ficolin-3 (H-ficolin, Hakata antigen) was found to be the highest among PRM specific for the lectin pathway [its median level in healthy adults is 20 µg/ml or above (23)(24)(25)], few microbial targets have been reported. However, among those few are several respiratory pathogens: A. fumigatus, M. tuberculosis, IAV, and the afore-mentioned Pasteurella pneumotropica [reviewed in (19)] ( Table 1).…”