Background: Oral and enteral mucositis due to high-dose cytostatic treatment administered during autologous and allogeneic stem-cell transplantation increases mortality. Salivary secretory immunoglobulin A (sIgA) is a basic pillar of local immunity in the first line of defense. Altered salivary sialoglycoprotein carbohydrates are important in the pathologies in the oral cavity including inflammation, infection and neoplasia. Therefore, we assessed whether changes in the salivary and serum IgA glycosylation correlated with development and severity of oral mucositis. Methods: Using capillary electrophoresis, comparative analysis of serum and salivary IgA total N-glycans was conducted in 8 patients with autologous peripheral stem-cell transplantation (APSCT) at four different stages of transplantation (day −3/−7, 0, +7, +14) and in 10 healthy controls. Results: Fourteen out of the 31 structures identified in serum and 6 out of 38 in saliva showed significant changes upon transplantation compared with the control group. Only serum core fucosylated, sialylated bisecting biantennary glycan (FA2BG2S2) showed significant differences between any two stages of transplantation (day −3/−7 and day +14; p = 0.0279). Conclusion: Our results suggest that changes in the serum IgA total N-glycan profile could serve as a disease-specific biomarker in patients undergoing APSCT, while analysis of salivary IgA N-glycan reflects the effect of APSCT on local immunity.
Oral mucositis (OM) is a frequent complication of stem cell transplantation-associated toxicity in haematological malignancies, contributing to mortality. Therapy still remains mainly supportive. We assessed risk factors in retrospective analysis of 192 autologous peripheral stem cell transplantation patients with lymphoma and multiple myeloma (MM), respectively. Futhermore, we examined the hormone levels both in serum and saliva during transplantation in 7 postmenopausal female patients with lymphoma compared to healthy controls using electrochemiluminescence immunoassay (ECLIA). Multivariable analysis revealed neutrophil engraftment (p < 0.001; p = 0.021) and female sex (p = 0.023; p = 0.038) as independent predictive factors in the combined patient group and in the lymphoma group, and neutrophil engraftment (p = 0.008) in the MM group. Of the 85 female participants 19 were pre- and 66 postmenopausal. Fifteen of the pre-, and 49 of the postmenopausal women developed ulcerative mucositis (p = 0.769), more often with lymphoma than MM (p = 0.009). Serum estrogen decreased significantly both in postmenopausal controls and transplantated patients compared to premenopausals, with no difference in saliva. Serum progesterone level was significantly (p = 0.026) elevated at day + 7 of transplantation, while salivary progesterone increased at day + 7 and + 14. Our results indicate a predominantly negative effect of female sex hormones on oral immunity with role in the aetiopathogenesis of OM.
Aims: To apply capillary electrophoresis with laser induced fluorescence detection (CE-LIF) to identify the N-glycosylation structures of serum and saliva IgA from healthy controls and patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions. Background: Altered N-glycosylation of body fluid glycoproteins can be effective indicators of most inflammatory processes. Immunoglobulin A (IgA) is the second highest abundant of the immunoglobulins and has a major role in the immune-defense against potential pathogen attacks. While IgA is abundant in serum, secretory immunoglobulin A (sIgA) is one of the most prevalent proteins in mucosal surfaces such as in saliva. Objective: Our aim was to investigate the changes of IgA glycosylation in serum and saliva as a response to an administered cytostatic treatment in patients with malignant hematological disorders. Materials: Capillary electrophoresis with laser induced fluorescent detection (CE-LIF) was used to analyze the N-glycosylation profiles of Z(IgA1) partitioned immunoglobulin A in pooled serum and saliva of 10 control subjects and 8 patients with malignant hematological diseases having cytostatic treatment induced mild oral mucosal lesions. Results: Eight of 31 and four of 38 N-glycans in serum and saliva, respectively, showed significant (p<0.05) differences upon comparison to the control group. Thirteen glycans were present in the saliva but not in the serum, on the other hand six structures were found in the serum samples not present in the saliva. Conclusion: The developed Z(IgA1) partitioning and the high resolution CE-LIF based glyocoanalytical methods provided an efficient and sensitive workflow to detect and monitor IgA glycosylation alterations in serum and saliva with the scope for widespread molecular medicinal use.
Osteopontin (OPN), a multifunctional phosphoglycoprotein also presents in saliva, plays a crucial role in tumour progression, inflammation and mucosal protection. Mucosal barrier injury due to high-dose conditioning regimen administered during autologous and allogeneic peripheral stem cell transplantation (APSCT) has neither efficient therapy nor established biomarkers. Our aim was to assess the biomarker role of OPN during APSCT, with primary focus on oral mucositis (OM). Serum and salivary OPN levels were determined by ELISA in 10 patients during APSCT at four stages of transplantation (day −3/−7, 0, +7, +14), and in 23 respective healthy controls. Results: There was a negative correlation between both salivary and serum OPN levels and grade of OM severity during APSCT (r = −0.791, p = 0.019; r = −0.973, p = 0.001). Salivary OPN increased at days +7 (p = 0.011) and +14 (p = 0.034) compared to controls. Among patients, it was higher at day +14 compared to the time of admission (day −3/−7) (p = 0.039) and transplantation (day 0) (p = 0.011). Serum OPN remained elevated at all four stages of transplantation compared to controls (p = 0.013, p = 0.02, p = 0.011, p = 0.028). During APSCT elevated salivary OPN is a potential non-invasive biomarker of oral mucositis whereas the importance of high serum OPN warrants further studies.
Morphological transitions of wild-type and oxidative stress-tolerant Candida albicans strains were followed in the RPMI-FBS culture medium at pH values and CO 2 levels characteristic for the anatomical niches inhabited by this opportunistic human pathogen fungus, including the oral cavity as well as the intestinal and vaginal lumens. Selected cultures were also supplemented with hemin modeling bleedings. Germination as well as elongation and branching of hyphae were monitored in the cultures using time-lapse video microscopy. Unexpectedly, branching time, which is defined as the time taken until the first branch of hypha emerges for the first time after germination, correlated well with alterations in the environmental conditions meanwhile no such correlations were found for germination time (time lasted until the *Corresponding author; E-mail: pocsi.istvan@science.unideb.hu : 10.1556/030.63.2016.023 First published online December 8, 2016 1217-8950/$ 20.00 © 2016 Akadémiai Kiadó, Budapest appearance of the germination tube). Based on these observations, hypotheses were set up to estimate the significance of branching time in the pathogenesis of both superficial and systemic candidiases.Acta Microbiologica et Immunologica Hungarica 63 (4), pp. 387-403 (2016) DOI
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