engleski

Oral Candida species colonization in chronic Graft-versus-Host Disease

Introduction: Colonization with Candida sp has significant role in occurrence and pathogenesis of acute Graft-versus-Host Disease (aGVHD) via induction of mucosal innate immunity (Th 17/IL 23 responses). However, data about prevalence and role of Candida sp in chronic Graft-versus- Host Disease (cGVHD) are scarce. The aim of this study was to determine prevalence of oral colonization with different Candida sp in patients with cGVHD and possible association with cGVHD characteristics. Materials (or patients) and methods: This study enrolled cGVHD patients who are part of a larger multidisciplinary cGHVD project at the University Hospital Center Zagreb, Croatia. Patients were evaluated for clinical and cGVHD characteristics ; severity of cGVHD and oral involvement were determined by using established NIH Consensus criteria. Swabs from oral cavity were collected from all patients. Specimens were analyzed by standard cultivation methods (Sabouraud and blood agar, identification by automated biochemical test). Molecular detection was performed by real-time in house PCR designed to distinguish 12 Candida species. Candida isolates were analyzed at proteomic level by Mass Spectrometry (MS/MS). Data were evaluated descriptively. Fisher’s exact test or Wilcoxon test were used to calculate statistical significance. Results: Twenty-one patient was enrolled, median age was 42 years 38% were male. In 15 patients (71%) underlying disease was AML, ALL or MDS, 3 patients had CML or MPN, 1 patient had severe aplastic anemia and 2 patients had lymphoma. Nine patients (43%) underwent myeloablative conditioning. Majority (71%) received PSBC as stem source. Sixteen patients (76%) had previous aGVHD. Ten patients (48%) had oral cGVHD ; 6 patients had moderate or severe NIH oral cGVHD score. Nine patients (43%) had moderate and 12 (57%) had severe NIH global cGVHD score. Six patients (29%) were positive for C. albicans and 3 patients for C. krusei by standard cultivating methods. When using real- time PCR method, 13 patients (61%) were positive for C. albicans, 4 patients for C. krusei, 2 patients with C. dubliensis, 1 patient with C. tropicalis and 1 patient with C. glabrata. Coinfection with 2 or 3 different Candida sp. was found in 6 patients. Ten samples were analyzed by proteomics with 5 samples confirmed as C. albicans. Although more patients were positive for C. albicans and C. non albicans sp by multiplex PCR than cultivation, this was not statistically significant (P¼0.335 and 0.184, respectively). Nine patients with oral cGVHD (90%) had colonization with at least one Candida sp, while 7 patients without oral cGVHD (64%) had colonization with Candida sp (P¼0.311). Ten patients with global severe cGVHD (83%) and 5 patients with moderate cGVHD (55.5%) had Candida sp colonization (P¼0.331). Conclusion: Significant proportion of patients with cGVHD, especially patients with severe global cGVHD were colonized with Candida sp. Use of molecular methods is important in diagnosing C.non albicans (3 new species identified only by PCR). Majority (90%) of patients with oral cGVHD were colonized with Candida sp, however larger studies are needed to determine association between cGVHD global severity and organ involvement with Candida colonization. Considering significant proportion of cGVHD patients colonized with Candida sp, further studies investigating its possible role in pathogenesis of cGVHD, as well as possible prophylactic/therapeutic are needed. Disclosure of Interest: None declared.

cGVHD ; Candida

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