ISSN 1866-8836
Клеточная терапия и трансплантация

PC-06. Zonulin and calprotectin as markers of posttransplantation complications after allogeneic hematopoietic stem cell transplantation

Anastasia I. Reshetova, Dmitry V. Motorin, Darina B. Zammoeva, Renat Sh. Badaev, Alexey S. Golovkin

Almazov National Medical Research Center, St. Petersburg, Russia; World-class Research Center for Personalized Medicine, St. Petersburg, Russia; Research Institute of Hematology and Transfusiology, St. Petersburg, Russia


Contact: Dr. Anastasia I. Reshetova, phone: +7 (923) 508-44-94, e-mail: makena1@inbox.ru

doi 10.18620/ctt-1866-8836-2023-12-3-1-176

Summary

Efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with oncohematological diseases largely depends on the complications of the posttransplantation period. Damage to the gastrointestinal tract and impaired barrier function may affect the pathogenesis of complications. Our objective was to study the prognostic role of calprotectin and zonulin in genesis of allo-HSCT complications.

Materials and methods

The study included 26 patients 18 to 60 years old subjected to allo-HSCT aimed for treatment of oncohematological disorders. Stool specimens were taken of the patients 7 days before HSCT, and on days +14, +30, +60 and +90 days. After sampling, the biological material was immediately frozen and stored at -80ºC. Fecal calptotectin was quantified by means of lateral immune chromatography; zonulin was assayed by ELISA technique. The results are presented as median values and interquartile ranges. Significance of the differences was evaluated by the Mann-Whitney criterion.

Results

Graft-versus-host disease (GvHD) II-IV degree developed in 53% of the patients subjected to allo-HSCT. On day +30 after allo-HSCT, the level of calprotectin in this group was higher than in the cases of grade 0-I GvHD [109 (32; 163), and 31 (25; 53) µg/mL, respectively, p=0.03] as well as on day +60 [112 (31;126), and 26 (25;44) µg/mL, respectively, p=0.02]. Zonulin levels tended to increase in severe GvHD compared with patients without GvHD on day +30 [(112 (42;183), and 80 (12;104) ng/mL, p=0.2] as well as on day +60 [100 (12;180), and 33 (8;107) ng/mL, respectively, p=0.4], and on day +90 [182 (9;192), and 29 (16;41) ng/mL, p=0.2]. When comparing skin and intestinal lesions, the level of calprotectin was higher in the second case on day +30 [25 (31; 72), and 87 (58;181) mcg/ml, p=0.04], the levels of zonulin did ot differ significantly. In 53.8% of patients, the posttransplantation period was complicated by grade 2-4 mucositis. The level of calprotectin before HSCT was higher in patients with mild (0-1) grade mucositis compared with severe mucositis [80 (59;205) and 32 (26;38) mcg/ml, p=0.02]. On the 14th and 30th day, no significant differences were revealed. Zonulin levels were elevated to allo-HSCT in mild mucositis [196 (173;218), and 125 (49;151) ng/ml, respectively, p=0.047], but did not significantly differ in subsequent period. In the group of patients who survived for more than 12 months compared to lethal cases, low levels of calprotectin [38 (26;87) and 146 (65; 109) mcg/ml, p=0.01] and zonulin [32 (10;131) and 182 (81;250) ng/ml, p=0.04] on the 30th day after transplantation.

Discussion

The majority of patients who underwent allo-HSCT initially had elevated levels of zonulin and calprotectin relative to the reference normal values. This finding may indicate an impairment of intestinal barrier even before the transplantation. In addition, lower values of both calprotectin and zonulin in the group of patients with further severe mucositis, were noted before transplantation. Upon development of severe GvHD, the level of calprotectin was significantly increased during GvHD with intestinal damage.

Conclusion

Our preliminary results indicate that the levels of calprotectin and zonulin in faeces may be considered prognostic markers of the development of severe mucositis, GvHD and mortality in the patients after allo-HSCT.

Keywords

Calprotectin, zonulin, allogeneic hematopoietic stem cell transplantation, complications, graft-versus-host disease.


Supplement 12-3
09/30/2023

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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