The search continues for pathogenetically effective measures in autoimmune processes for a number of complications of type 1 diabetes mellitus, in particular, diabetic retinopathy. However, there are few studies of the prognostic and therapeutic values of the systemic autoimmune response in this pathology after transplant of autologous mesenchymal stem cells. Here, we present a 40-year-old patient with complications of type 1 diabetes mellitus (diabetic retinopathy) after mesenchymal stem cell transplant. Based on peripheral blood results, we were able to calculate integral hematologic parameters, allowing us to indirectly assess the patient’s immune system after autologous mesenchymal stem cell transplant. One month after autologous mesenchymal stem cell transplant, we observed a positive immune response, with a 40% decrease in leukocyte intoxication index and a 22% increase from the initial lymphocyte and eosinophil ratio index values, which indicated the formation of a delayed-type hypersensitivity reaction. Two months after transplant, stem cell leukocyte intoxication index, in contrast, increased by 10%, indicating a possible metabolic shift. At the same time, changes were observed in the lymphocyte stimulation index value, which increased by 11%. This observation indicated negative immunologic reactivity, namely, poor function of factors of nonspecific resistance due to autointoxication of the organism. However, 3 months after transplant, the hematologic parameters of this patient returned to levels before treatment. The use of integral hematologic parameters can indirectly interpret parallels between immunologic reactivity and metabolic disorders in type 1 diabetes mellitus complications (diabetic retinopathy) after autologous mesenchymal stem cell transplant. These parameters could become a diagnostic indicator in the correction of pathogenetic therapy.
Key words : Immune system, Leukocyte intoxication index, Lymphocyte stimulation index
Autologous cell groups (that is, the patient’s own cells) have the greatest chance of functioning in the body due to the absence of rejection by its immune system.1 In patient’s with diabetes mellitus, immuno-logic reactivity can launch a cascade of consecutive interconnected stages of development of vascular retinal pathology in response to patient hypoxia.2,3 Hence, searches have continued for pathogenetically effective diagnostic and therapeutic measures in autoimmune processes for complications of type 1 diabetes mellitus, particularly diabetic retinopathy, are relevant. However, studies of the systemic auto-immune response in this pathology after autologous mesenchymal stem cell (MSC) transplant with regard to prognostic and therapeutic values are rare.
In this case report, we present a 40-year-old patient with complications of type 1 diabetes mellitus (diabetic retinopathy) after MSC transplant. Autologous MSCs were obtained from bone marrow samples of the iliac crest of the patient and cultured for 3 to 4 weeks. Autologous MSC transplant was performed using intravenous infusion at a rate of 50 mL/hour. The quantity of autologous MSCs infused was 95 to 97 × 106. This clinical study and its methods were approved by the Local Ethics Committee following Helsinki Declaration guide-lines at our institution. The patient provided written informed consent before recruitment.
Statistical analyses were performed using standard methods and Stastistica software (StatSoft Inc., version 6.0, Tulsa, OK, USA).
To assess the contribution of autologous MSCs to the development of changes in the patient’s immunological parameters, we calculated 5 integral hematologic parameters of peripheral blood (Table 1). These included (1) the modified leukocyte index of intoxication (LII), an indicator of the processes of tissue degradation and the level of endogenous intoxication; (2) the ratio of neutrophils to lymphocytes; (3) the ratio of neutrophils to monocytes, which makes it possible to judge the ratio of the components of the phagocytic system, and the ratio of lymphocytes to monocytes; (4) the ratio of lymphocytes to eosinophils, which has already been used to characterize the processes of hypersensitivity of the immediate and delayed types; and (5) the leukocyte index, which reflects the relationship of cellular and humoral immunity.4-6 These calculations allowed us to indirectly assess the state of the immune system in patients after autologous MSC transplant.
Here, we used integral hematologic indicators to determine the state of immunologic reactivity of the organism against the introduction of autologous MSCs in a patient with type 1 diabetes mellitus and diabetic retinopathy. Although this is a small clinical laboratory research report, our observations were somewhat encouraging and the data were statistically confirmed. Thus, the use of integral hematological parameters could indirectly interpret parallels between the state of immunologic reactivity of an organism and metabolic disorders, as in complications of type 1 diabetes mellitus (diabetic retinopathy) after autologous MSC transplant. Results of calculations could be used as diagnostic indicators in the correction of pathogenetic therapy.
Volume : 17
Issue : 1
Pages : 234 - 235
DOI : 10.6002/ect.MESOT2018.P99
From the 1Department of Ophthalmology, the 2Department of Endocrinology, the
3Department of Stem Cell Technology, the 4Department of Clinical Laboratory, the
National Scientific Medical Research Center; and the 5Laboratory of Clinical
Immunology, Research Institute of Traumatology and Orthopedics, Astana,
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Manshuk Yeltokova, Department of Ophthalmology, National Scientific Medical Research Center, 010009, Ave. Abylay-khan #42, Astana, Kazakhstan
Phone: +7 70 15 202484
Table 1. Integral Hematologic Results in a Patient With Type 1 Diabetes Mellitus and Diabetic Retinopathy Before and After Autologous Mesenchymal Stem Cell Transplant