Acquired immunodeficiency in patients with hematological oncology is a serious and common complication, significantly impacting prognosis and quality of life. High doses of cytostatic drugs and the malignancy itself lead to suppression of the immune system, leaving the body vulnerable to various infectious agents. Sepsis, which develops in the setting of immunodeficiency, is characterized by a more aggressive course and high mortality. In the era of advancing sequencing technologies, identifying polymorphisms and changes in innate immune gene expression associated with the development and severity of sepsis, as well as their impact on outcome, is crucial.
We analyzed DNA samples (n = 155) from oncohematology patients with severe sepsis in the Department of Anesthesiology and Intensive Care at the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. The presence/absence of the rs1024611 polymorphism in the promoter region of the MCP-1 gene was determined using Sanger sequencing.
The presence of homo- or heterozygous polymorphism was found to be associated with an increased risk of developing septic shock (χ2 = 4.9, p = 0.013). This supports the hypothesis that genetic factors influencing MCP-1 levels may be associated with a more pronounced systemic inflammatory response, leading to more severe clinical outcomes. In patients with the rs1024611 polymorphism, the likelihood of developing sepsis-associated acute kidney injury requiring renal replacement therapy (RRT) was higher (χ2 = 13.0, p = 0.00016) compared to patients without RRT. Patients with the rs1024611 polymorphism also have an increased risk of developing severe acute respiratory distress syndrome (ARDS) (χ2 = 4.8, p = 0.014). Furthermore, the presence of homo- or heterozygous rs1024611 polymorphism increases the likelihood of an adverse outcome, such as 28-day mortality (χ2 = 5.6, p = 0.009). This underscores the importance of genetic factors in determining the prognosis of patients with sepsis. High mortality may be associated with a more pronounced inflammatory response caused by the polymorphism, leading to more severe forms of sepsis and its complications.
The rs1024611 polymorphism in the MCP-1 gene promoter region is significantly associated with an increased risk of severe sepsis secondary to secondary immunodeficiency. These data highlight the importance of genetic testing for risk assessment and prognosis in patients with sepsis.
