Regulatory effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin on inflammation and immune function in percutaneous nephrolithotomy patients with upper urinary tract calculi complicated with infection

Abstract

ObjectiveTo study the effect of an injection of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on inflammation and immune function in patients with upper urinary tract calculi complicated by infection who have undergone percutaneous nephrolithotomy.MethodsWe retrospectively recorded the clinical data of patients with upper urinary tract calculi complicated by infection who have undergone Percutaneous nephrolithotomy(PCNL) in the Department of Urology, 2nd Affiliation Hospital of Kunming Medical University, from March to December 2021. Clinical data include general condition, laboratory index, CT, postoperative body temperature, heart rate, respiration, SIRS, sepsis, etc. Patients were divided into treated and control groups according to whether they had received a preoperative PA-MSHA injection. The two groups were compared for indices of inflammation and complications of infection after PCNL. Pre- and post-operative lymphocyte subsets and immunoglobulin changes were compared.Results115 patients were included in the study, including 43 in the treatment group and 72 in the control group. After Propensity Score Matching, 90 patients were divided into treatment (n=35) and control (n=55) groups. The postoperative inflammation index was higher in the treatment group than in the control group (P<0.05). The incidence of postoperative SIRS was higher in the treatment group than control (P<0.05). There were no cases of sepsis in either group. The double-positive T cells lymphocyte subsets were higher in the treatment group than in the control group ((P<0.05). Pre- and post-operative changes in immune function: total T lymphocyte count reduced, NK and NKT cell count increased in the control group, double-positive T cell count increased in the treatment group, IgG, IgA, IgM, complement C3 and C4 count reduced in both groups post-operatively.ConclusionThis study found that patients with upper urinary tract calculi and infection treated with antibiotic-based PA-MSHA before percutaneous nephrolithotomy had an increased inflammatory response after surgery, which may play a role in the prevention and treatment of sepsis. The percentage of double-positive T cells in the peripheral blood was increased after PA-MSHA treatment, which may have an immunomodulatory and protective effect in PCNL patients with stones complicated by infection.

Shared genetic correlations between kidney diseases and sepsis

“…However, research on the correlation between kidney stones, BUN, and NK cells is sparse. A study on urinary tract stones with infection noted changes in NK cells, but the specific mechanisms were not explored ( 72 ). Another study investigating risk factors for death in COVID-19 patients found that elevated urea nitrogen and NK cells correlated with a poor prognosis ( 73 ).…”

Trends in Anti-Tumor Effects of Pseudomonas aeruginosa Mannose-Sensitive-Hemagglutinin (PA-MSHA): An Overview of Positive and Negative Effects

“…In vivo and clinical data show that PA-MSHA can stimulate the immune response via the TLR4 signaling pathway and thus prevent the development of sepsis after surgery. PA-MSHA stimulated the release of serum pro-inflammatory mediators (TNF-α, IL-1β, and IL-6) 8 days after the intervention but increased anti-inflammatory mediators (IL-4 and IL-10) after 16 days, balancing the activity of the immune system to prevent infections [23,27]. PA-MSHAs immune-related and anti-tumor characteristics led to its approval in China in 1998 as a complementary cancer treatment that aims to boost patients' immune systems and thus improve the treatment of malignant tumors such as breast, gastric, bladder, hepatocellular, and colorectal [16,28,29].…”

“…Despite the fact that Pseudomonas aeruginosa is classified as an aerobe, it functions as a facultative anaerobe, capable of producing energy under oxygen-limited conditions by using alternative electron acceptors such as nitrate (NO 3 − ), nitrite (NO 2 − ), and nitrous oxide (N 2 O) [22]. While a live form of Pseudomonas aeruginosa is highly virulent and can cause fatal infections in humans, its inactivated, genetically modified form and its toxin, exotoxin A, have been proposed as potential immune-modulating and cytotoxic anti-tumor agents [23][24][25]. A genetically transformed subtype of Pseudomonas aeruginosa bacteria is called Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA), a bacteria killed at temperatures above 65 • C. It is a biologically engineered strain coated with fragile and straight MSHA (mannose-sensitive hemagglutination) fimbriae [26].…”

“…A genetically transformed subtype of Pseudomonas aeruginosa bacteria is called Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA), a bacteria killed at temperatures above 65 • C. It is a biologically engineered strain coated with fragile and straight MSHA (mannose-sensitive hemagglutination) fimbriae [26]. The MSHA surface decreases the toxic potential of Pseudomonas aeruginosa by preventing the expression of more harmful virulence factors on its surface [23]. In vivo and clinical data show that PA-MSHA can stimulate the immune response via the TLR4 signaling pathway and thus prevent the development of sepsis after surgery.…”