Hypothesis / aims of study
Urinary tract infections (UTI’s) are one of the most frequent causes of infection in both community and hospital settings. (1) Diagnosis of UTI’s is conducted using urinary symptoms and urine culture (1). Presently investigation of recurrent urinary tract infections includes excluding anatomical abnormalities, functional disorders of the lower urinary tract, for example voiding dysfunction and metabolic disorders including diabetes mellitus. Previous studies into recurrent UTI’s describe risk factors that increase susceptibility such as: sexual intercourse, use of spermicides, previous UTI’s, history of maternal UTI and age at first UTI. The latter two suggesting a genetic aspect to susceptibility. However, there have been no previous studies to assess the association of the immune system and recurrent urinary tract infections. This study aims to identify if there are any immunological markers that are associated with a patient’s susceptibility to recurrent UTI’s.
Study design, materials and methods
This was a retrospective study of women attending the urogynaecology clinic in a tertiary centre. Women with vaginal prolapse, lower urinary tract symptoms or recurrent UTI can be referred to the clinic. At each visit, women had a urine analysis conducted alongside clinical evaluation. Urine microscopy and culture (UCEM) studies were requested depending on urinalysis and / or patient symptoms. Women were included in this study if they had had one or more urinary tract infection. Patients were classified as having recurrent urinary tract infections if they experienced three or more UTIs within a year, with a UTI requiring at least one microorganism to be cultured.
The following immunological investigations were also carried out as part of the regular assessment: IgA, IgM, IgG, IgG subclasses, serum diamine oxidase (DO) and mannose binding lectin (MBL). Patients requiring a cystoscopy and bladder biopsy had a mast cell analysis carried out on the biopsy sample. The mast cell count (MCC) was obtained using CD117 immuno-histochemical staining. A MCC of >28 mm2 was considered elevated.
Statistical analysis was performed using SPSS v26, Chicago, USA.
Results
In total 227 women were included in the study. The age range was 18 to 91 years. 124 women were classified as experiencing recurrent urinary tract infections. 103 women had 2 or less urinary tract infections within a year.
In total 34 different organism were identified from urine culture reports. The 5 most common organisms accounted for 73.5% of all positive results. These top 5 organisms were present on average 80.0% of the time at a concentration above 100,000 cfu/ml. The incidence of organisms found in urinary tract infections is presented in Table 1.
Overall, in 50.7% of urinary tract infections only one organism was cultured. Women who experienced recurrent UTI’s were more likely to have multiple organisms present during the infection, (Chi-squared = 33.852, p value = 5.946e-9). This suggests that if the urinary tract infection is caused by multiple organisms, women are more likely to be susceptible to recurrent UTI’s.
We compared the women with recurrent UTI’s and women with ≤2 UTI's in 1 year with overall IgG, IgM and IgA levels using a Chi-square test. No significant association was found (Table 2). A comparison with the IgG subclasses using a Chi-squared test was made (Table 2). Women with recurrent UTI’s were more likely to have low IgG2 levels (<2.4 g/L) compared with women experiencing ≤2 UTI’s in 1 year (Chi-squared= 8.562, p=0.003).
In addition, women with a low MBL were not at increased susceptibility to recurrent UTI’s (Chi-Squared= 0.316, p value= 0.574, t-test p value = 0.250).
From bladder biopsy results, women with recurrent UTI’s were not more likely to have an increased mast cell count (>28 mm2) (Chi-squared= 0.791, p value= 0.374) in the bladder mucosa.
The average age of menopause in the United Kingdom is 51 years of age. Of women experiencing recurrent UTI’s, 66.1% of them were pre-menopausal. Pre-menopausal women had an increased susceptibility to recurrent UTI ( p = 0.017) Chi-squared= 5.693. There was no association found with menopausal status and MBL levels.
Interpretation of results
This retrospective study has identified the association between low IgG2 levels and recurrent UTI’s which has previously not been shown. IgG1 and IgG2 are the predominant subclass contributors to the IgG class (2).
Present literature states a deficiency in mannose binding lectin is due to genetic predisposition and confers an increased susceptibility to recurrent infection (3). Studies have been conducted in respiratory tract infections however there is a lack of research investigating this theory in urinary tract infections. The study findings show that MBL is not thought to be a predisposing factor to recurrent urinary tract infections in women, even when assessed independently as pre and post-menopausal groups.