Identification of Predictive Blood Biomarkers of Recurrent Urinary Tract Infections

Identification of Predictive Blood Biomarkers of Recurrent Urinary Tract Infections

Urinary tract infections affect more than 130 million people worldwide each year. Almost 50% of women will have at least one urinary tract infection during their lifetime, usually cystitis. Half of them will have recurrent cystitis. Antibiotics are the first-line treatment for cystitis, but their effectiveness is decreasing due to the rapid spread of multi-resistant uro-pathogenic bacteria. The objective of this study is to identify blood biomarkers associated with a high risk of recurrent cystitis. Immune system cells, and more specifically innate immunity cells, play a key role in controlling urinary tract infections. In addition, clinical studies have shown that there is a high inter-individual variability in the ability of innate immune cells to respond to different stimuli. We therefore hypothesized that there was an association between the risk of recurrent cystitis and a deficiency of certain immune cell types in producing certain pro-inflammatory cytokines, including TNF-α, in response to one or more bacterial stimuli, particularly flagellin.

Inclusion Criteria:

• Female aged 18 to 28 years;
• Subject accepting to be serologically tested for HIV and HCV;
• Subject considered healthy by the physician on the basis of medical history and clinical examination;
• Subject with a body mass index between 18.5 and 30 kg/m2;
• Subject understands and speaks French and is able to give written consent;
• Subject affiliated to Social Security or a similar regime;
• Having reported a single cystitis since the age of 14 (Group 1), or 3 or more cystitis over a 12-month period since the age of 14 (Group 2).

Exclusion Criteria:

• Subject protected by law under guardianship or curatorship, or unable to participate in a clinical study under Article L. 1121-16 of the French Public Health Code;

• Subject who has participated in a clinical research study in the last 3 months in which he/she was exposed to a pharmaceutical product or medical device;

• Subject who has stayed in a tropical or subtropical country in the last 3 months;

• Pregnant or breastfeeding subject for women of childbearing age;

• Subject with special diet for medical reasons and prescribed by a doctor or dietician (e.g. a low-calorie diet or a diet intended to lower cholesterol levels);

• Subject who regularly consumes large quantities of alcohol, i. e. more than 50 g of pure alcohol per day (e. g. more than 4 glasses of 150 ml wine, more than 4 pints of 250 ml beer, or more than 4 glasses of 40 ml containing strong alcohol);

• Subject who has used an illegal recreational drug in the past 3 months;

• Subject who has taken an immunosuppressive or immunomodulatory drug (excluding intranasally or topically administered corticosteroids) in the past 2 weeks, or for more than 14 consecutive days in the past 6 months;

• Subject who has been vaccinated within the last 3 months;

• Subject who received a blood transfusion or immunoglobulins in the last 3 months;

• Subject stating that he has not been fasting for at least 10 hours;

• Subject reporting HIV or HCV status;

• Subject who had an infectious episode or was treated with antibiotics during the 4 weeks prior to the visit;

• Subject with a positive urinary pregnancy test;

• Subject with a severe and/or chronic and/or recurrent pathology, in particular:

  • A chronic inflammatory and/or autoimmune or allergic disease and in particular a chronic inflammatory disease of the intestine (Crohn's disease, ulcerative colitis), epidermis (psoriasis, atopic dermatitis), joints (rheumatoid arthritis), nervous system (multiple sclerosis), type I diabetes;
  • High blood pressure or type II diabetes;
  • A neurodegenerative disease.

• Subject who has been diagnosed with cancer and has not been in remission for more than 5 years.