T Regulatory Cells in Hemodialysis Patients: Observational Study
Condition: Haemodialysis Complication; Immune Dysfunction
MeSH terms: Immune System Diseases
Study type: Observational

Summary: 
      In this observational study, the investigators evaluated the Treg number and function in a
      population of patients undergoing hemodialysis (HD).

      In particular, the investigators considered the relationship of Treg cell status with the
      different HD modalities and clinical parameters.
    

Detailed description: 
      Patients on hemodialysis (HD) present an elevated risk of cardiovascular disease, cancer and
      infectious events that may lead to the high morbidity and mortality rate characteristic of
      this population. Many causes can explain this increased risk, including inflammation that, in
      turn, might be secondary to dialysis-specific factors, such as contaminated water, dialysis
      modality and dialysis membranes used for treatment.

      In addition to chronic inflammatory, in HD patients is also present a significant alteration
      of the immune system resulting in chronic lymphocytic infiltration, alteration of T-helper
      balance (Th1/Th2) etc. The immune response is controlled by very complex mechanisms; it is
      mediated by interaction between antigen-presenting cells (APC), CD4+ T helper (Th) and T
      cells CD4+ CD25+ regulatory (Treg), a cell subpopulation of T CD4+ expressing the IL-2
      receptor (CD25) and forkhead factor (foxp 3). Treg cells contribute to the maintenance of
      peripheral tolerance by suppressing the immune response to self-normal or tumor antigens.
      Treg cells control population's expansion of peripheral cells and suppress the proliferation
      of Th activated cells. Accessory molecules such as CTLA-4 receptors, CD28 and IL-2 cytokines
      and IL-6, contribute to the activation and proliferation of Treg cells.

      The characterization by flow cytometry of Treg suffered for a lack of specific surface
      markers. These cells are generally identified on the basis of contemporary expression of
      molecules CD4 and CD25, but the specificity of these markers is limited, given that the CD25
      is also expressed on activated lymphocytes. Recently it has been showed that the expression
      of Foxp3 gene is a phenomenon strictly linked to the development of regulatory activity of
      Treg, and so, the extent of the expression of this gene by Real Time PCR is currently
      considered the most specific Treg marker. There is very poor data on Treg cells function in
      HD. A recent study shows that in patients on chronic HD, the number of Treg is lower if
      compared to healthy subjects. Moreover, the Treg cells of patients on HD would present a
      significant impairment of their function, assessed as the ability to inhibit lymphocyte
      proliferation.

      Those results, however, are affected by the lack of data on the characteristics of the
      studied patients and the type of dialysis treatment applied. In contrast, a recent study by
      our group showed that patients on hemodialysis with poor biocompatible membranes have a
      greater number of circulating Treg compared with healthy controls matched for age and sex.

      Given the absence of other data, it still remains to investigate the actual significance and
      function of Treg in HD, considering that Treg status might potentially affect the immune
      response.

      Therefore, the purpose of this study was to evaluate the structure and function of Treg cells
      in patients undergoing HD, also considering their relationship with the different HD
      modalities and clinical parameters.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        A total number of 30 prevalent patients undergoing chronic renal replacement terapy with
        hemodialysis (HD) has been included in the evaluation. The study duration was 12 months,
        with a check of the number and function of Treg every 3 months.

        During the study patients were subjected to dialysis and farmacology treatment as usual,
        without any alteration linked specifically to this protocol. The number and function of
        Treg were measured as a percentage of CD4+CD25bright+pre-dialysis in the last week of each
        third month of the study.
      
Biospecimen description: 
      Sample used to evaluate T cell subpopulations