Trauma as a Trigger for Autoimmunity (TATA)

Trauma as a Trigger for Autoimmunity - a Single Centre Observational Cohort Study

To analyse the immunological reaction to Trauma (pertrochanteric femoral fracture with consequent osteosynthesis) in the first weeks up to one year postoperatively with focus on the development of autoimmunity.

Study Overview

• Status: Completed
• Conditions: Autoimmunity
• Intervention / Treatment: Diagnostic test: Comparison of the levels of antinuclear antibodies (ANA) by indirect immunofluorescence on a Hep-2 cell line.

Detailed Description

This project represents a unique study of the influence of trauma on the immune system. It addresses the question whether an excess of apoptotic/necrotic cells can induce an at least transient autoimmune phenomena in humans. If the hypothesis of a transient induction of autoimmunity by trauma proves to be correct, this study will provide a novel insight into the pathogenesis of autoimmune diseases.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with acute pertrochanteric fracture in whom an operation (gamma-nail osteosynthesis) is planned at the University Hospital Basel.

Description

Inclusion Criteria:

• pertrochanteric femoral fracture (≤7 days)
• planned gamma nail osteosynthesis
• ability to give written informed consent

Exclusion Criteria:

• Severe hepatic and renal failure
• current active oncological disease
• current immunosuppressive or biological therapy
• known systemic autoimmune disease
• foreseeable lack of complete follow-up (e.g. due to generally poor health)
• cognitive impairment (delirium, dementia, alteration of consciousness)
• insufficient knowledge of project language
• pregnancy

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ANA	Fluorescence Index (FI) for ANA measurement (automated digital fluorescence microscopy = indirect immunofluorescence on a Hep-2 cell line). In order to overcome the problem of subjective semiquantitative evaluation, the novel method of automated digital fluorescence microscopy will be used (NOVA View, INOVA Diagnostics	Preoperative (1-2 days preoperative) and 12 weeks postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ANA	Fluorescence Index (FI) for ANA measurement (automated digital fluorescence microscopy)	6 weeks postoperative and 12 weeks postoperative and 12 months postoperative
Change in Antibody level against double stranded deoxyribonucleic acid (Anti-dsDNA)	serum level of Anti-dsDNA (U/ml)	Preoperative (1-2 days preoperative) and 6 weeks postoperative and 12 weeks postoperative and 12 months postoperative
Change in Antibody level against Anti-Cardiolipin	serum level of Anti-Cardiolipin (U/ml)	Preoperative (1-2 days preoperative) and 6 weeks postoperative and 12 weeks postoperative and 12 months postoperative
Change in Antibody level against complement component C1q (Anti-C1q)	serum level of C1q (U/ml)	Preoperative (1-2 days preoperative) and 6 weeks postoperative and 12 weeks postoperative and 12 months postoperative
Change in Antibody level against Sjögren's-syndrome-related antigen A (Anti-SSA/Ro)	serum level of Anti-SSA/Ro (U/ml)	Preoperative (1-2 days preoperative) and 6 weeks postoperative and 12 weeks postoperative and 12 months postoperative
Change in proportion of immune cells (Plasmablasts, regulatory T cell (T-regs), total Cluster of Differentiation (CD)4+, CD8+, CD19+, Natural killer (NK) cells	Change in proportion of immune cells (Plasmablasts, regulatory T cell (T-regs), total Cluster of Differentiation (CD)4+, CD8+, CD19+, Natural killer (NK) cells (cells/ml)	Preoperative (1-2 days preoperative) and 3-4 days postoperative and 6 weeks postoperative and 12 weeks postoperative
Change in serum levels of cytokines (Interleukin (IL)-6 , IL-10, IL-18, Tumor necrosis factor (TNF)-a , Tumor necrosis factor receptor two (TNF-RII)	Change in serum levels of cytokines (Interleukin (IL)-6 , IL-10, IL-18, Tumor necrosis factor (TNF)-a , Tumor necrosis factor receptor two (TNF-RII)	Preoperative (1-2 days preoperative) and 3-4 days postoperative and 6 weeks postoperative and 12 weeks postoperative

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Eliska Potlukova, PhD, Klinik für Innere Medizin, Universitätsspital Basel

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 4, 2016
• Primary Completion (ACTUAL): December 23, 2019
• Study Completion (ACTUAL): January 31, 2020

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (ACTUAL): December 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2020
• Last Update Submitted That Met QC Criteria: April 6, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: trauma; adaptive immunity; immunological reaction to trauma; pertrochanteric femoral fracture; antinuclear antibodies; activation of innate immunity
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Antinuclear
• Other Study ID Numbers: 2016-00895, me16Potlukova

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No