Trauma as a Trigger for Autoimmunity

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Autoimmunity

Intervention / Treatment
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* Diagnostic Test: Comparison of the levels of antinuclear antibodies (ANA) by indirect immunofluorescence on a Hep-2 cell line.


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Comparison of the levels of antinuclear antibodies (ANA) by indirect immunofluorescence on a Hep-2 cell line.|To analyse whether patients with pertrochanteric femoral fracture with consecutive gamma-nailing develop any laboratory signs of transient autoimmunity (comparison of the levels of ANA; in order to overcome the problem of subjective semiquantitative evaluation, the novel method of automated digital fluorescence microscopy will be used)|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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trauma, immunological reaction to trauma, pertrochanteric femoral fracture, antinuclear antibodies, activation of innate immunity, adaptive immunity