Occurrence of Antibodies Cross-reacting With Autoantigens in Primary EBV Infection

NCT05127980 | Recruiting

• 1 other identifier: 2021-01338; am21Osthoff2
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess the occurrence of antibodies cross-reacting with autoantigens that have been detected in the context of SLE in patients with primary EBV infection over time compared to a control group. It is to establish a biobank of patients with primary EBV infection allowing to longitudinally analyze the immune response and its accompanying inflammatory processes with focus on the occurrence of antibodies cross-reacting with autoantigens associated with SLE and other autoimmune diseases. Substudies will analyze

• characteristics of primary EBV infection patients treated with antibiotics in comparison to patients treated without antibiotics and outcomes of these treatment regimens (occurrence of acute complications such as peritonsillar abscess (PTA) or need for tonsillectomy, frequency of fatigue or symptoms associated with chronic fatigue syndrome).
• Procalcitonin (PCT) concentrations in primary EBV infection compared to control patients with similar symptoms and its association with disease severity and local complications.
• the occurrence of fatigue and symptoms associated with chronic fatigue syndrome 6 and 12 months after primary EBV infection.

Conditions

Epstein-Barr Virus (EBV) Infection

Keywords

Infectious mononucleosis (IM); Viral capsid antigen (VCA); EBV nucleic antigen (EBNA); Systemic lupus erythematosus (SLE); Chronic fatigue syndrome (CFS); cross-reacting antibodies; molecular mimicry

Outcome Measures

Primary Outcomes (1)

• Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection

  Change in occurrence of antibodies cross-reacting with autoantigens in patients with primary EBV infection compared to a control group.

  at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)

Secondary Outcomes (5)

• Change in RNA expression profiles of peripheral blood cells

  at Visit 2 (day 1 (+ 1 day)), Visit 3 (3 months +/- 21 days), Visit 4 (6 months +/- 1 month) and Visit 5 (12 months +/-2 months)

• Change in Fatigue Assessment Scale (FAS)

  at month 6 and at month 12

• Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire

  at month 6 and at month 12

• Change in Procalcitonin (PCT) (Substudy Procalcitonin)

  on day 1 and day 3 (+/-1 day)

• Occurrence of acute complications such as PTA or need for tonsillectomy

  at Visit 2 (day 1 (+ 1 day)) and Visit 3 (3 months +/- 21 days),

Study Arms (2)

patients with confirmed primary EBV infection

40 patients with confirmed primary EBV infection as confirmed by the treating clinician and defined by: \- Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled) AND \- serology compatible with primary EBV infection (anti-EBNA IgG negative, anti-VCA IgG negative, anti-VCA IgM positive OR anti-EBNA IgG negative, anti-VCA IgG positive, anti- VCA IgM positive)

Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments); Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin); Other: Data collection: Patient reported outcome (Fatigue questionnaires)

control patients

40 control patients (Clinical picture of upper respiratory tract infection (including but not limited to tonsillitis/pharyngitis, malaise, headache, cough, rhinitis, cervical node enlargement)) and/ or confirmed primary Cytomegalovirus (CMV) infection

Other: Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments); Other: Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin); Other: Data collection: Patient reported outcome (Fatigue questionnaires)

Interventions

Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments) OTHER

Data collection: Participant characteristics (Illness course, complications of primary EBV infection and provided treatments) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months).

control patients; patients with confirmed primary EBV infection

Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin) OTHER

Data collection: blood samples (analysed for EBV serology, auto-antibody-testing/biobanking, RNA expression analyses, procalcitonin) during 12 months (baseline visit and follow-up visits at 3, 6 and 12 months).

control patients; patients with confirmed primary EBV infection

Data collection: Patient reported outcome (Fatigue questionnaires) OTHER

Data collection: Patient reported outcome (Fatigue questionnaires) at 6 and 12 months.

control patients; patients with confirmed primary EBV infection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Inpatients and outpatients with symptoms of infectious mononucleosis (IM) or a sore throat who are treated at the University Hospital of Basel will be approached.

You may qualify if:

• Informed consent as documented by signature
• Confirmed primary EBV infection as confirmed by the treating clinician and defined by:
• Compatible clinical (infectious mononucleosis symptoms including but not limited to malaise, headache, fever, tonsillitis, pharyngitis, cervical lymph nodes enlargement) and laboratory picture (lymphocyte count elevation, LUC cells, reactive lymphocytes in manual differential, elevated liver enzymes; of note, not all typically described features have to be fulfilled)
• AND
• serology compatible with primary EBV infection (anti-EBNA IgG negative, anti-VCA IgG negative, anti-VCA IgM positive OR anti-EBNA IgG negative, anti-VCA IgG positive, anti- VCA IgM positive).
• Informed consent as documented by signature.
• one of the following:
• Clinical picture of upper respiratory tract infection (including but not limited to tonsillitis/pharyngitis, malaise, headache, cough, rhinitis, cervical node enlargement)
• confirmed primary Cytomegalovirus (CMV) infection (an optimal control group; however, the number of patients with a diagnosis of primary CMV infection is limited).

You may not qualify if:

• Suspicion/diagnosis of IM as per judgement of the treating clinician (control group only); this individual may be eligible later for the IM group if primary EBV infection is confirmed, subsequently.
• Immunosuppression (broadly defined as primary/secondary immunodeficiency or treatment with an immunosuppressive medication including ≥ 10mg prednisone equivalent).
• History of autoimmune disease (e.g. SLE, vasculitis etc.)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Division of Internal Medicine

Basel, 4031, Switzerland

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood and serum samples will be coded by a study nurse and stored at -80°C in a dedicated freezer with limited access to unauthorized personal for future research projects.

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Infections; Infectious Mononucleosis; Lupus Erythematosus, Systemic; Fatigue Syndrome, Chronic

Interventions

Procalcitonin

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calcitonin; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Protein Precursors; Proteins

Study Officials

• Michael Osthoff, PD Dr. med.

  University Hospital Basel, Division of Internal Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Osthoff, PD Dr. med.

CONTACT

+41 61 328 68 28; michael.osthoff@usb.ch

Samuel Etienne

CONTACT

+41 61 556 5248; samuel.etienne@usb.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2021
• First Posted: November 19, 2021
• Study Start: October 15, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

CH (1)