Infections

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

COVID-19

IgA Deficiency

Pneumonia

Pneumonia, Viral

Communicable Diseases

Respiratory Tract Infections

Virus Diseases

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

Anti-Infective Agents

All Drugs and Chemicals

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Antibiotics, Antitubercular

Immunosuppressive Agents

Immunoglobulin A

Anne-Sophie KORGANOW, MD, PhD

Olivier VOLLMER, MD

Jeanne MALLICK, MD

Isabelle JAHN

The management of patients with a selective IgA deficiency currently consists of symptomatic treatment with treatment of infections by occasional or prolonged antibiotic therapy, immunosuppressive treatments for autoimmune pathologies, symptomatic treatment of allergic manifestations.

IVIG supplements are sometimes proposed in the event of recurrent infections and the demonstration of deficiencies in IgG subclasses (IgG1, 2, 3) often not sought for diagnosis The factors associated with the severity of clinical manifestations are not well identified and patients with IgA deficiency must be monitored over the long term because of the risk of the appearance of autoimmune manifestations and neoplasia. The identification of such factors could lead to the proposal of close monitoring for these patients.

IgA deficiency, which is frequent, has not been identified as a risk factor for severe COVID-19 infection, probably due to a lack of studies with sufficient recruitment. The therapeutic attitude concerning patients with an IgA deficiency in the event of COVID-19 infection is therefore not consensual.

There is currently no action to be taken regarding the risk of transmission of IgA deficiency.

Epidemiology of IgA Selective Deficiency - Clinical Manifestations and Risk of Transmission

Epidemiology of IgA Selective Deficiency - Clinical Manifestations and Risk of Transmission: A Retrospective Cohort Study in Strasbourg University Hospital

University Hospital, Strasbourg, France

Immunologic Deficiency Syndromes

Blood Protein Disorders

Hematologic Diseases

Syndrome

B-Lymphocyte Stimulator (BLyS)

This study will examine the safety of BlyS, an experimental drug being developed to treat immune deficiency. As of July 17, 2001, 7 persons with common variable immune deficiency (CVID) have received BlyS, with no problems reported. This study will test the safety of the drug in people with IgA deficiency.

Patients 18 years of age and older with IgA deficiency who have recurrent or chronic sinus or lung infections or chronic diarrhea or malabsorption may be eligible for this study. Candidates will be screened with a physical examination, blood and urine tests, electrocardiogram (EKG), chest X-ray and a breathing test (spirometry).

Participants will be divided into five groups of three persons each to receive different doses (0.1, 1, 5, 15 or 45 micrograms/kilogram of body weight) of BlyS. The first group will receive a single dose at the lowest dose level (0.l mg). Each succeeding group will receive a single higher dose following a 2-week observation period of the preceding group. The drug will be injected under the skin, with vital signs (temperature, pulse, blood pressure and breathing rate) monitored for one hour after dosing. Blood samples will be collected several times on the day of dosing (before the dose and at 1.5, 3, 5, 8 and 12 hours after the dose) and again at 1,2, 4, 8 and 12 weeks after the dose to measure BlyS levels and evaluate safety. Participants receiving one of the three higher doses will have additional blood samples collected 36, 48 and 60 hours after the dose. Blood will also be collected from all participants 6 and 12 months after dosing to look for any unexpected long-term effects. A total of 289 ml (1.2 cups) of blood will be collected.

Blood will be checked for changes in blood count, kidney and liver function, antibody levels and autoimmune problems. Saliva will be collected four times by placing a cotton ball in the mouth-once before the dose and three times after the dose-to measure antibody levels.

Urine samples will also be collected during the study.

B Lymphocyte Stimulator (BLyS (Trademark)) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that is expressed on peripheral blood monocytes and dendritic cells. Cellular receptors for BLyS are detected on mature immunoglobulin (Ig) expressing B-lymphocytes. In vitro studies show that BLyS increases B cell number, Ig production, antigen-specific immunoglobulin response, and induces production of secretory IgA.

B-cells collected from patients with Common Variable Immune Deficiency show evidence for BLyS binding to B cells and enhanced immunoglobulin secretion.

In 28-day toxicology studies in mice, pharmacological effects were restricted to B lymphoid tissues including B lymphocyte hyperplasia, increased splenic weight without significant increase in spleen size, and increased immunoglobulin production. Murine models suggest that all of the pharmacological effects are fully and rapidly reversible.

The biological profile of BLyS suggests that it may have therapeutic utility in the treatment of immunodeficiency disorders characterized by low or absent immunoglobulin such as selective IgA deficiency (IGA-D).

Risk that BLyS might contribute to IGA-D complications has been assessed. A series of special in vitro and short-term in vivo studies have shown BLyS does not enhance tumorigenicity or allergy/hypersensitivity. Enhanced autoimmunity with immune complex formation could not be ruled out in two mouse studies in which BLyS was administered at higher doses on multiple dosing schedules. Renal changes with glomerular protein deposits were noted in a subset of mice treated at 0.1 and 1.0 mg/kg in the first study and 0.3 and 3.0 mg/kg in the second study. Renal changes have not been reproducible in either of 2 repeat mouse studies designed to replicate conditions on the first study. Renal changes were not observed in the GLP toxicity study in which mice were treated for 4 weeks with BLyS followed by a 2-week recovery period, or in an exploratory monkey study.

This study is a phase I; single-dose, open-label, non-randomized, dose escalation study of BLyS administered subcutaneously to a total of 20 evaluable subjects with IgA-D. Each subject will receive a single dose of BLyS.

The proposed study consists of a screening phase, a 1-day treatment phase with pharmacokinetic sampling, day 2 and day 3 follow-up, and 1, 2, 4, 8, and 12-week acute safety evaluations. Dose escalation to the next cohort is dependent on results of the 2-week acute safety evaluation. Autoimmunity and interim infection history will be evaluated 4-6 weeks and 6 and 12 months. Long-term data will be collected on incidence of malignancy for a minimum of one year.

B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency

A Phase I Dose Escalation Study of B-Lymphocyte Stimulator (BLyS) Administered Subcutaneously in Patients With Selective IgA Deficiency

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Epidemiology of IgA Selective Deficiency - Clinical Manifestations and Risk of Transmission	NCT06125457	COVID-19		18 Years -	University Hospital, Strasbourg, France
B-Lymphocyte Stimulator (BLyS) To Treat Selective IgA Deficiency	NCT00024934	IgA Deficiency	B-Lymphocyte St...	-	National Institutes of Health Clinical Center (CC)
Epidemiology of IgA Selective Deficiency - Clinical Manifestations and Risk of Transmission	NCT06125457	COVID-19		18 Years -	University Hospital, Strasbourg, France

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