Predominantly Antibody Deficiencies, Specific Antibody Deficiency
Conditions
Keywords
Specific Antibody Deficiency, Predominant antibody deficiencies, Ig replacement therapy
Brief summary
The DETECT study aims to demonstrate the importance of detecting SPAD in adult patients with recurrent benign and/or severe unexplained bacterial upper/lower respiratory tract infections. Unlike children in whom the deficit may be transient, long-term strategies are warranted in SPAD adult patients to prevent severe infections and lung disability. Beyond the diagnosis of this still unrecognized PID in adult patients, the investigators want to assess the impact of prophylactic antibiotics or IgRT on infections prevention and on quality of life in adult patients with the most severe clinical phenotypes, recurrent infections with high frequency of antibiotics take and/or recurrent infections with complications like bronchiectasis and/or severe infections requiring hospitalizations.
Detailed description
This multicenter observational prospective study will be conducted in 15 university or general hospitals, mostly centers included in the national network of the reference center CEREDIH. Pulmonologists, clinical immunologists and ENT specialists will be solicited in each center to refer patients for inclusions. All patients who fulfill eligibility criteria will be tested for anti-pneumococcal polysaccharides (PnPSs) response with the 23-valent pneumococcal (unconjugated) vaccine (PPV23) (V1, Day 0: blood sample anti-PnPS antibodies, and immunization; V2, Day 28-56): blood sample for anti-PnPS antibodies). If a SPAD would be diagnosed, the investigator will be free to consider prophylactic antibiotics and/or IgRT according to the medical history of the patient (notably in case of persistent infections while using prophylactic antibiotics). The efficiency on infections prevention and the impact on health-related quality of life (HRQoL) will be assessed 12 months after initiation of IgRT or prophylactic antibiotics (Visit 3).
Interventions
BIOLOGICALDiagnosis of SPAD using immunization with PPV23
Diagnosis of SPAD using immunization with PPV23
Sponsors
University Hospital, Lille
French Healthcare network for rare immune and hematological disorders (MARIH)
Takeda
VitalAire
Laboratoire français de Fractionnement et de Biotechnologies
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 65 year old patients * With a history of recurrent bacterial infections of upper and/or lower respiratory tract for at least 2 years, and fulfilling the specific following criteria: * Recurrent benign infections currently requiring 6 courses of antibiotics /year or more, or Bilateral bronchiectasis/bronchiolitis (after exclusion of cystic fibrosis and ciliary dyskinesia) AND recurrent benign infections currently requiring 3 courses of antibiotics /year or more or A history of severe upper/lower respiratory tract bacterial infection, and/or invasive infection with Streptococcus pneumonia, Streptococcus pyogenes or Haemophilus influenzae, which required hospitalization in the last 2 years, AND recurrent benign infections currently requiring 3 courses of antibiotics /year. * Normal serum IgG, IgA, IgM and IgG subclasses levels, normal CH50 and serum complement C3 and C4 proteins levels, normal T cells count * Normal B cell count, normal serum protein electrophoresis and immunofixation. (\* excepted for Pseudomonas aeruginosa colonization)
Exclusion criteria
* Any general condition that predisposes to infections: solid or hematological malignancies, diabetes mellitus, severe alcohol or intravenous drug abuse, chronic liver or kidney failure, human immunodeficiency virus infection, anatomic or functional asplenia, drug-induced 1 neutropenia, or solid organ or hematopoietic stem cell transplantation; * Any local predisposing factor to infections: cigarette smoking (\> 10 pack-year and/or 5 cigarettes/day), underlying infection (tuberculosis, influenza…), chronic obstructive pulmonary disease, oral, dental or skin conditions favorizing infections, streptococcal skin infections * Any other SID or PID diagnosed before inclusion * Pregnancy * PPV23 administration in the last 2 years (risk of hyporesponsiveness)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the frequency of SPAD in adult patients with unexplained recurrent bacterial respiratory infections | 4 to 8 weeks after immunization | Diagnosis of SPAD according to the AAAAI proposed consensus criteria for an impaired selective response to PS using immunization with PPV23 and assessment of anti-PnPS IgG response by the serotype-specific WHO-standardized ELISA 4 to 8 weeks after immunization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To describe infectious and non infectious associated diseases, including allergy and autoimmune diseases, in SPAD patients. | Througth study completion, an average 24 months | — |
| To assess the benefit of IgRT on the frequency of courses of antibiotic therapy. | Througth study completion, an average 24 months | Outcome measure: number of courses of antibiotics in the 12 months following IgRT start compared to the 12 months before IgRT |
| To assess the benefit of IgRT on QoL and daily life. | Througth study completion, an average 24 months | Outcome measure: number of missed work or school/university days in the 12 months following IgRT start compared to the 12 months before IgRT |
| To assess the benefit of prophylactic antibiotics on the frequency of courses of antibiotic therapy. | Througth study completion, an average 24 months | Outcome measure: frequency of courses of antibiotics in the 6 months following prophylaxis start compared to the 12 months before and/or number of patients switched to IgRT during the first 12 months. |
| To assess the benefit of prophylactic antibiotics on QoL and daily life. | Througth study completion, an average 24 months | Outcome measure: number of missed work or school/university days in the 12 months following prophylaxis start (or at the end of prophylactic antibiotics) compared to the 12 months before. |
| To collect serum and mononuclear cells for future research projects in SPAD and undiagnosed patients. | Througth study completion, an average 24 months | To collect serum and mononuclear cells for future research projects in SPAD and undiagnosed patients |
Countries
France
Contacts
CONTACTGuillaume LEFEVRE, MD,PhD
PRINCIPAL_INVESTIGATORGuillaume LEFEVRE, MD,PhD
University Hospital, Lille
Outcome results
None listed