title: Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study.
abstract: A 5-years multicenter prospective study on 201 patients with common variable immunodeficiencies and 101 patients with X-linked agammaglobulinemia over a cumulative follow-up period of 1,365 patient-years was conducted to identify prognostic markers and risk factors for associated clinical co-morbidities, the effects of long-term immunoglobulin treatment and the IgG trough level to be maintained over time required to minimise infection risk. Overall, 21% of the patients with common variable immunodeficiencies and 24% of patients with X-linked agammaglobulinemia remained infection free during the study. A reduction of pneumonia episodes has been observed after initiation of Ig replacement. During the observation time, pneumonia incidence remained low and constant over time. Patients with pneumonia did not have significant lower IgG trough levels than patients without pneumonia, with the exception of patients whose IgG trough levels were persistently <400 mg/dL. In X-linked agammaglobulinemia, the only co-morbidity risk factor identified for pneumonia by the final multivariable model was the presence of bronchiectasis. In common variable immunodeficiencies, our data allowed us to identify a clinical phenotype characterised by a high pneumonia risk: patients with low IgG and IgA levels at diagnosis; patients who had IgA level <7 mg/dL and who had bronchiectasis. The effect of therapy with immunoglobulins at replacement dosage for non-infectious co-morbidities (autoimmunity, lymphocytic hyperplasia and enteropathy) remains to be established. A unique general protective trough IgG level in antibody deficiency patients will remain undefined because of the major role played by the progression of lung disease in X-linked agammaglobulinemia and in a subset of patients with common variable immunodeficiencies.
authors.affiliation: Department of Clinical Immunology, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy. isabella.quinti@uniroma1.it
authors.forename: Isabella
authors.initials: I
authors.lastname: Quinti
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Andrea
authors.initials: A
authors.lastname: Guerra
authors.forename: Roberto
authors.initials: R
authors.lastname: Rondelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spadaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Milito
authors.forename: Amelia Chiara
authors.initials: AC
authors.lastname: Trombetta
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.forename: Helene
authors.initials: H
authors.lastname: Martini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000368:Aged; D001987:Bronchiectasis / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D017074:Common Variable Immunodeficiency / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D015897:Comorbidity; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D050172:Genes, X-Linked; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D015994:Incidence; D007223:Infant; D007275:Injections, Intravenous; D007558:Italy; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G