Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies

Milito, Cinzia; Pulvirenti, Federica; Cinetto, Francesco; Lougaris, Vassilios; Soresina, Annarosa; Pecoraro, Antonio; Vultaggio, Alessandra; Carrabba, Maria; Lassandro, Giuseppe; Plebani, Alessandro; Spadaro, Giuseppe; Matucci, Andrea; Fabio, Giovanna; Dellepiane, Rosa Maria; Martire, Baldassarre; Agostini, Carlo; Abeni, Damiano; Tabolli, Stefano; Quinti, Isabella

doi:10.1016/j.jaci.2019.01.051

Cited by 62 publications

(48 citation statements)

References 34 publications

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“…29,30 Prophylactic antibiotics, such as azithromycin, are widely used in various doses, and in a recent study are clearly of benefit in reducing respiratory exacerbation and chronic infection-related pulmonary disease. 31 However, as for other inflammatory conditions in CVID, these measures will not treat or reverse noninfectious interstitial lung disease, and more aggressive management is usually required to prevent scarring and permanent lung damage. 32 Low doses of corticosteroids may be used acutely but have limited benefit long term.…”

Section: Autoimmune Pulmonary Diseasementioning

confidence: 99%

Autoimmunity in common variable immunodeficiency

Agarwal

Cunningham‐Rundles

2019

Annals of Allergy, Asthma & Immunology

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Key MessagesBesides infections, autoimmune or inflammatory diseases are common in patients with primary immunodeficiency. Common organspecific autoimmunity in CVID patients include the gastrointestinal tract, lung, hematological system, joints, and skin.The onset of autoimmune disease in CVID varies, as does the severity and progression.Treatment of autoimmunity is often complicated by drug adverse effects and prolonged immunosuppression but includes high-dose immunoglobulin, corticosteroids, selected immunosuppressants, and other immune modulators.The mechanisms of these autoimmune/inflammatory diseases are still being investigated but likely involve defects in central and peripheral tolerance and autoreactive T and B cells. A B S T R A C TObjective: Common variable immunodeficiency (CVID) is a primary immunodeficiency that is clinically heterogeneous, characterized by both infectious and noninfectious complications. Although the hallmark of disease presentation is commonly a history of recurrent sinopulmonary infections, autoimmunity and noninfectious inflammatory conditions are increasingly associated with CVID. Data Sources: A comprehensive literature search using PubMed of basic science and clinical articles was performed. Study Selections: Articles discussing the association of autoimmunity with primary immunodeficiency, specifically CVID, were selected. Results: The most common autoimmune conditions are cytopenias, including immune thrombocytopenia purpura and hemolytic anemia, but organ-specific autoimmune/inflammatory complications involving the gastrointestinal, skin, joints, connective tissue, and respiratory tract. In most cases, immunoglobulin replacement therapy does not ameliorate or treat these inflammatory complications, and additional immunomodulatory treatments are needed. Conclusion: Mechanisms producing these conditions are poorly understood but include cytokine and cellular inflammatory pathways, and loss of tolerance to self-antigens through the multiple signaling molecules and pathways common to tolerance and immune deficiency.

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Section: Autoimmune Pulmonary Diseasementioning

confidence: 99%

Autoimmunity in common variable immunodeficiency

Agarwal

Cunningham‐Rundles

2019

Annals of Allergy, Asthma & Immunology

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“…In particular, in the 6-years longitudinal study, we have evaluated the potential predictive value of the residual capacity to mount a specific IgA response. The inability to mount an IgA-mediated response against the pneumococcal polysaccharide antigens or the inability to maintain the antibody response over time was associated to a greater frequency of URTI and LRTI exacerbations due to a variety of pathogens (24,25) during FU, to chronic lung damage and to a greater risk to develop non-infectious complications, autoimmunity and chronic diarrhea during the observation period. In contrast, CVID patients with IgA-mediated response had a reduced risk of clinical complications in the years following post-vaccination assessment.…”

Section: Discussionmentioning

confidence: 99%

“…The evaluation of anti-PnPS23 IgA has been shown to be a prognostic marker, allowing to identify good and poor CVID responders. We suggest to add this test to identify patients with serious immunological impairment, a greater risk of co-morbidity and a worse prognosis who could benefit from closer clinical monitoring, and from additional preventive measures, including antibiotic prophylaxis (24). We suggest that antibody titers should be measured at ∼4 weeks after immunization.…”

Section: Discussionmentioning

confidence: 99%

IGA Antibody Induced by Immunization With Pneumococcal Polysaccharides Is a Prognostic Tool in Common Variable Immune Deficiencies

et al. 2020

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The evaluation of the response to vaccination in patients with inborn errors of immunity is a tool to evaluate T-dependent and T-independent antibody residual function of B lymphocytes and it is part of the diagnostic definition for Common Variable Immune Deficiencies. Currently used classifications for Common Variable Immune Deficiencies patients are based on the frequency of B cell subsets, and have been proven as a valid instrument for identification of patients at higher risk of infectious and non-infectious complications. This 6-years period observational study delineated the measurement of specific IgA antibodies induced by a 23-valent pneumococcal polysaccharides vaccine by a standardized ELISA for the quantification of IgA antibodies to all 23 pneumococcal serotypes as an additional prognostic marker in 74 CVID patients. The inability to mount an IgA-mediated response against the pneumococcal polysaccharide antigens or the inability to maintain the antibody response over time identified poor IgA CVID responders with severe immunological impairment, great risk of co-morbidities, and poor prognosis. The division of CVID patient into specific IgA-non responders and IgA-responders discriminated better than other CVID classifications for infectious risk, while it overlapped for non-infectious complications. Our study suggested to add the evaluation of the antibody response by the 23-valent IgA assay in the clinical monitoring of CVID patients.

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“…Management is based on the clinical phenotype. Most patients with "infection-only" phenotype are sufficiently cared for by regular immunoglobulin replacement therapy and adequate antibiotic treatment of breakthrough infections, with a few patients especially with bronchiectasis or chronic upper-airway disease profiting from additional prophylactic antibiotic treatment (Milito et al 2019). Patients with a complex form of disease frequently require additional treatment depending on the type of secondary complications.…”

Section: Managementmentioning

confidence: 99%