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Purpose of Review: Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts., Recent Findings: Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency., Summary: ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5-2.0 mL/min., Methods: Patients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra ® , CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra ® Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated., Results: Sixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103-108 to 23-28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L)., Conclusions: Subcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID., Trial Registration: NCT03033745.

Chronic lung disease is a complication of primary antibody deficiency (PAD) associated with significant morbidity and mortality. Manifestations of lung disease in PAD are numerous. Thoughtful application of diagnostic approaches is imperative to accurately identify the form of disease. Much of the treatment used is adapted from immunocompetent populations. Recent genomic and translational medicine advances have led to specific treatments. As chronic lung disease has continued to affect patients with PAD, we hope that continued advancements in our understanding of pulmonary pathology will ultimately lead to effective methods that alleviate impact on quality of life and survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Primary antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies. More severe forms of PADs-common variable immunodeficiency (CVID) and X-linked agammaglobulinemia (XLA)-require immunoglobulin replacement therapy (IRT) and may have serious complications. Differentiating severe PAD from milder hypogammaglobulinemia not requiring IRT can involve prolonged evaluations and treatment discontinuation. Severe PAD is defined by plasma cell deficiency, but this requires a biopsy to establish. Serum B-cell maturation antigen (sBCMA) is elevated in multiple myeloma, but levels are reduced among patients with myeloma in remission who have hypogammaglobulinemia., Objective: To measure the sBCMA level in 165 subjects to determine whether it differentiates severe PAD-CVID and XLA-from less severe forms not requiring IRT and those without PAD., Methods: sBCMA, B cells, and tissue plasma cells were measured among subjects with and without PAD, and correlated to clinical and laboratory data., Results: Subjects with an IgG level of less than 600 mg/dL had reduced sBCMA levels compared with subjects with PAD with IgG levels of greater than or equal to 600 mg/dL and controls without PAD. sBCMA level was lower in patients with CVID and XLA compared with patients with IgA or IgG deficiency and controls. sBCMA level correlated with gastrointestinal plasma cells. sBCMA level of less than 15 ng/mL had 97% positive predictive value for CVID or XLA, whereas 25 ng/mL or more had an 88% negative predictive value., Conclusions: sBCMA level is profoundly reduced in patients with severe PAD, including those with CVID and XLA and those with IgG levels of less than 600 mg/dL. sBCMA level measurement has potential to augment clinical evaluation of PAD. Prospective studies are needed to evaluate sBCMA for new PAD diagnosis and determine the necessity of IRT., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)