Immunoglobulin Efficacy and Immune Profiling in Antibody Immunodeficiency (IEIPAI)

Real-world Efficacy of Immunoglobulin in Antibody Immunodeficiency: A Prospective Cohort Study Based on T/B Cell Subset Profiling

This study aims to systematically evaluate the dynamic alterations in peripheral immune subsets among patients with antibody Immunodeficiency undergoing Immunoglobulin therapy

Study Overview

• Status: Not yet recruiting
• Conditions: Primary Immunodeficiency Diseases

Detailed Description

Antibody Immunodeficiency（AID） represent a heterogeneous group of inborn errors of immunity characterized by defective antibody production, predisposing patients to recurrent infections, chronic inflammation, and paradoxical autoimmune manifestations. While Immunoglobulin replacement therapy serves as the cornerstone of management, patient clinical trajectories and responses to treatment remain highly variable. The underlying immunological defects-particularly the impaired cross-talk between T and B lymphocytes-are critical to understanding the pathogenesis and phenotypic diversity of AID.

This single-center, prospective observational study is designed to systematically characterize the dynamic alterations in peripheral immune subsets among patients with antibody immunodeficiency, with a specific focus on T-B cell interactions. By employing high-resolution multiparametric flow cytometry, we will perform comprehensive profiling of critical lymphocyte subpopulations. B-cell evaluation will quantify switched memory B cells, non-switched memory B cells, plasmablasts, and double-negative B cells. Concurrently, T-cell profiling will assess circulating follicular helper T cells (pTfh), regulatory T cells (Tregs), and overarching CD4+ and CD8+ compartments.

Participants will undergo baseline clinical and immunological evaluation prior to or during steady-state immunoglobulin therapy, followed by prospective longitudinal assessments. We hypothesize that specific baseline immune signatures (e.g., skewed pTfh proportions or expanded DN B cells) may serve as predictive biomarkers for the frequency of breakthrough infections and the development of autoimmune complications. Furthermore, this study will investigate the potential long-term immunomodulatory effects of immunoglobulin on restoring cellular homeostasis.

Ultimately, by correlating deep immunophenotyping data with real-world clinical outcomes-specifically annualized infection rates, specific antibody responses, and IgG trough levels-this study aims to elucidate the mechanisms driving clinical heterogeneity in AID and provide an evidence base for more personalized, targeted therapeutic strategies.

• Study Type: Observational
• Enrollment (Estimated): 15

Contacts and Locations

• Study Contact: Name: Jing He; Phone Number: +86 18611707347; Email: hejing1105@126.com
• Study Contact Backup: Name: Linger Guan; Phone Number: +86 15196110113; Email: gleyyfoya@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary antibody immunodeficiency, aged 18 years and older, who are receiving regular immunoglobulin replacement therapy at the study site. Exclusion criteria include active infection, recent immunosuppressive treatment, or prior hematopoietic stem cell transplantation.

Description

Inclusion Criteria:Confirmed Diagnosis: Diagnosis of primary antibody immunodeficiency based on clinical presentation and laboratory evidence of impaired antibody production. Diagnoses should align with standard criteria (e.g., ESID/IUIS diagnostic criteria).

Laboratory Evidence: Documented quantitative deficiency in serum immunoglobulins, defined as reduced IgG, IgA, and/or IgM levels below the age-adjusted lower limit of normal, and/or demonstrated poor specific antibody response to vaccines.

Age: Patients aged between 5 and 50 years (inclusive) at the time of screening. Treatment Status: Currently receiving or scheduled to initiate regular immunoglobulin replacement therapy.

Consent: Provision of written informed consent by the patient or their legal guardian, along with documented assent from pediatric participants where developmentally appropriate.

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Exclusion Criteria:Secondary Immunodeficiency: Presence of other severe comorbidities that may affect immune function. This specifically includes secondary causes of hypogammaglobulinemia, such as active malignancies, protein-losing enteropathy, nephrotic syndrome, or untreated HIV infection.

Other PIDs: Confirmed diagnosis of primary immunodeficiency disorders other than predominantly antibody deficiency.

Confounding Medications: Use of systemic immunosuppressive or targeted immunomodulatory drugs within 3 months prior to enrollment. Patients on stable immunoglobulin replacement therapy are exempt from this exclusion.

Acute Confounding Illness: Presence of active, severe, uncontrolled infections at the time of baseline blood sampling that, in the investigator's clinical judgment, would transiently distort baseline immune subset profiling.

Pregnancy/Lactation: Current pregnancy or breastfeeding, due to the physiological alterations in maternal immune subsets.

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Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Antibody Immunodeficiency Cohort; Prospective cohort of patients with antibody immunodeficiency, receiving standard immunoglobulin replacement therapy. Immune profiling (T/B cell subsets) will be performed to evaluate real-world efficacy and immune reconstitution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peripheral Blood T-cell and B-cell Subsets	Quantification of the absolute counts and percentages of specific lymphocyte subsets to evaluate the T-B cell interaction. B-cell subsets include switched memory B cells, non-switched memory B cells, plasmablasts, and double-negative (DN) B cells. T-cell subsets include circulating follicular helper T cells (pTfh), CD4+ T cells, CD8+ T cells, and regulatory T cells (Tregs). Measurements will be performed using high-resolution multiparametric flow cytometry.	Baseline (Month 0), Month 6, and Month 12.
Annualized Infection Rate (AIR)	The primary clinical efficacy outcome is the incidence of breakthrough infections. This is defined as the number of severe or moderate infection episodes per patient per year requiring hospitalization, intravenous antibiotics, or prolonged oral antibiotics (>7 days).	Prospectively assessed from Baseline up to Month 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Immune Phenotypes and IgG Trough Levels	Assessment of the statistical correlation between dynamic changes in critical immune subsets (e.g., pTfh and DN B cells) and steady-state serum IgG trough levels measured immediately prior to routine immunoglobulin. This aims to establish immunological biomarkers for optimal immunoglobulin dosing.	Baseline (Month 0), Month 6, and Month 12.
Incidence and Evolution of Autoimmune Manifestations	Proportion of patients developing new-onset autoimmune complications or experiencing exacerbations of preexisting autoimmune conditions (such as immune cytopenia, autoimmune enteropathy, or interstitial lung disease) during the follow-up period.	Prospectively assessed from Baseline up to Month 12.

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Zhanguo Li, Study Principal Investigator Peking University Institute of Rheuamotology and Immunology

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: March 31, 2026
• First Submitted That Met QC Criteria: March 31, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Immunologic Deficiency Syndromes; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases
• Other Study ID Numbers: 20260330 IVIG-AID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in this article will be shared. Data will be available beginning 6 months and ending 36 months following article publication, to researchers who provide a methodologically sound proposal approved by an independent review committee, for the purpose of achieving the aims in the approved proposal. Proposals should be directed to the corresponding author.
• IPD Sharing Time Frame: Will be available beginning 6 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: De-identified individual participant data (IPD) will be accessible to researchers who submit a methodologically sound research proposal that is approved by an independent review committee. Access is limited to achieving the aims specified in the approved proposal. Proposals should be directed to the corresponding author of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No