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Protein-losing Enteropathy as a Complication and/or Differential Diagnosis of Common Variable Immunodeficiency

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Journal of Clinical Immunology Aims and scope Submit manuscript

A Correction to this article was published on 26 August 2022

This article has been updated

Abstract

As protein-losing enteropathy (PLE) can lead to hypogammaglobulinemia and lymphopenia, and since common variable immunodeficiency (CVID) is associated with digestive complications, we wondered if (1) PLE could occur during CVID and (2) specific features could help determine whether a patient with antibody deficiency has CVID, PLE, or both. Eligible patients were thus classified in 3 groups: CVID + PLE (n = 8), CVID-only (= 19), and PLE-only (n = 13). PLE was diagnosed using fecal clearance of α1-antitrypsin or 111In-labeled albumin. Immunoglobulin (Ig) A, G, and M, naive/memory B and T cell subsets were compared between each group. CVID + PLE patients had multiple causes of PLE: duodenal villous atrophy (5/8), nodular follicular hyperplasia (4/8), inflammatory bowel disease-like (4/8), portal hypertension (4/8), giardiasis (3/8), and pernicious anemia (1/8). Compared to the CVID-only group, CVID + PLE patients had similar serum Ig levels, B cell subset counts, but lower naive T cell proportion and IgG replacement efficiency index. Compared to the CVID-only group, PLE-only patients did not develop infections but had higher serum levels of IgG (p = 0.03), IgA (p < 0.0001), and switched memory B cells (p = 0.001); and decreased naive T cells (CD4+: p = 0.005; CD8+: p < 0.0001). Compared to the PLE-only group, CVID + PLE patients had higher infection rates (p = 0.0003), and lower serum Ig (especially IgA: p < 0.001) and switched memory B cells levels. In conclusion, PLE can occur during CVID and requires higher IgG replacement therapy dosage. PLE can also mimic CVID and is associated with milder immunological abnormalities, notably mildly decreased to normal serum IgA and switched memory B cell levels.

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Data Availability

The datasets generated during and/or analyzed during the current study, as well as statistical analyses codes, are available from the corresponding author on reasonable request.

Change history

  • 25 August 2022

    The original version of this paper was updated to present the correct corresponding author and the correct name of the first author

  • 26 August 2022

    A Correction to this paper has been published: https://doi.org/10.1007/s10875-022-01356-9

Abbreviations

CVID:

Common variable immunodeficiency

IBD:

Inflammatory bowel disease

Ig:

Immunoglobulin

IV:

Intravenous

MZ:

Marginal zone

NRH:

Nodular regenerative hyperplasia

NS:

Non-significant

PID:

Primary immunodeficiency

PIL:

Primary intestinal lymphangiectasia

PLE:

Protein-losing enteropathy

SC:

Subcutaneous

Sw Mem:

Switched memory

TCM:

Central memory T cells

TEM:

Effector memory T cells

TEMRA:

Terminal effector memory T cells

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Author notes

  1. Sébastien Sanges and Nicolas Germain contributed equally to this work.

Authors and Affiliations

  1. Université de Lille, UFR Médecine, 59000, Lille, France

    Sébastien Sanges, Nicolas Germain, Sarah Stabler, David Launay, Éric Hachulla, Damien Huglo, Sylvain Dubucquoi, Myriam Labalette & Guillaume Lefèvre

  2. Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France

    Sébastien Sanges, David Launay, Éric Hachulla, Sylvain Dubucquoi, Myriam Labalette & Guillaume Lefèvre

  3. Service de Médecine Interne Et Immunologie Clinique, Centre de Référence Des Maladies Auto-Immunes Systémiques Rares du Nord Et Nord-Ouest de France (CeRAINO), CHU Lille, 59000, Lille, France

    Sébastien Sanges, Nicolas Etienne, Louis Terriou, David Launay & Éric Hachulla

  4. Health Care Provider of the European Reference Network On Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET), Lille, France

    Sébastien Sanges, David Launay & Éric Hachulla

  5. CHU Lille, Institut d’Immunologie, 59000, Lille, France

    Nicolas Germain, Sylvain Dubucquoi, Myriam Labalette & Guillaume Lefèvre

  6. Unité de Lymphologie, Hôpital Cognacq-Jay, Paris, France

    Stéphane Vignes

  7. Département de Nutrition, CHU Lille, 59000, Lille, France

    David Séguy

  8. Département de Maladies Infectieuses, CHU Lille, 59000, Lille, France

    Sarah Stabler

  9. Département de Médecine Nucléaire, CHU Lille, 59000, Lille, France

    Damien Huglo

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  1. Sébastien Sanges
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Contributions

Each individual named as an author meets the ICMJE criteria for authorship. SS, NG, and GL conceived and designed the study. SS and NG screened patients and collected clinical and biological data. DH performed 111In-labeled albumin fecal clearance. SS and NG constituted and managed the database. SS and NG performed statistical analyses and created the figures. SS wrote the first draft of the manuscript. GL made major revisions to the manuscript. SV and DS provided their expertise in protein-losing enteropathies. SSa and NE provided their expertise in infectious diseases. LT, DL and EH provided their expertise in clinical immunology and immunodeficiencies. SD and ML provided their expertise in basic immunology. All authors read and approved the submitted version.

Corresponding author

Correspondence to Guillaume Lefèvre.

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Conflict of Interest

SS reports travel/accommodation expenses from Shire. DL reports grants and personal fees from Octapharma and CSL Behring; grants from Grifols. GL received advisory fees from Shire and Takeda, travel/accommodation expenses from Octapharma, and research grants from LFB, Takeda, Octapharma, CSL Behring. NG, SV, DS, SaS, NE, LT, DH, EH, SD, ML report no conflict of interest related to this work.

Ethics Approval

The study complied with the recommendations of the Helsinki declaration. French legislation on non-interventional studies does not require ethics committee approval for the use of de-identified data collected during patient care. As such, the need for an ethics committee approval was waived for this study by the “Comité de Protection des Personnes” (CPP). The data were de-identified and complied with the requirements of the “Commission Nationale de l’Informatique et des Libertés” (CNIL), the organization responsible for ensuring the ethical use of data collected for scientific purposes in France. The CNIL approved the methods used to collect and analyze data from our patient database (approval #DEC20-229).

Consent to Participate and to Publish

French legislation on noninterventional studies requires collecting the non-opposition of patients but does not require written consent. As such, non-opposition was obtained from each patient included in the study for the use and publication of their de-identified medical record data.

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Sanges, S., Germain, N., Vignes, S. et al. Protein-losing Enteropathy as a Complication and/or Differential Diagnosis of Common Variable Immunodeficiency. J Clin Immunol 42, 1461–1472 (2022). https://doi.org/10.1007/s10875-022-01299-1

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