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Correlation of hypogammaglobulinaemia with proteinuria, and the relationship between hypogammaglobulinaemia and infection in active lupus nephritis
  1. Dawn Elaine Smilek1,2,
  2. Noha Lim3,
  3. Linna Ding4,
  4. Sara G. Murray5,
  5. Betty Diamond6 and
  6. David Wofsy7
  1. 1 Immune Tolerance Network, University of California San Franciso, San Francisco, California, USA
  2. 2 Division of Rheumatology, Department of Medicine, and the Lupus Nephritis Trials Network, University of California San Francisco, San Francisco, California, USA
  3. 3 Immune Tolerance Network, Massachusetts General Hospital, Bethesda, Maryland, USA
  4. 4 Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA
  5. 5 Division of Hospital Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, USA
  6. 6 Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, New York, USA
  7. 7 Division of Rheumatology, Department of Medicine, and the Russell/Engleman Research Center, University of California San Francisco, San Francisco, California, USA
  1. Correspondence to Dr Dawn Elaine Smilek; dsmilek{at}immunetolerance.org

Abstract

Objective To evaluate hypogammaglobulinaemia and risk of serious infectious adverse events in active lupus nephritis.

Methods The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared abatacept with placebo in participants with lupus nephritis undergoing treatment with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were assessed prior to initiation of treatment and throughout the trial. Hypogammaglobulinaemia was defined as IgG <450 mg/dL.

Results Hypogammaglobulinaemia was observed in 16/102 (15.7%) participants prior to initiation of induction therapy for active lupus nephritis. Participants with nephrotic range proteinuria were more likely to have hypogammaglobulinaemia, and serum IgG levels were inversely correlated with urine protein to creatinine ratio (r=−0.42, p<0.0001). Following initiation of treatment for active lupus nephritis, additional participants developed hypogammaglobulinaemia by weeks 2–4. Serum IgG levels then increased, and all but one participant had serum IgG ≥450 mg/dL at 24 weeks. Hypogammaglobulinaemia was not associated with an increased risk of serious infectious adverse events.

Conclusions In active lupus nephritis in ACCESS, hypogammaglobulinaemia was common and inversely correlated with proteinuria. Serum IgG levels were lowest in the weeks immediately following initiation of induction therapy, and subsequently improved by 24 weeks. Hypogammaglobulinaemia was not associated with serious infectious adverse events.

  • Cyclophosphamide
  • Infections
  • Lupus Nephritis

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/lupus-2017-000229

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    Footnotes

    • Contributors DES, LD, SGM, BD and DW designed the study. LD, BD and DW participated in data acquisition. All authors participated in analysis and interpretation of data. All authors participated in developing the manuscript and approved the final version to be published.

    • Funding This study was conducted by the Immune Tolerance Network. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers NO1AI15416 and UM1AI109565. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Study medication was provided by Bristol-Myers Squibb.

    • Competing interests DW has received consulting fees, speaking fees and/or honoraria from Genentech and GlaxoSmithKline.

    • Ethics approval Received institutional review or ethics board approval at each clinical site.

    • Provenance and peer review Not commissioned; internally peer reviewed.