Primary vs. secondary antibody deficiency: clinical features and infection outcomes of immunoglobulin replacement.

Sai S Duraisingham,Matthew Buckland,Sofia Grigoriadou,Hilary J Longhurst,Lorena Lorenzo,John Dempster,Matthaios Speletas

doi:10.1371/journal.pone.0100324

Sai S Duraisingham, Matthew Buckland + Show 5 more

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https://doi.org/10.1371/journal.pone.0100324

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Journal: PloS one	Publication Date: Jun 27, 2014
Citations: 106	License type: CC BY 4.0

Affiliation: Barts Health NHS Trust

Abstract

Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.

Highlights

Antibody deficiencies are defined by a loss of immunoglobulins or failure of immunoglobulin function, resulting in increased susceptibility to infection
Agammaglobulinaemia was characterised by panhypogammaglobulinaemia and infection onset,5 years of age – 11 subjects had X-linked agammaglobulinaemia (XLA) with a BTK mutation and one had autosomal recessive agammaglobulinaemia
The most common diagnosis in the primary group was common variable immune deficiency (CVID) accounting for 69.9% of the group, and 10.6% of the primary group had agammaglobulinemia

Summary

Introduction

Antibody deficiencies are defined by a loss of immunoglobulins or failure of immunoglobulin function, resulting in increased susceptibility to infection. Studies describe secondary antibody deficiencies as a result of haematological malignancy [6,7], immunosuppressive [8,9,10] or anticonvulsant medications [11], protein-losing enteropathy [12], nephrotic syndrome and trauma [13]. Antibody deficiencies are associated with infections, immune dysfunction, end organ damage and significant morbidity and mortality [14,15]. Immunoglobulin (Ig)-replacement for primary antibody deficiency is known to reduce infections, morbidity and mortality [16,17,18]. A small number of studies have demonstrated that (Ig)-replacement therapy is effective in reducing severe infections in those with secondary antibody deficiency as a result of a haematological malignancy [19,20,21,22]. Secondary antibody deficiencies are poorly described in the literature and clinical management guidance is usually extrapolated from experience with primary antibody deficiencies

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