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

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

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.

Conflict of interest statement

Competing Interests: HJL and members of her department have received funding to attend conferences and other educational events, donations to her departmental fund and/or have participated in clinical trials with the following immunoglobulin manufacturers: BPL, CSL Behring, Octapharma, Baxter, Grifols and LFP. She has been a member of the medical advisory panel for Baxter and CSL. SD is funded by a grant from CSL Behring. MB has been a medical advisor to Octopharma and received funding for educational events from Octopharma and CSL Behring. SG has been a CI/PI or co-investigator for clinical trials with Baxter, Octapharma, CSL Behring and has received funding for educational events from BPL, Octapharma and CSL Behring. JD has acted as a nurse advisor to CSL Behring and Octapharma. LL has received funding from Grifols to attend educational events and conferences.

Figures

Figure 1. Diagnostic delay and the presence…
Figure 1. Diagnostic delay and the presence of bronchiectasis.
Diagnostic delay (time between symptom onset and antibody deficiency diagnosis) was determined for the primary (n = 58) and secondary (n = 25) groups (A). The percentage of subjects with or without bronchiectasis (determined by high-resolution CT scan) is shown for each group (B). Diagnostic delay by bronchiectasis presence or absence is shown for the primary (n = 45) and secondary (n = 21) groups (C). The bars in panels A and C represent median values. Data in panel A were analysed by a two-tailed unequal variance t-test and data in panel C were analysed by a two-tailed Mann-Whitney test; n.s. non-significant (p values

Figure 2. Immunological parameters before Ig-replacement treatment.

Figure 2. Immunological parameters before Ig-replacement treatment.

Serum IgG (A), IgA (B) and IgM (C)…

Figure 2. Immunological parameters before Ig-replacement treatment.
Serum IgG (A), IgA (B) and IgM (C) levels in the year before Ig-replacement are shown for the primary (n = 58) and secondary groups (n = 27). Each symbol represents the mean value over the year for one subject and the bars represent the group median. The frequency of switched memory B cells (CD19+CD27+IgD−IgM−) as a proportion of peripheral blood B cells is shown for the primary (n = 50) and secondary (n = 10) groups (D). Dotted lines indicate the normal reference ranges for each. Data in panels A–C were analysed by a two-tailed unequal variance t-test and data in panel D were analysed by a two-tailed Mann-Whitney test; * p<0.05, ** p<0.01; n.s. non-significant.

Figure 3. Number of serious and non-serious…

Figure 3. Number of serious and non-serious infections before and after Ig-replacement treatment.

The number…

Figure 3. Number of serious and non-serious infections before and after Ig-replacement treatment.
The number of serious infections requiring hospitalisation or IV antibiotics and the number of patient-reported non-serious infections in the year preceding Ig-replacement treatment (A–B) and in the year 2012/2013 (C–D) is shown. The bars represent the group medians. Serious (E) and non-serious infections (F) are shown for each patient before (filled symbols) and after (open symbols) treatment. Data in panels A–D were analysed by a two-tailed unequal variance t-test and data in panels E–F were analysed by a two-tailed paired t-test; * p
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    1. Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, et al. (2013) A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. J Clin Immunol 33: 1078–1087. - PMC - PubMed
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SD's salary was funded by CSL Behring. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Figure 2. Immunological parameters before Ig-replacement treatment.
Figure 2. Immunological parameters before Ig-replacement treatment.
Serum IgG (A), IgA (B) and IgM (C) levels in the year before Ig-replacement are shown for the primary (n = 58) and secondary groups (n = 27). Each symbol represents the mean value over the year for one subject and the bars represent the group median. The frequency of switched memory B cells (CD19+CD27+IgD−IgM−) as a proportion of peripheral blood B cells is shown for the primary (n = 50) and secondary (n = 10) groups (D). Dotted lines indicate the normal reference ranges for each. Data in panels A–C were analysed by a two-tailed unequal variance t-test and data in panel D were analysed by a two-tailed Mann-Whitney test; * p<0.05, ** p<0.01; n.s. non-significant.
Figure 3. Number of serious and non-serious…
Figure 3. Number of serious and non-serious infections before and after Ig-replacement treatment.
The number of serious infections requiring hospitalisation or IV antibiotics and the number of patient-reported non-serious infections in the year preceding Ig-replacement treatment (A–B) and in the year 2012/2013 (C–D) is shown. The bars represent the group medians. Serious (E) and non-serious infections (F) are shown for each patient before (filled symbols) and after (open symbols) treatment. Data in panels A–D were analysed by a two-tailed unequal variance t-test and data in panels E–F were analysed by a two-tailed paired t-test; * p

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