Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

<div><p>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.</p></div

Diagnostic delay and the presence of bronchiectasis.

<p>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 <0.05 were considered significant).</p

Immunodeficiency cohort on Ig-replacement treatment.

<p>CVID indicates common variable immune deficiency; ALPS, autoimmune lymphoproliferative syndrome; and WHIM, warts hypogammaglobulinaemia infections and myelokathexis syndrome.</p

Likely cause of secondary antibody deficiency in each subject.

<p>CLL indicates chronic lymphocytic leukaemia; MM, multiple myeloma; MGUS, monoclonal gammopathy of unknown significance; RTX, Rituximab; RA, rheumatoid arthritis; and SLE, systemic lupus erythematosus.</p

Immunological parameters before Ig-replacement treatment.

<p>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.</p

Number of immunosuppressive therapies used by each group before symptom onset.

<p>Number indicates the number of therapies used (a single subject may have had more than one therapy).</p

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

<p>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<0.05, ** p<0.01, *** p<0.001; n.s. non-significant.</p

Ig-replacement therapy in primary and secondary antibody deficiency patients.

<p>Data were analysed with a two-tailed Mann-Whitney test; n.s., non-significant. IV indicates intravenous; and SC, sub-cutaneous.</p

Monitoring of molecular responses to tirabrutinib in a cohort of exceptional responders with relapsed/refractory mantle cell lymphoma

Publication status: PublishedFunder: King Faisal Medical City for Southern RegionsFunder: The Scott‐Waudby TrustFunder: Hope Against Cancer charit

Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures

Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza