Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy

Abstract

We aimed to evaluate the role of the CD19 complex in the pathogenesis of transient hypogammaglobulinemia of infancy (THI) and to better characterize the subsets of memory B cells. The study population consisted of 22 male and 14 female patients with a mean age at presentation of 20 ± 9.9 months. The CD19 complex and B cell subsets were evaluated by flow cytometry. While the CD19 median fluorescence index (MFI) in patients with THI was significantly lower than controls (122.9 ± 66.7 in patients; 184.2 ± 39 in controls, p < 0.01), expression of CD21 and CD81 was increased (94.4 ± 3, 96.8 ± 2.5 % in patients; 91 ± 3.9; 94.7 ± 3.5 % in controls, p < 0.01 vs. p < 0.05, respectively). The expressions of switched memory B cells and IgM memory B cells were found to be reduced in THI. Considering that the CD19 complex regulates the events following antigen stimulation, the change in CD19 complex detected in THI may be related to insufficiency of antibody production.

Does Intravenous Immunoglobulin Therapy Prolong Immunodeficiency in Transient Hypogammaglobulinemia of Infancy?

“…2,14,22,23 Similarly, we had found both the initial lymphocyte subset percentages and their absolute counts to be in the normal range in our present and in our previous studies 9 . In the report by Artac et al, 24 T-cell, B-cell and NK-cell counts were also within normal ranges. Percentages of CD19 in B cells were normal, but CD19 median fluorescence intensity was lower in THI patients than in the control group.…”

Transient Hypogammaglobulinemia of Infancy

“…The authors found low intensity of CD19 expression, which they suggested could interfere with B cell activation, leading to diminished immunoglobulin production. 22 In contrast, Bukowska-Strakova et al evaluated the B cells of children with THI compared to normal control subjects. There were no differences between children with THI and control subjects of similar age.…”

“…Reviews of published series of infants and children diagnosed as having THI show relatively mild recurrent otitis media and upper respiratory infections to be the primary reason that immunoglobulin levels were determined. More serious infections are reported in some of these children, including pneumonia, 6,10,14 sepsis, 6,10,19,22 meningitis, 10,15,22 recurrent gastroenteritis, 10,14,22,24,25,29 recurrent urinary tract infections, 8,18,22,24 vaccine associated polio meningoencephalitis, 43 and deep tissue infections. 14,44 Opportunistic infections, including Pneumocystis jirovecii pneumonia 45 and chronic candidiasis, are also reported.…”

“…The authors concluded that the subset of putative THI patients who fail to achieve normal IgG levels have impaired terminal B cell development, a lesion that is shared with some CVID patients. 24 Artac et al 22 also evaluated the numbers of IgM1 and switched memory B cells, and reported findings These investigators also evaluated the status of the CD19 complex in THI by evaluating expression of CD19, CD21, and CD81. Since these molecules form a trimolecular complex which acts synergistically with the B cell receptor for B cell activation, their role in decreased immunoglobulin levels was investigated.…”

“…These are treated as they would be in any child, with appropriate antimicrobial therapy. A number of reports describe recurrent urinary tract infections in THI, 8,18,22,24 and it is important to rule out the possibility of anatomical abnormality contributing to this complication. Several papers describe hematologic disturbances in THI, including neutropenia and coexisting thrombocytopenia, but these problems appear to be uncommon and transient.…”