Abnormal immunoglobulin expression and B-cell follicle organization in inborn errors of immunity/primary...

Patients with inborn errors of immunity/primary immunodeficiency (IEI/PID) frequently present with reactive lymphadenopathy which is biopsied to rule out lymphoma or infection. We asked whether reactive lymphoid tissue from an international cohort of 35 patients with IEI/PID contains diagnostic clues to the underlying immune dysfunction as compared to 13 control pediatric patients. To this end, we investigated abnormalities of B-cell follicle architecture and Immunoglobulin G (IgG) + class-switched (CS) versus IgM/IgD + non-IgG-CS Ig production. Abnormalities of B-cell follicles including absent or naked germinal centers (GCs) and/or increased T follicular helper(TFH) cells within GCs were seen in 45.7% (16/35) of IEI/PIDs and 15.4% (2/13) of controls (X² = 3.7520, p = 0.054). There was a statistically significant association of B-cell follicle abnormalities with infectious (X² = 5.148, p = 0.023) but not autoimmune history. Abnormal IgM + , IgD + , IgG + and/or CD138 + plasmablast/plasma cell (PB/PC) density was observed in 79.4% of IEI/PIDs (27/34) as compared to 7.7% of controls (1/13, X² = 20.085, p < 0.001). Isolated deficiency of IgG CS PB/PC was present in 42% (12/33) of IEI/PID biopsies and in no control patients, 0% (0/13, X² = 6.396, p = 0.011). There was a strong and highly statistically significant positive correlation between IgG + PB/PC density and serum IgG (Kendall's tau-b 0.567, asymptotic standard error 0.129, approximate significance < 0.001). There was also a statistically significant association of PB/PC abnormalities with infectious (X² = 12.024, p < 0.001) but not autoimmune history. Assessment of B-cell follicle architecture and Ig production may play a role in identifying patients with unexplained reactive lymphadenopathy who would benefit from immunologic evaluation.