Influence of Splenomegaly and Splenectomy on the Immune-Cell Profile of Patients with Common Variable Immunodeficiency Disease

Abstract Purpose About 25% of patients with common variable immunodeficiency disease (CVID) have splenomegaly necessitating splenectomy but its consequences on the immunological profile of CVID patients have never been studied. We analyzed 11 CVID patients’ comprehensive blood immune-cell phenotypes before and after splenectomy. Methods Flow-cytometry analyses of immune-cell populations. Results Among 89 CVID-cohort patients, 41 with splenomegaly, splenomegaly was strongly associated with granulomatous disease, autoimmune disorders, lymphoid hyperplasia and portal hypertension. CVID patients with splenomegaly have significant peripheral lymphopenia (p=0.001), significantly fewer peripheral class-switched memory B cells (smBs) (p=0.001), CD4+ T lymphocytes (p=0.001), NK (p=0.0001) and dendritic cells (p≤0.01), and significantly more circulating CD4+ and CD8+ (p=0.00001) T-cell-subset activation (p=0.00005), than CVID patients without splenomegaly. Examination of splenectomy impact on circulating lymphocyte-subset distributions demonstrated the drastically enhanced total circulating-lymphocyte count post-splenectomy, predominantly B lymphocytes and CD8+ T cells. However, splenectomy did not change B-cell distribution, with smBs remaining persistently low, in contrast to complete inversion of the circulating T-cell composition, with reversal of the CD4+/CD8+ ratio suggesting that amplification of the CD8+ T-cell compartment is a CVID characteristic in patients with splenomegaly. Our results highlight this CD8+ amplification in splenomegaly–CVID patients which might be explained by a homing effect to the spleen and/or possible chronic virus replication, which in turn could induce T-cell expansions. Conclusion CVID patients with lymphopenia and splenomegaly should not be thought to have combined immune deficiency, but rather true CVID, as their lymphopenia might suggest lymphocyte trapping in the spleen.