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 immunode ciency disease (CVID) have splenomegaly necessitating splenectomy but its consequences on the immunological pro le 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 signi cant peripheral lymphopenia (p=0.001), signi cantly 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 signi cantly 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 ampli cation of the CD8+ T-cell compartment is a CVID characteristic in patients with splenomegaly. Our results highlight this CD8+ ampli cation 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 de ciency, but rather true CVID, as their lymphopenia might suggest lymphocyte trapping in the spleen.

Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion

“…Patients with CVID and splenomegaly usually have peripheral lymphopenia and decreased switched memory B cells. Splenectomy usually restores the absolute circulating lymphocytes, although B cell subpopulations don’t change [ 57 ]. All of this is consistent with the immunophenotype of our patient.…”