Spleen Histologic Appearance in Common Variable Immunodeficiency

Abstract

Histologic and phenotypic analyses of splenectomy samples from 17 patients with common variable immunodeficiency (CVID) showed the following nonspecific, evocative, white-pulp lesions: white-pulp hyperplasia (WPH) with reactive follicles, giant follicles (GFs), marginal zone hyperplasia, periarteriolar T-zone hyperplasia (PATH) and/or granulomas, which enabled us to discern 2 groups: the first (n=6) composed of WPH with reactive follicles without granulomas, and the second (n=9) characterized by the presence of granulomas with or without WPH. All specimens were Epstein-Barr virus negative by in situ hybridization. Molecular analyses revealed a polyclonal immunoglobulin heavy chain gene (IGH) rearrangement (n=12). WPH-only patients were mostly female individuals and younger at CVID onset, diagnosis, and splenectomy, but their interval between the first symptom and diagnosis was longer; they had more associated infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia; their IgG, IgA, and IgM concentrations were also higher. Granuloma-group patients were mostly male individuals; were older at CVID onset, diagnosis, and splenectomy; had disseminated granulomatous disease, but infectious events, autoimmune disease, pulmonary complications, and liver regenerative nodular hyperplasia were less common; their immunoglobulin concentrations were lower. Histologic comparisons between the WPH-only and granuloma groups showed more intense WPH and more intense marginal zone hyperplasia and fewer GFs in the former versus more developed PATH and more common GFs in the latter. The results of this novel comparative study of the histologic patterns of 17 CVID patients' evocative splenic lesions suggested different biological and clinical profiles.

Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells

“…Examination of the spleen biopsy sample of a pRD patient (P5) confirmed white pulp hyperplasia and the presence of previously described non-necrotic epithelioid granulomas 35 , revealed remarkable reactive and giant follicles, marginal zone hyperplasia and periarteriolar T-zone hyperplasia, which scored high (12) in comparison to what observed in a previous cohort with common variable immunodeficiency and splenectomy 36 (Extended Data Fig. 5a,b ).…”

Lymphoid malignancy in common variable immunodeficiency in a single‐center cohort

“…CVID subjects with autoimmunity may have lymph nodes with particularly irregularly shaped and hyperplastic germinal centers 54 . The spleen in CVID may also show nonspecific, white‐pulp hyperplasia with reactive follicles, giant follicles, marginal zone hyperplasia, and clustered histiocytes in variously formed granulomata 55,56 . Four of the six misdiagnosed subjects had granulomatous infiltrations in organs and or lymph nodes, suggesting that this adds further complexity to these histologic features.…”

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

“…For the 10 splenectomized-CVID patients from the DEFI cohort, immunological data were obtained as described previously and were available only post-splenectomy [13].…”