Abstract
Good’s syndrome (GS), is a rare condition defined as a coexistence of thymoma and hipogammaglobulinaemia. Involvement of central lymphoid organ prompts concept about perturbation in lymphocyte migration and differentiation. Cell homing to bone marrow compartment depends on the CXCR4↔CXCL12 interaction. In this paper we describe two patients with GS-mild and severe form, presenting differences in the expression of CXCR4 on cells in peripheral blood and bone marrow. Patient 1 (mild form): (i) Mild hipogammaglobulinaemia (IgG=150 mg/dL), (ii) Low count of peripheral B cells (14%, 60 cells/μL) and NK (18%, 77cells/μL); high level of T cells (93.3%, 4006 cells/ μL), (iii) Moderate thymic enlargement (9 × 15 cm), (iv) CXCR4 expression in BM 82.6% (20139/μL), 34% CXCR4+CD19+ (8289/μL). Patient 2 (severe form): (i) Severe hipogammaglobulinaemia (IgG=20 mg/dL), (ii) Absence of B and NK cells deficiency (in peripheral blood 0.4% i.e., 10/μL, and 6.17%-47.3/μL respectively), (iii) Severe thymic enlargement (20 × 25 cm) (iv) CXCR4 expression in BM 46.3% (552/μL); 6.1%, CXCR4+CD19+ (174/ μL). Interestingly, the bone marrow of patient with severe form of GS contained more CD10-positive B cells than BM of the patient with mild form (80% vs. 5.88% of B cells), but in former as well as letter a significant proportion of the total CXCR4-positive lymphocytes are negative for B cells marker (comparable: 48.1% and 53.1% respectively). In our patients a tenfold decrease in the CD4-positive γδ T cells (CD4+TCRγδ) counts was observed. Both cases went up fatal due to progression of nasopharyngeal cancer (mild form) and breast cancer (severe form). This data confirm that earliest B cell precursors, pre-pro-B cells and end-stage B cells, plasma cells require CXCR4 ↔ CXCL12 interaction. In contrast in GS weak expression of CXCR4 in marrow precursors is source of B cell differentiation arrest on pro-B cell stage. The low level Nk and CD4+γδ T cells in Good syndrome is the new observation.
Highlights
The association between presence of a thymoma and hipogammaglobulinaemia was for the first time described in 1954 by Dr Robert Good who described a case of the rare immunodeficiency [1]
The cause and pathogenesis of this disorder are still unknown, there are some evidences that the basic defects are bone marrow derived (BM) [6,7]
Coexistence of humoral and cellular deficiency, presence of thymoma in the context of observed bone marrow abnormalities prompted us to hypothesis that impaired migration of common lymphoid precursor (CLP) and further education may be a part of Good syndrome (GS) pathogenesis
Summary
The association between presence of a thymoma and hipogammaglobulinaemia was for the first time described in 1954 by Dr Robert Good who described a case of the rare immunodeficiency [1]. T-cell and thymic abnormalities in GS are poorly described; much of the literature is devoted to thymoma prognostic classification, its association with autoimmune diseases, paraneoplastic syndromes and secondary malignancy [3,4,5]. The cause and pathogenesis of this disorder are still unknown, there are some evidences that the basic defects are bone marrow derived (BM) [6,7]. Coexistence of humoral and cellular deficiency, presence of thymoma in the context of observed bone marrow abnormalities prompted us to hypothesis that impaired migration of common lymphoid precursor (CLP) and further education may be a part of GS pathogenesis
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