Role of chemokine signaling in the pathogenesis of Good's syndrome - a preliminary study.

摘要

Good's syndrome (GS), is a rare coincidence of thymoma and hypogammaglo-bulinemia. It is also marked by a reduction in number (or absence) of B cells. B and T cell deficiency in thymoma patients is sometimes referred to as GS, but it represents rather a different disease with distinct etiology and pathogenesis.The coincidence of involvement of two central immune organs (bone marrow and thymus) may indicate that lymphocyte circulation in GS is defective. In GS the enlargement of thymus and simultaneous atrophy of B-cell compartment in bone marrow direct to the hypothesis that GS may arise due to defective mobilization of common lymphocyte precursors (CLP) to thymus and insufficient homing of cells to bone marrow (BM). Cell migration occurs in response to the relative levels of chemokines, i.e. homing to marrow compartment depends on the increased level of CXCL12 (SDF-1) in the BM. Previous study indicated that low CXCR4 membrane expression on CD34(+) cells characterizes cells with potential to be mobilized to peripheral blood. The same phenomenon may underlay the pathogenesis of GS. In this paper we describe two patients with Good syndrome of mild and high grade, who were tested for expression of CXCR4 (a SDF-1 receptor) on cells in blood and bone marrow. Patient (E.W.) presented with : (i) mild hypogammaglobulinemia, sporadically demanding intravenous immunoglobulin substitution , (ii) low percentage of CD20+ cells in peripheral blood ( 1,4% in lymphocytes population ), and (iii) a thymic enlargement of moderate degree. Patient (E.P.) suffered from: (i) severe hypogammaglobulinemia (IgG approx=60mg/dl), (ii) absence of CD20+ cells in peripheral blood (0.04% lymphocytes), and (iii) severe thymic enlargement. The first patient (E.W.) presented with CXCR4 expression on 82.6% of lymphocytes in BM, the other patient (E.P.) on 46.3%. Interestingly, the bone marrow of patient with severe form of GS (thymic enlargement, E.P.) contained more CD10-positive than BM of the E.W. (11,38% vs. 0.1% cells). CD10 (endopeptidase, enkephalinase), which is capable of cleaving many small molecular weight peptides, may limit activity of chemokines, for example SDF-1. This data indicate that SDF-1 may promote homing of lymphoid precursors to BM, and inhibit migration to the vascular niche as well as migration of CLPs to the thymus. In contrast weak expression of CXCR4 and SDF-1 signal favors vigorous CLP migration to the thymus, and thymoma development (especially predominantly lymphocytic) in Good's syndrome.