Immune function in patients with Shwachman-Diamond syndrome
Immune function in patients with Shwachman-Diamond syndrome
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DOI：
10.1046/j.1365-2141.2001.02996.x
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发表时间：
2001-09-01
影响因子：
6.5
通讯作者：
Freedman, MH
中科院分区：
文献类型：
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作者：
Dror, Y;Ginzberg, H;Freedman, MH
Shwachman-Diamond综合征（SDS）是一种遗传性多系统疾病，以外分泌胰腺功能障碍和不同程度的细胞减少为特征。此外，还注意到各种免疫异常。为了阐明SDS患者的免疫能力或免疫功能不全问题，我们对11例SDS患者的免疫功能进行了前瞻性研究。7例复发性细菌感染，6例复发性病毒感染。不同程度的损伤很容易识别。所有患者均有中性粒细胞减少症；然而，除了一名患者外，所有患者的总淋巴细胞计数均正常。9例患者有B细胞缺陷，包括以下一种或多种异常：低IgG或IgG亚类，低循环B淋巴细胞百分比，体外B淋巴细胞增殖减少和缺乏特异性抗体产生。研究的9名患者中有7名至少有一种T细胞异常，包括低百分比的总循环T淋巴细胞或CD3(+)/CD4（+）细胞亚群或体外T淋巴细胞增殖减少。在研究的6名患者中，有5名循环的自然杀伤细胞百分比下降。此外，在所有研究的患者中，中性粒细胞趋化性明显较低。这些数据表明SDS中的主要免疫缺陷成分使患者感染风险增加，即使中性粒细胞数量具有保护作用。这一发现大大拓宽了该综合征的定义：它表明SDS骨髓缺陷发生在早期的血液淋巴细胞干细胞水平上，或者骨髓和胸腺基质的联合缺陷导致了造血和淋巴细胞谱系的异常功能。
Shwachman-Diamond syndrome (SDS) is an inherited multisystem disorder characterized by exocrine pancreatic dysfunction and varying degrees of cytopenia. In addition, various immunological abnormalities have been noted. To clarify the issue of immunological competence or incompetence in SDS, we prospectively studied immune function in 11 patients with SDS. Seven suffered from recurrent bacterial infections and six from recurrent viral infections. Varying degrees of impairment were readily identified. All patients had neutropenia; total lymphocyte counts, however, were normal in all except one patient. Nine patients had B-cell defects comprising one or more of the following abnormalities: low IgG or IgG subclasses, low percentage of circulating B lymphocytes, decreased in vitro B-lymphocyte proliferation and a lack of specific antibody production. Seven out of nine patients studied had at least one T-cell abnormality comprising a low percentage of total circulating T lymphocytes or CD3(+)/CD4(+) cell subpopulations or decreased in vitro T-lymphocyte proliferation. Five out of six patients studied had decreased percentages of circulating natural killer cells. Moreover, neutrophil chemotaxis was significantly low in all the patients studied. These data point to a major immunodeficiency component in SDS that places patients at heightened risk of infections, even if neutrophil numbers are protective. This finding broadens the definition of the syndrome substantially: it suggests that the SDS marrow defect occurs at the level of an early haematological-lymphocytic stem cell or that a combined marrow and thymic stromal defect accounts for the aberrant function of haematopoietic and lymphopoietic lineages.