Primary immunodeficiencies and the rheumatologist.
Primary immunodeficiencies and the rheumatologist.
复制标题
原发性免疫缺陷和风湿病学家。
DOI：
10.1097/00002281-200307000-00007
复制
发表时间：
2003
影响因子：
5.1
通讯作者：
Candotti,Fabio
中科院分区：
文献类型：
--
作者：
O'Shea,JohnJ;Holland,Steven;Candotti,Fabio
Primary immunodeficiency disorders are a heterogeneous collection of genetic disorders manifested by impaired host defense mechanisms associated with an increased incidence of infection. In addition, many immunodeficiencies are also associated with an increased susceptibility to malignancy. Though these disorders were first classified by their clinical and/or immunologic presentation, enormous advances have been made in the molecular understanding of these disorders that have induced more recent efforts to order these diseases by their pathophysiological basis [1, 2]. Of the nearly 100 recognized primary immunodeficiencies, the genetic basis of more than three quarters has been elucidated. These disorders are summarized in Table 1. But why should this topic be of interest to rheumatologists? If asked to compare primary immunodeficiencies and autoimmune disorders, the average medically sophisticated individual is likely to come up with a scheme that could be diagrammed in Figure 1A. In essence, the two diseases might be viewed as being at the opposite ends of a spectrum, with primary immunodeficiencies the result of inadequate responses versus autoimmune disorders the consequence of exaggerated immune responses. Autoimmune disorders are associated with the loss of self/nonself and are characterized by seemingly spontaneous lymphocyte activation in the absence of overt infection. While this picture might appear to contrast with diseases in which immune responses to pathogens is impaired, the reality is much more complex than the simplistic “seesaw” view of immune disorders. And in fact, it has been appreciated for some time [3] that a more accurate depiction would be the overlapping Venn diagrams shown in Figure 1B, which is intended to convey the related nature of these disorders (we will refer to this as the “kaleidoscope model”). Clearly, acquired immunodeficiency such as that associated with human immunodeficiency virus is a good example of which autoimmunity is seemingly paradoxically associated with immunodeficiency [4]. As is well appreciated, these patients have autoimmune problems ranging from arthropathies to vasculitis and a lupus-like syndrome. Similarly, arthritis is a common problem in patients with hypogammaglobulinemia. Such patients may also have polymyositis and dermatomyositis. It would therefore not be surprising if as our understanding of primary immunodeficiencies expands, the overlap with autoimmune disease would also likely expand, hence our usage of the kaleidoscope image. For completeness, the autoinflammatory disorders [5] are also included in this scheme, as we expect that the boundaries among these three types of disorders may be indistinct. As will become clear in the following reviews, rheumatologists need to be cognizant of these disorders when assessing their patients because of the clear overlap among these diseases. It is not practical to review all of these diseases in this series, so we have selected a few that we thought would convey the important points.There is a second reason for rheumatologists to consider primary immunodeficiencies, and this pertains to genetics. A general view is that the common autoimmune diseases are complex genetic disorders, meaning that they are not inherited in a simple Mendelian manner. Presumably, these disorders are polygenic with incomplete penetrance, with environmental and hormonal factors also playing a large role. In contrast, many of the primary immunodeficiencies are comparatively simple genetic disorders. From the point of view of molecular pathogenesis of immunologic disease, primary immunodeficiency …
