Linda Hammond

Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept.

Hereditary periodic fever syndromes comprise a group of distinct disease entities linked by the defining feature of recurrent febrile episodes. Hyper IgD with periodic fever syndrome (HIDS) is caused by mutations in the mevalonate kinase (MVK) gene. The mechanisms by which defects in the MVK gene cause febrile episodes are unclear and there is no uniformly effective treatment. Mutations of the TNFRSF1A gene may also cause periodic fever syndrome (TRAPS). Treatment with the TNFR‐Fc fusion protein, etanercept, is effective in some patients with TRAPS, but its clinical usefulness in HIDS has not been reported. We describe a 3‐year‐old boy in whom genetic screening revealed a rare combination of two MVK mutations producing clinical HIDS as well as a TNFRSF1A P46L variant present in about 1% of the population. In vitro functional assays demonstrated reduced receptor shedding in probands monocytes. The proband therefore appears to have a novel clinical entity combining Hyper IgD syndrome with defective TNFRSF1A homeostasis, which is partially responsive to etanercept.

Suppression of HLA class II expression on thyrocytes by interferon-alpha 1.

Inappropriate expression of HLA class II molecules by human thyroid epithelial cells (thyrocytes) is commonly associated with autoimmune thyroid disease. HLA class 11 expression can be modulated in thyrocytes in vitro by a variety of substances: in particular, it is readily induced by interferon‐gamma (IFN‐γ). Here we show that recombinant IFN‐α1 (rIFN‐α1) does not induce HLA class II expression by thyrocytes. but rather it suppresses the induction of such expression by rIFN‐γ. Similar effects were observed with IFN‐α derived from a lymphoblastoid cell line. The effect of rIFN‐α1 on thyrocytes differs from its effect on human monocytes, reported by others, in which it was found to enhance the expression of HLA class II. Thus, rIFN‐α1 appears to have a differential effect on HLA class II expression, depending on the cell type involved.

Methods for detecting apoptosis in thyroid diseases.

Over the last few years, the importance of apoptosis in determining the fate of thyrocytes in autoimmune thyroid disease has been the topic of intense investigation. It is now clear that thyrocytes from patients with Hashimotos thyroiditis are destroyed as a result of an apoptotic process. However, there is no general consensus on whether the intrathyroidal lymphocytes or the thyrocytes themselves are responsible for their death. The use of a wide range of techniques has contributed to the assessment of this process both in situ on thyroid sections and in vitro on thyroid cell preparations. The apoptosis field of research is rapidly evolving and as the pathways to cell death become unravelled, novel methods will emerge. As each technique offers some advantage, it is critical to know the most suitable method for a specific study. Equally, each method also has intrinsic limitations. Thus, to achieve reliable results, it is necessary to use more than one technique per study. In addition, techniques related to the measurement of the expression of pro-apoptotic and anti-apoptotic genes have been contributing to the study of the susceptibility of the cells to apoptosis and/or to their ability to kill themselves or neighbouring cells. In this review we will focus on the most relevant techniques.