In order to understand more clearly the gene transcriptional profiles associated see more with CsA treatment in OS patients, 90 genes related to the immune system were examined by TLDA before and after successful treatment (patient
1). After treatment, 26·6% (24 of 90) of genes showed an expression level of more than twofold increase or decrease compared with the patient’s baseline gene expression (Fig. 4). Of these, the expression of 11 genes (12·2%) was down-regulated (by a factor of 2·3–5·2, values of 0·44–0·19, respectively, in Fig. 4, and 13 genes (14·4%) were up-regulated (by a factor of 2·04–19). The expression of several genes that are known to be down-regulated by CsA therapy such as IL-2 and Fas ligand find more (FasL) were found to be low (0·197- and 0·32-fold decrease). Interestingly, several genes that are known to be involved in immune regulation and autoimmunity were found to be markedly up-regulated
[e.g. IL-10, intercellular adhesion molecule (ICAM) 1 and transforming growth factor (TGF)-β] or down-regulated (e.g. CCR4 and CCR5). The immunological hallmark of OS is the expansion and activation of an oligoclonal population of autoreactive T cells. We have already shown that, in OS, similar T cell expansions are found in peripheral blood and in target organs (e.g. skin) [12]. These cells should be controlled rapidly by immunosuppressive agents to avoid tissue infiltration and to improve the general outcome of OS patients [14]. Here we describe a selective immune response to such treatments in patients with Omenn phenotype. Diverse topical and systemic immunosuppressive
therapies have been shown to be useful in OS patients. Many use CsA as the gold standard treatment for these patients. Alternatively, tacrolimus (FK506) is used. Despite similarity in their accepted mode of action, they alter T cell receptor expression differentially in vivo, therefore can have different effects on OS patients [15]. Failure of treatment Thiamine-diphosphate kinase sometimes requires alternative or a combination of therapies [16]. Herein, we report on two patients; the first patient responded to CsA treatment while the second patient did not. Surprisingly, the initial expanded oligoclonal autoreactive clone (TCR-Vβ 17) in the latter patient responded well to CsA treatment, but other TCR-Vβs had started to expand, probably causing the patient’s unremitting autoimmune symptoms. Many unknown environmental and/or host factors can produce expanded lymphocytes in OS. In some cases the trigger (e.g. infection) that exacerbates the autoreactive process is found [17]. Patient 2 underwent a thorough infectious work-up, which was found to be negative, and no other obvious factor to trigger his symptoms could be detected to explain the presence of new TCR clones. However, expansion of certain new TCR-Vβ clones may also represent not only pathogen exposure, but also skewing towards self-antigens and autoimmunity [9].