Background: For severe forms of psoriasis vulgaris, the antipsoriatic fumaric acid esters (FAE) therapy has recently gained increasing acceptance and importance. Until today, there is little knowledge about the mode of action of FAE. However, some evidence exists indicating immunosuppressive effects. Objective: The aim of this study was to examine the systemic, particularly the immunological changes in patients suffering from psoriasis treated with FAE over a long period of time, since we expect to see pharmacological effects of FAE at this point. Methods: This study is based on continuously recorded clinical data and laboratory parameters of 10 patients, who were treated over a period of 12 months with FAE. A quantitative analysis of lymphocytes and their subtypes was carried out by means of flowcytometric methods. Results: 3 months after starting treatment with FAE, a clinical effect with a remission index >95% was achieved in all 10 patients examined. This remained constant until the end of this study. Focusing on leukopenia, and particulary on lymphopenia as important parameters, these effects were found in all patients. The lymphocyte subpopulations data demonstrated extensive proportionate reductions. Within the T cell fraction a stronger suppression of CD8⁺ lymphocytes was observed. Conclusion: Our investigations of systemic effects of fumaric acid esters demonstrate the suppressive character of this medication. Effects of cell count reduction in leukocyte and lymphocyte numbers over the entire period of 12 months could be observed. The lymphocytic cell count number is obviously linked to the clinical effect.

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Thyroid dysfunction is more common in human immunodeficiency virus (HIV) patients. But the effects of highly active antiretroviral therapy (HAART) and hepatitis B/C virus (HBV/HCV) coinfection on thyroid function is unclear. We retrospectively reviewed the data of 178 HIV patients and determined the prevalence of thyroid dysfunction and the relationship between thyroid hormone levels, CD4 cell count, HIV-1 duration, HAART duration/regimens, and HBV/HCV coinfection. Of the 178 patients, 59 (33.1%) had thyroid dysfunction, mostly hypothyroidism. Thyroid dysfunction was significantly more frequent in the HAART group (41/104, 39.4%) than in the HAART-naïve group (18/74, 24.3%; P < 0.05). The mean CD4 cell count was significantly lower in patients with hypothyroidism (372 ± 331/μL) than in the other patients (P < 0.05). The FT4 level was significantly lower in the HAART group than in the HAART-naïve group (1.09 ± 0.23 versus 1.20 ± 0.29 pg/mL, P < 0.05). FT3/FT4 levels were negatively related to HIV duration and FT3 levels were positively related to CD4 cell (P < 0.05). HBV patients had lower FT3 levels, while HCV patients had higher FT3 and FT4 levels (P < 0.05). Thyroid dysfunction is more common in HIV patients on HAART, mainly manifested as hypothyroidism. FT3/FT4 levels are correlated with HIV progression. HBV/HCV coinfection increases the probability of thyroid dysfunction.

Mitochondrial dysfunction has been implicated in the pathogenesis of Huntington disease (HD), a primarily neurodegenerative disorder that results from an expansion in the polymorphic trinucleotide CAG tract in the HD gene. In order to evaluate whether mitochondrial DNA (mtDNA) variation contributes to HD phenotype we genotyped 13 single nucleotide polymorphisms (SNPs) that define the major European mtDNA haplogroups in 404 HD patients. Genotype-dependent functional effects on intracellular ATP concentrations were assessed in peripheral leukocytes. In patients carrying the most common haplogroup H (48.3%), we demonstrate a significantly lower age at onset (AO). In combination with PGC-1 alpha genotypes, 3.8% additional residual variance in HD AO can be explained. Intracellular ATP concentrations in HD patients carrying the cytochrome c oxidase subunit I (CO1) 7028C allele defining haplogroup H were significantly higher in comparison to non-H individuals (mean +/- SEM, 599 +/- 51.8 ng/ml, n = 14 vs. 457.5 +/- 40.4 ng/ml, p = 0.03, n = 9). In contrast, ATP concentrations in cells of HD patients independent from mtDNA haplogroup showed no significant differences in comparison to matched healthy controls. Our data suggest that an evolutionarily advantageous mitochondrial haplogroup is associated with functional mitochondrial alterations and may modify disease phenotype in the context of neurodegenerative conditions such as HD.