Psoriasis is an immune-mediated disease where the IL-23/Th17 axis as well as TNF comprise main targets of biological therapy. Immune profiling has so far not been embraced as a clinical tool. We aimed to investigate relationships between individual serum cytokine levels in 40 psoriasis patients before and after receiving biological therapy and Psoriasis Area and Severity Index (PASI) and Dermatological Life Quality Index (DLQI). Serum concentration of 25 cytokines was determined by Luminex technology. Mean PASI and DLQI decreased by 71% and 65%, respectively. Increase of IL-2 positively correlated with improvement of PASI and DLQI. Moreover, increase of IL-5, IL-10, IL-12, IL-22 and GM-CSF correlated with treatment effect. Notably, logistic regression revealed four times higher risk of having severe psoriasis when IL-17A increased by 1 pg/mL (OR: 4.06, P < 0.05). Selected serum cytokines might constitute useful biomarkers for monitoring disease activity and optimizing therapeutic strategies in psoriasis patients.
MRL-lpr mice and the congenic strain MRL þ/þ exhibit pathological abnormalities in the salivary glands similar to Sjögren's syndrome in humans. The lpr genotype has been identified as a mutation in the gene encoding Fas which is a cell surface protein that mediates apoptosis. The mutation is leaky, allowing for low levels of the APO-1/Fas (CD95) receptor and partial activity of Fas/Fas ligand-mediated programmed cell death in this strain. To examine the expression of Fas in situ, the authors analysed thymus, lymph node and salivary gland tissue from BALB/c, MRL þ/þ and MRL-lpr mice by an immunohistochemical technique (ABC-immunoperoxidase) using an anti-Fas (Jo2) antibody. For detection of apoptotic cells the authors used the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling (TUNEL) method. Thymus from MRL þ/þ and normal BALB/c mice showed a higher frequency of Fas expression than was seen in the lpr mice, but the þ/þ mice had similar expression of Fas in lymph nodes as lpr mice. The Fas protein was detected among infiltrating mononuclear cells in the salivary glands of both lpr and þ/þ mice. Apoptotic cells were found in the thymus with similar frequency in all three strains, while in the lymph nodes only BALB/c mice showed apoptosis. There was no, or very low, frequency of apoptosis among infiltrating mononuclear cells in salivary glands of both MRL strains. In conclusion, despite mutation of the Fas gene in the MRL-lpr strain, there was nevertheless an expression of the apoptosis-related Fas protein in lymphoid tissue and salivary glands of these mice. Based on analysis of apoptotic activity, the impaired Fas in autoimmune MRL mice seems to affect primarily the peripheral organs.
Calprotectin showed the strongest correlation with measures of disease activity and may be better than S100A12 when evaluating disease activity in RA patients. More extensive studies are needed to further compare the predictive value of the S100 proteins relative to radiographic progression.
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