Analysis of key markers: IL-10/sHLA-G in psoriasis patients and the identification of 14-bp INDEL in the HLA-G gene.

BACKGROUND: Psoriasis is a chronic inflammation resulting from interactions between immunological and genetic factors. An important tolerogenic role in this autoimmunological disease is played by HLA-G, which is modulated by IL-10. Therefore, this study (N.=80) aimed to evaluate changes in the serum sHLA-G and IL-10 levels in active psoriasis vulgaris and in the early stages of treatment with Methotrexate (MTX) compared to healthy controls. The 14-bp INDEL of the HLA-G gene was evaluated to find possible associations with clinical and laboratory variables. METHODS: The level of sHLA-G and IL-10 in serum was evaluated (ELISA tests) in patients before the first dose of MTX and at week 12 of treatment, compared to healthy control donors. The 14-bp INDEL in 3'UTR of the HLA-G gene was identified using gDNA templates isolated from full blood. HLA-G amplicons were obtained by PCR, separated by electrophoresis and sequenced. RESULTS: The mean serum IL-10 level was 4.653±3.33 pg/mL in psoriatic patients, 13.3±9.64 pg/mL after short MTX treatment, compared to 6.23 pg/mL in healthy controls. In addition, the serum level of sHLA-G was 0.275±0.03 ng/mL and 0.332±0.06 ng/mL in patients before and after MTX treatment, respectively, and 0.302±0.08 ng/mL in the control group. A correlation was found (r=-0.43; P<0.005) between the IL-10 and BSA serum levels in psoriasis patients after MTX treatment, indicating health improvement. The three genotypes identified in the 3'UTR of the HLA-G revealed no association with sHLA-G level in serum. CONCLUSIONS: The mean levels of sHLA-G and the key anti-inflammatory cytokine IL-10 in the blood of pretreatment psoriasis patients are low and indicate that the immunotolerance mechanisms have failed. Treatment of psoriasis patients with low systemic levels of sHLA-G and IL-10 brings them to the same or higher protein levels, respectively, as in healthy donors. Higher sHLA-G levels in healthy donors and after MTX treatment, compared to the sHLA-G levels in the acute phase of psoriasis, indicates its immune system surveillance function.

Clinicopathologic retrospective analysis of annular pustular psoriasis.

Annular pustular psoriasis (APP) is a rare form of pustular psoriasis with a chronic relapsing course and a good prognosis. The clinical picture is characterized by erythematous lesions, usually polycyclic, with the presence of small, sterile pustules on the circumference of the lesions and fine peeling. We present two cases of APP with diagnostic problems: a 65-year-old woman that suffered from intermittent APP with remission and exacerbation for many years, and an 83-year-old man with lesions that developed after atenolol treatment. In both cases, the patients were thought to have drug provocation, and therefore acute generalized exanthematous pustulosis (AGEP) was diagnosed. Only a thorough analysis of the course of the disease and histopathological examination allowed correct diagnosis. The clinical picture of APP is similar to AGEP, generalized pustular psoriasis (GPP), also known as von Zumbusch pustular psoriasis, and subcorneal pustular disease, and it requires accurate differential diagnosis.

Presence of Chlamydophila pneumoniae DNA in blood cells is a frequent event in patients with the late stage of primary cutaneous lymphomas and with atopic dermatitis.

INTRODUCTION: Microbial infection and associated super antigens have been implicated in the pathogenesis of cutaneous T-cell lymphoma (CTCL), and many patients die from complicating bacterial infections. It has been postulated that Chlamydophila pneumoniae (C. pneumoniae) infection may be involved in the pathogenesis of Mycosis fungoides (MF) but published data are limited and controversial. AIM: To analyze the frequency of (C. pneumoniae) DNA presence in blood samples of lymphoma cases. MATERIAL AND METHODS: Using Q-PCR method we analyzed the presence of DNA in the blood samples obtained from 57 patients with CTCL (55 - mycosis fungoides (MF)/Sézary syndrome (SS), one primary cutaneous anaplastic large cell lymphoma (CD30+) and one NKT cell lymphoma) and 3 patients with cutaneous B-cell lymphomas, and 120 individuals from control groups (40 patients with psoriasis, 40 patients with atopic dermatitis and 40 healthy controls). RESULTS: Chlamydophila pneumoniae DNA was identified in 13 of 55 cases in the MF/SS group (23.6%), in 1 patient with CD30+ large cell lymphoma and in 1 of 3 patients with B-cell lymphoma. The presence of C. pneumoniae was confirmed in 1 of 40 psoriatic patients (2.5%), in 5 of 40 patients with atopic dermatitis (12.5%) and in none of 40 healthy individuals. Presence of C. pneumoniae DNA in MF patients was strongly associated with disease progression; rs = 0.756; p = 0.0123 for groups IA → IVB, and was noted more frequently in advanced (III + IV) stages than in early (I-II) stages (p = 0.0139). There are no differences in the mean age of MF/SS patients with and without infection. CONCLUSIONS: The presence of C. pneumoniae DNA in the blood cells is a frequent event in late stages of MF/SS and may be explained by Th2 shift and suppression of the immune system during the course of the disease.

The effect of subcutaneous methotrexate on markers of metabolic syndrome in psoriatic patients - preliminary report.

INTRODUCTION: Methotrexate (MTX) has anti-proliferative and anti-inflammatory effects in psoriasis. Moreover, low doses can reduce the risk of developing cardiovascular diseases. It turns out that psoriasis and atherosclerosis have a similar pathogenetic mechanism: the same pro-inflammatory cytokines, Th1 and Th17, are involved in both diseases. AIM: To evaluate the effects of metabolic markers, protective cytokines (interleukin 10 (IL-10), transforming growth factor ß (TGF-ß)) and a marker of endothelial damage (endocan) in patients with plaque psoriasis. MATERIAL AND METHODS: The study included 24 patients aged 27-69 years (9 female, 15 male) with plaque psoriasis. The metabolic syndrome according to the International Diabetes Federation (IDF) was evaluated. The laboratory tests were performed under fasting conditions: C-reactive protein (CRP), glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL), uric acid, endocan, IL-10, and TGF-ß. After 12 weeks of treatment with MTX injections 15 mg/week, every patient was assessed with the same laboratory tests. RESULTS: After treatment we observed a statistically significant increase of endocan and IL-10, but no significant differences in the titer of TGF-ß. C-reactive protein was reduced by approximately 54.7%. No improvement of lipid profile was observed, and even a significant increase in triglycerides was noted. Similarly, no significant difference was seen in the case of glucose and uric acid prior to and after treatment. CONCLUSIONS: Methotrexate in low doses in short-term treatment decreases CRP (anti-inflammatory effect) and increases endocan and IL-10 (potential protective role). Methotrexate is characterized by good efficacy and tolerability in therapy of patients with psoriasis.

Frequency of streptococcal upper respiratory tract infections and HLA-Cw*06 allele in 70 patients with guttate psoriasis from northern Poland.

INTRODUCTION: The association of guttate psoriasis with a streptococcal throat infection and HLA-Cw*06 allele is well established in different populations. Nevertheless, only few studies on this form of disease have been performed in the Polish population. AIM: To analyze the frequencies of streptococcal-induced guttate psoriasis and HLA-Cw*06 allele in 70 patients with guttate psoriasis originating from northern Poland. MATERIAL AND METHODS: Seventy patients with guttate psoriasis and 24 healthy volunteers were enrolled into the study. Both groups were sex- and age-matched. The evidence of streptococcal infection was based on the positive throat swabs and/or elevated ASO titers. The modified method, including PCR-SSP and PCR-RFLP, was applied to HLA-Cw*06 genotyping. RESULTS: HLA-Cw*06 allele was confirmed in 49 (70%) out of 70 patients, which is significantly higher than in the control population (30%) (p = 0.001). Evidence for streptococcal infection was found in 34 (48.5%) subjects with psoriasis. Twenty-seven of them (79%) carried HLA-Cw*06 allele. In 36 individuals in whom no evidence of streptococcal infection was found, 14 (39%) did not carry HLA-Cw*06 allele. CONCLUSIONS: Our data confirm that HLA-Cw*06 is a major, but not imperative, genetic determinant for guttate psoriasis.

Oral retinoids and rexinoids in cutaneous T-cell lymphomas.

Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids' action is unclear. It is based on the presence of specific receptors' families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.