The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient’s age and duration of psoriasis at several timepoints throughout the observation period.

A b s t r a c tMethotrexate inhibits tetrahydrofolic acid production and influences mitochondrial oxygen uptake and activity of several enzymes in the respiratory chain reactions, which utilize nicotinamide adenine dinucleotide-linked (NAD-linked) substrates. Hyperproliferation of keratinocytes in psoriasis requires oxidative phosphorylation, in which the reduced form of nicotinamide adenine dinucleotide (NADH) is an electron donor. One hypothesis links increased cellular metabolism to the increased NADH/NAD + ratio; as expected, the topical application of NAD + (oxidized form of nicotinamide-adenine dinucleotide) resulted in a clinical improvement of psoriatic lesions in one study. Nevertheless, another report revealed reduced fluorescence of NADH in psoriatic plaques. The biological activity of NADH is not limited only to serving as the electron donor. It was also found to regulate gene transcription.

IntroductionSystemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease characterized by immune system activation, vasculopathy, and collagen accumulation. Despite progressive fibrosis of the vasculature, compensatory angiogenesis is impaired. The cause of the shift towards anti-angiogenesis observed in SSc is unknown. The IL-17 cytokine family participates in the pathogenesis of SSc and angiogenesis.Material and methodsOur study aimed to evaluate levels and find relationships between the levels of proangiogenic cytokines and cytokines from the IL-17 family in 42 SSc subjects and 20 healthy controls. VEGF, PlGF, HGF, TGFβ1, GM-CSF, IL-17A, IL-17B, IL-17E and IL-17F were quantified in the sera of all participants by ELISA sandwich kits.ResultsSignificantly higher mean concentrations of PlGF compared to controls - mean value (19.3 pg/ml in the SSc group vs. 11.4 pg/ml in the control group; p<0.001) and of HGF (1931 pg/ml in the SSc group vs. 1483 pg/ml in controls; p<0.05). Mean serum TGFβ1 level was also significantly lower in the SSc group (781 pg/ml) than controls (35991 pg/ml; p<0.001). Among the IL-17 family, significantly higher mean concentrations of IL-17B (67.0 pg/ml vs. 2.6 pg/ml in controls; p<0,001), IL-17E (8.0 pg/ml vs 0.64 pg/ml in controls; p<0.001) and IL-17F (0.42 pg/ml vs. 0.0 pg/ml in controls; p< 0.01) were detected. Serum concentrations of HGF and PlGF correlated with the concentrations of IL17A, IL-17B, and IL-17E.ConclusionsIn conclusion, our findings indicate that selected cytokines from the IL17 family participate in the pathogenesis of SSc and are responsible for the vascular abnormalities associated with this disorder.

Narrow band (311 nm) UVB phototherapy is established treatment for psoriasis. DNA is a target for UVB via formation of cyclobutane pyrimidine dimers, which trigger loss of dendritic cells and macrophages, and inhibit CD4+ and CD8+ T cells. UV causes the formation of thymine dimers, which activate nuclear enzyme poly(ADP-ribose) polymerase. The fact that poly(ADP-ribose) polymerase utilizes nicotinamide-adenine dinucleotide (NAD) explains NAD decreases after UV irradiation. NADH regulates transcriptional repressor carboxyl-terminal binding protein, whereas NAD(+) is a co-substrate in deacylation reactions, engaged in genomic silencing. Hyperproliferation of psoriatic keratinocytes requires NADH during oxidative phosphorylation. In one study the NADH fluorescence (reflecting NADH amount) was reduced in psoriatic lesions. NAD(+) used topically was as effective as 0.1% anthralin. Spectrophotometry enables real-time measurements of NADH fluorescence in vivo in the epidermis and points out a new direction for application of biophysics in medicine. streszczenie Fototerapia wąskim pasmem UVB (311 nm) jest uznaną metodą leczenia łuszczycy. Molekularnym punktem uchwytu fototerapii UVB jest DNA poprzez tworzenie się dimerów cyklobutanopirymidynowych, które wyzwalają utratę komórek dendrytycznych i makrofagów oraz hamują komórki CD4+ i CD8+. Promieniowanie UV powoduje wytwarzanie dimerów tymidynowych aktywujących jądrową polimerazę poli(ADP-rybozy) (PARP). Zużywanie przez PARP dinukleotydów nikotynoamidoadeninowych (NAD) wyjaśnia zjawisko zmniejszania się zawartości NAD po naświetlaniu UV. NADH reguluje represorowe białko transkrypcji wiążące koniec karboksylowy, natomiast NAD(+) służy jako kosubstrat w reakcjach deacylacji, które mają udział w wyciszaniu genomu. Hiperproliferacja keratynocytów w łuszczycy wymaga zużywania NADH podczas fosforylacji oksydacyjnej. W jednym z badań stwierdzono obniżoną fluorescencję NADH (odzwierciedlającą zawartość NADH) w zmianach łuszczycowych. Stwierdzono, że NAD(+) stosowany miejscowo jest równie skuteczny co 0,1% antralina. Spektrofotometria umożliwia pomiar fluorescencji NADH w naskórku

Neonatal lupus erythematosus (NLE) is a congenital autoimmune condition in which the transplacental passage of immunoglobulin G (IgG) directed against auto-antigens causes clinical symptoms in the foetus or neonate. Anti-Ro/ SS-A, anti-La/SS-B, and to a lesser extent, anti-U1RNP autoantibodies (aAbs) have the strongest association with NLE. However, ~ 50% of affected mothers are asymptomatic despite carrying those aAbs. The clinical picture of the disease is very diverse. Cardiac manifestations are the most severe, including congenital heart block (CHB), with a mortality rate of ~18%. Preventative therapy with hydroxychloroquine (HCQ) reduces the recurrence rate of CHB in subsequent pregnancies by ~50%.