Alkaptonuria in Russia.

Alkaptonuria is characterized by the accumulation of homogentisic acid (HGA), part of which is excreted in the urine but the excess HGA forms a dark brown ochronotic pigment that deposits in the connective tissue (ochronosis), eventually leading to early-onset severe arthropathy. We analyzed a cohort of 48 Russian AKU families by sequencing all 14 exons (including flanking intronic sequences) of the homogentisate 1,2-dioxygenase gene (HGD) and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. Nine novel likely pathogenic HGD variants were identified, which have not been reported previously in any other country. Recently, Bychkov et al. [1] reported on the variant spectrum in another cohort of 49 Russian AKU patients. Here we summarize complete data from both cohorts that include 82 Russian AKU families. Taken together, 31 different HGD variants were found in these patients, of which 14 are novel and found only in Russia. The most common variant was c.481G>A (p.(Gly161Arg)), present in almost 54% of all AKU alleles.

Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib.

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR. Clinical remission was assessed based on DAS28 score <2.6. Protein concentrations were measured using ELISA. Total RNA isolated from whole blood was used for gene expression analysis using quantitative RT-PCR. All patients were diagnosed with Steinbrocker's radiographic stage II-III at baseline, and most showed erosive arthritis with ACPA and RF positivity. Tofacitinib treatment significantly decreased the disease activity. Upon study completion, seven patients showed remission. Before and after TOFA therapy, a significantly higher expression of succinate dehydrogenase and pyruvate kinase genes was observed in all the examined patients compared to healthy subjects. However, the pre-therapy expression of these genes and corresponding proteins was significantly (p ≤ 0.05) lower in patients who showed remission than in other patients with RA. Moreover, we observed that, during follow-up, patients who developed remission showed an increasing trend in the expression of the examined genes, whereas the others showed some decreases in gene expression, although this was not statistically significant. We concluded that, compared with RA patients maintaining persistent moderate or high disease activity, those with clinical remission following tofacitinib treatment showed a significantly lower baseline expression of genes involved in energy generation.