The TTTT B lymphocyte stimulator promoter haplotype is associated with good response to rituximab therapy in seropositive rheumatoid arthritis resistant to tumor necrosis factor blockers

Objective

To investigate the polymorphisms in the promoter region of the B lymphocyte stimulator (BLyS) gene as markers of response to rituximab (RTX) in rheumatoid arthritis (RA).

Methods

The study was first conducted in 152 Italian RA patients and then replicated in an additional 117 RA patients (73 Italian, 44 British). The European League Against Rheumatism response criteria were used to evaluate the response rate at months 4 and 6 after the first cycle of RTX, by means of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate; patients were classified according to the best response shown between months 4 and 6. BLyS promoter polymorphisms were analyzed by polymerase chain reaction followed by the analysis of the restriction fragments, BLyS promoter haplotypes were analyzed using the expectation‐maximization algorithm, and BLyS serum levels were analyzed using enzyme‐linked immunosorbent assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).

Results

The TTTT BLyS promoter haplotype appeared to be significantly associated with response to RTX only in the subset of seropositive patients (those positive for rheumatoid factor and/or anti–cyclic citrullinated peptide). The replication study confirmed that this association was limited to seropositive RA patients in whom treatment with anti–tumor necrosis factor (anti‐TNF) agents had previously failed. In the whole series of seropositive patients in whom anti‐TNF agents had previously failed, patients carrying the TTTT BLyS promoter haplotype were more prevalent in good responders (18 of 43 [41.9%]) than in moderate responders (20 of 83 [24.1%]) or in nonresponders (1 of 21 [4.8%]) (for good responders versus nonresponders, OR 14.4 [95% CI 1.77–117.39], P = 0.0028). Furthermore, multivariate analysis selected the TTTT BLyS promoter haplotype as an independent marker of good response to RTX (for good responders versus nonresponders, OR 16.2 [95% CI 1.7–152.5], P = 0.01; for good responders versus moderate responders and nonresponders combined, OR 3.1 [95% CI 1.2–7.8], P = 0.02). The relationship between BLyS polymorphisms and BLyS serum levels remained unclear.

Conclusion

BLyS promoter genotyping may be suitable for identifying seropositive RA patients who may have a good response to RTX after anti‐TNF agents have failed.

     

Two pathogen reduction technologies—methylene blue plus light and shortwave ultraviolet light—effectively inactivate hepatitis C virus in blood products

BACKGROUND: Contamination of blood products with hepatitis C virus (HCV) can cause infections resulting in acute and chronic liver diseases. Pathogen reduction methods such as photodynamic treatment with methylene blue (MB) plus visible light as well as irradiation with shortwave ultraviolet (UVC) light were developed to inactivate viruses and other pathogens in plasma and platelet concentrates (PCs), respectively. So far, their inactivation capacities for HCV have only been tested in inactivation studies using model viruses for HCV. Recently, a HCV infection system for the propagation of infectious HCV in cell culture was developed. STUDY DESIGN AND METHODS: Inactivation studies were performed with cell culture–derived HCV and bovine viral diarrhea virus (BVDV), a model for HCV. Plasma units or PCs were spiked with high titers of cell culture–grown viruses. After treatment of the blood units with MB plus light (Theraflex MB‐Plasma system, MacoPharma) or UVC (Theraflex UV‐Platelets system, MacoPharma), residual viral infectivity was assessed using sensitive cell culture systems. RESULTS: HCV was sensitive to inactivation by both pathogen reduction procedures. HCV in plasma was efficiently inactivated by MB plus light below the detection limit already by 1/12 of the full light dose. HCV in PCs was inactivated by UVC irradiation with a reduction factor of more than 5 log. BVDV was less sensitive to the two pathogen reduction methods. CONCLUSIONS: Functional assays with human HCV offer an efficient tool to directly assess the inactivation capacity of pathogen reduction procedures. Pathogen reduction technologies such as MB plus light treatment and UVC irradiation have the potential to significantly reduce transfusion‐transmitted HCV infections.     

Glycated albumin as a glycaemic marker in patients with advanced chronic kidney disease and anaemia: a preliminary report

Abstract

Background: The association between glycated albumin (GA) and glycaemic status has not been fully described in patients with advanced chronic kidney disease (CKD) in relation to anaemia. The aim of this study was to evaluate the relationship between GA and fasting plasma glucose (FPG) and HbA1c in patients with advanced CKD and to evaluate the influence of anaemia in such relationship.

Materials and methods: Patients with CKD stage 4 or 5 were included in the study. eGFR was calculated by the CKD-EPI creatinine equation. Plasma GA was measured by an enzymatic method.

Results: Eighty-one patients were included in the study, 46 (57%) were males; the mean age was 67?±?14?years. HbA1c was correlated with Hb (r?=?0.39; p?=?.0003), and no significant correlation was detected between plasma GA and serum albumin (p?=?.82). A significant association between FPG and GA (r²?=?0.41; p?r²?=?0.42; p?r²?=?0.55; p?Conclusions: GA, alone or in combination with other biomarkers, can be considered for the evaluation of glycaemic status in patients with advanced CKD and severe anaemia.     

Anxious Self-Statements in Clinic-Referred U.S. and Norwegian Anxiety-Disordered Youth

Examined the relationship between negative self-statements and symptoms of anxiety, depression, and attention-deficit/hyperactivity and functional impairment in two studies of anxiety-disordered youth. Study 1 included 144 anxiety-disordered youth (7–13 years; 54.9 % male) from a university-based research clinic in the USA. Study 2 included 111 treatment-seeking youth (7–13 years; 58.6 % male) from Norwegian community clinics. Results from both studies indicated that total negative self-statements were associated with increased symptoms of anxiety and depression as per child-report. Content specific associations were observed for child-reported symptoms of anxiety but not depression. Associations between child-reported negative self-statements and mother-reported symptoms were mixed. In Study 1, total negative and anxious self-statements were associated with greater functional impairment. The role of negative self-statements in youth’s internalizing symptomatology and the clinical implications are discussed.     

Changes in retinal blood flow after application of topical dipivefrine 0.1 %

Hintergrund: Viele der antiglaukomat?sen Medikamente beeinflussen den okul?ren Blutflu?. Die Blutflu?ver?nderungen in der vorderen Uvea sind in der Literatur beschrieben. über den Effekt von Antiglaukomatosa auf den Blutflu? des hinteren Augenpols wird in neuerer Zeit vermehrt berichtet. Wir pr?sentieren eine Placebo-kontrollierte Studie mit Blick auf den kurz- und mittelfristigen Einflu? von topisch appliziertem Dipivefrin 0,1 % auf den retinalen und papill?ren Blutflu?.     

Serum levels of 25‐hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism

Aim: To analyse serum levels of 25‐hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development. Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring. Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25‐hydroxyvitamin D compared with Swedish mothers. The difference of 25‐hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant. Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.