Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.     

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

Serum levels of anti‐Fcγ receptor IIB/C antibodies are increased in patients with systemic sclerosis

Systemic sclerosis (SSc) is a systemic autoimmune disorder that results in fibrosis of the skin and multiple internal organs. Although the precise mechanism is unknown, it appears to result from the overproduction of extracellular matrix proteins and aberrant immune activations. Receptors for the Fc region of immunoglobulin (Ig)G (FcγR) are members of the Ig superfamily that modulate both activation and inhibition of immune responses. FcγRIIB is the sole inhibitory member, which has an intrinsic cytoplasmic immunoreceptor tyrosine‐based inhibitory motif. The present study was undertaken to investigate the circulating concentrations of anti‐FcγRIIB/C antibodies (Ab) in patients with SSc. Serum levels of anti‐FcγRIIB/C Ab were significantly increased in patients with SSc compared to those in controls and in patients with localized scleroderma. Serum levels of anti‐FcγRIIB/C Ab in patients with limited cutaneous SSc were similar to those in patients with diffuse cutaneous SSc. Among SSc patients, serum levels of anti‐FcγRIIB/C Ab were increased in those with nail‐fold bleeding and decreased in those with diffuse pigmentation and calcinosis. These findings support the notion that increased serum anti‐FcγRIIB/C Ab levels are involved in aberrant immune responses in SSc.     

Application of the fracture risk assessment tool (FRAX®) and determination of suitable cut-off values during primary screening in specific health check-ups in Japan

Specific health check-ups, which do not include osteoporosis screening, are conducted more frequently than periodic osteoporosis screening in Japan. In this study, we investigated the usefulness of the fracture risk assessment tool (FRAX^®) during specific health check-ups, evaluated the variations in its usefulness for 2 consecutive years, and determined FRAX^® cut-off values for osteoporosis screening. FRAX^® questionnaires were distributed to subjects who underwent specific health check-ups in 2009 and 2010 at Asahi-machi. Subjects who exhibited FRAX^® cut-off values of ≥10 % were advised to be screened at a medical institution. Bone mineral densities (BMDs) were measured in 201 subjects in 2009 and 105 subjects in 2010 after specific health check-ups, and treatment was initiated for 79 subjects in 2009 and 24 subjects in 2010. The number of subjects examined and the rate of treatment initiation following specific health check-ups were higher than those in subjects following periodic osteoporosis screening in 2009. However, the number and the rate following specific health check-ups dropped in 2010. According to receiver operating characteristic curves analyses, the sensitivity and specificity of FRAX^® to determine osteoporosis treatment were highest when the cut-off values were 8 % for men and 10.5 % for women. In conclusion, the combination of FRAX^® and specific health check-ups was more useful than periodic osteoporosis screening to narrow down the subjects and to motivate them to seek follow-up. Cut-off values for specific health check-up using FRAX^® should be approximately 8 % for men and 10.5 % for women