Yuta Araki

Hermansky‐Pudlak syndrome type 4 with a novel mutation

type vitiligo complicated with Ivemark syndrome and hepatitis C. It was evident that the efficacy of excimer light and immune cell infiltration pattern were quite different between non-segmental and segmental lesions, indicating coexistence of different pathological conditions in the case of mixed vitiligo. ACKNOWLEDGMENTS: We thank Kenju Nishida and Eriko Nobuyoshi for their expert technical assistance for immunohistochemistry.

Characterization of melanosomes and melanin in Japanese patients with Hermansky-Pudlak syndrome types 1, 4, 6, and 9

Hermansky–Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition. Most of the causative genes for HPS encode subunits of the biogenesis of lysosome‐related organelles complex (BLOC). In this study, we identified one patient each with HPS4, HPS6, and HPS9 by whole‐exome sequencing. Next, we analyzed hair samples from the three patients and representative patients with HPS1 and controls using electron microscopy and chemical methods. All HPS patients had fewer, smaller, and more immature melanosomes than healthy controls. Further, all patients showed reduced total melanin content and increased levels of benzothiazine‐type pheomelanin. The results of this study demonstrate the impact of the dysfunctions of BLOCs on the maturation of melanosomes and melanin levels and composition through analysis of their hair samples.

Genetic analyses of oculocutaneous albinism types 2 and 4 with eight novel mutations.

Kenji Kabashima* Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan, Singapore Immunology Network (SIgN) and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, IMMUNOS Building #3-4, Biopolis 138648 Singapore, PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan * Corresponding author. Fax: +81 75 761 3002. E-mail addresses: kichu@kuhp.kyoto-u.ac.jp (A. Kitoh), kaba@kuhp.kyoto-u.ac.jp (K. Kabashima).

Spectrophotometer is useful for assessing vitiligo and chemical leukoderma severity by quantifying color difference with surrounding normally pigmented skin.

Acquired skin hypopigmentation has many etiologies, including autoimmune melanocyte destruction, skin aging, inflammation, and chemical exposure. Distinguishing lesions from normally pigmented skin is clinically important to precisely assess disease severity. However, no gold standard assessment method has been reported. We aimed to investigate whether spectrophotometers are useful for assessing vitiligo and rhododendrol (4‐(4‐hydroxyphenol)‐2‐butanol) (Rhododenol®)‐induced leukoderma disease severity by quantifying skin color.

Incontinentia pigmenti with retinal vascular anomaly and deletion of exons 4-10 in NEMO.

plained of blurry vision. Slit-lamp examination showed a mild inflammatory reaction with fibrin formation and posterior synechia in the anterior chamber in both eyes, suggesting mild bilateral acute anterior uveitis (Fig. 1d). Two months thereafter, the size and the number of pre-existing depigmented patches, which were previously diagnosed as vitiligo, had increased (Fig. 1e). Moreover, poliosis and alopecia areata simultaneously emerged (Fig. 1f). The poliosis area gradually expanded so that all the hairs of the scalp, eyebrows and eyelashes became grey (Fig. 1g). No sensorineural hearing loss and no meningoencephalitis were observed. Laboratory data were within normal ranges except mild reduction of thyroid-stimulating hormone levels (0.33 mIU/L; normal range, 0.4–5.1). Human leukocyte antigen (HLA) serotyping and genotyping analysis revealed that the patient had HLA-A11, A31, B62 and B51, and HLA-DRB1*04:10 and HLADRB1*04:06 alleles. A skin biopsy specimen from alopecia lesion in the scalp demonstrated peribulbar lymphocytic infiltration and spillage of melanin granules into the dermal papilla (Fig. 1h). On the basis of these findings, we diagnosed this case as an acute anterior uveitis with VKH-like eruptions induced by nivolumab. The uveitis was mild and could be treated with steroid instillation and mydriatics. As a result of consecutive treatment with nivolumab, the metastatic nodules in the lung remained static for 11 months (Fig. 1c). Nivolumab, a humanized antibody against PD-1, which is an inhibitory molecule involved in T-cell activation, has excellent clinical efficacy against advanced melanoma. Administration of nivolumab overrides the tolerance to self-antigens, resulting in autoimmune thyroiditis, hypophysitis, colitis and pneumonitis. Here, we report a case of acute anterior uveitis and VKH-like eruptions associated with nivolumab therapy. VKH is an autoimmune disorder against a melanocytic antigen including tyrosinase, gp100 and MART-1, and is characterized by uveitis and neurological and cutaneous abnormalities. Uveitis and VKH-like eruptions in this case are thought to be elicited by suppression of the immune inhibitory signal by nivolumab. The uveitis in the present case was confined to the anterior portion of the eyes and was controlled by topical steroid administration, therefore discontinuation of nivolumab therapy was not required. Recently, a case of acute anterior uveitis induced by administration of ipilimumab was reported. VKH is a serious ocular disorder, which can cause irreversible loss of vision; however, the case of uveitis associated with VKH induced by nivolumab may be mild. HLA predisposing to VKH have been identified. Consistent with these findings, our patient carried the HLA-B51 and the DRB1*04:10 allele. Hence, HLA typing could help predict the onset of uveitis and VKH associated with the administration of nivolumab.

Microsatellite polymorphism located immediately upstream of the phosphatidylinositol glycan, class K gene (PIGK) affects its expression, which correlates with tyrosinase activity in human melanocytes

BACKGROUND Glycosylphosphatidylinositol (GPI) acts as a membrane anchor and a post-translational modifier for more than 150 proteins (called GPI-anchored proteins: GPI-APs). However, little study has been done to explore the role of GPI-APs in melanocytes. METHODS The relationship between the mRNA expression of the genes which play essential roles in GPI anchoring system [phosphatidylinositol glycan, class A, and class K gene (PIGA, PIGK)] and melanogenesis-related genes (MITF, TYRP1, TYRP2, and TYR) as well as DOPA oxidase activities were evaluated in 13 different normal human epidermal melanocytes (NHEMs). A short tandem repeat (STR) polymorphism located in the predicted promoter region of PIGK was genotyped in the NHEMs. RNA interference experiment of PIGK was also conducted using one of the NHEMs. RESULTS PIGK mRNA expression in NHEMs were strongly in inverse correlation with TYR mRNA and DOPA oxidase activities. NHEMs with the STR polymorphism revealed a low level of PIGK expression. However, a transient knockdown of PIGK in NHEM failed to reveal significant changes in the expression of TYR mRNA and DOPA oxidase activity. CONCLUSIONS This report firstly demonstrated that inadequate protein-GPI anchoring caused by suppression of PIGK might affect the expression or function of some GPI-APs associated with tyrosinase activity.