Noriko Arase

Vitiligo is a common depigmentation disorder characterized by patchy white macules. It has been reported that vitiligo lesions, particularly in exposed areas, such as the face and hands, cause severe psychological distress. Although the classification and outcome of facial vitiligo have been proposed, clinical analyses featuring hand vitiligo are very limited, irrespective of its severe psychological impact. In this study, we investigated hand lesions in nonsegmental vitiligo patients and found that the distribution of hand vitiligo was symmetric, whereas the dominant hand was more frequently affected. Moreover, our clustering analysis newly classified hand vitiligo lesions into four distinct subtypes (n = 140): focal/scattered (46.4%), distal digit (31.4%), universal (12.9%), and proximal digit (9.2%) and their clinical characteristics. The focal/scattered type is the most common subtype and exhibits a distinctive prevalence in pediatric cases. The distal digit type was suggested to be associated with smoking or the Koebner phenomenon. The universal type is a distinct subtype, with onset in older age and a poor response to treatment. The proximal digit type is the rarest subtype, with onset at a young age. In conclusion, these findings deepen our understanding of the heterogeneity of hand vitiligo and support the development of personalized treatment strategies.

Background: Anti-alpha 6 beta 4 integrin autoantibodies can be observed in some patients with mucous membrane pemphigoid. We have previously identified anti-alpha 6 beta 4 integrin extracellular domain autoantibodies together with anti-BP180 NC16A antibodies in a patient with DPP-4 inhibitor-induced bullous pemphigoid. However, the significance and impact of anti-alpha 6 beta 4 integrin antibodies are unknown.Objectives: To characterize anti-alpha 6 beta 4 integrin extracellular domain autoantibodies in pemphigoid patients, to determine whether these antibodies inhibit laminin-alpha 6 beta 4 integrin binding and to observe their systemic effects.Methods: Anti-alpha 6 beta 4 integrin autoantibodies were analysed by staining cells expressing the extracellular region of alpha 6 beta 4 integrin with sera from 20 patients with pemphigoid. The anti-alpha 6 beta 4 integrin autoantibodies were characterized using different transfectants. The binding of laminins to alpha 6 beta 4 integrin was studied using cells expressing the activated conformation of alpha 6 beta 4 integrin and the inhibitory effect of the autoantibodies on the binding of laminins to alpha 6 beta 4 integrin was tested. Trends in antibody titres and clinical symptoms were quantified and analysed.Results: IgG autoantibodies against the extracellular domain of anti-alpha 6 beta 4 integrin were found in some patients with pemphigoid. Laminin binding to alpha 6 beta 4 integrin was observed in the active conformation of alpha 6 beta 4 integrin, and serum from a patient with a high titre of anti-alpha 6 beta 4 integrin antibodies inhibited the binding of both laminin-511 and laminin-332 to alpha 6 beta 4 integrin. alpha 6 beta 4 integrin is expressed on the basement membrane of both skin and small intestine, and exfoliation was observed in the patient's epidermis and small intestinal epithelium. A reduction in the titre of the anti-alpha 6 beta 4 integrin antibody was associated with improvement in both skin and gastrointestinal symptoms.Conclusions: This study demonstrated the presence of anti-alpha 6 beta 4 integrin extracellular domain-specific autoantibodies in some patients with pemphigoid. In addition, these autoantibodies showed inhibitory activity on alpha 6 beta 4 integrin-laminin binding. Anti-alpha 6 beta 4 integrin antibodies can affect the gastrointestinal tract as well as the skin and oral mucosa.

We accumulated the demographic information and analyzed the prevalence of myositis‐specific antibodies (MSAs) in a large cohort across Japan as standard testing for MSAs becomes more widely available. This retrospective, observational, cohort study analyzed the records of individuals aged 0–99 years who are tested for serum MSAs at SRL Incorporation from January 2014 to April 2020 across Japan. An enzyme‐linked immunosorbent assay testing was applied to determine the presence of anti‐aminoacyl tRNA synthetase (anti‐ARS), anti‐Mi‐2, anti‐melanoma differentiation‐associated gene 5 (anti‐MDA5), or anti‐transcriptional intermediary factor 1‐γ (anti‐TIF1γ) (Medical and Biological Laboratories). Anti‐TIF1γ antibody was detected more in male patients than female patients. In contrast, women were predominant in patients with other MSAs. More than half of the anti‐ARS or anti‐TIF1γ antibody‐positive patients were over 60 years old, although anti‐MDA5 or anti‐Mi‐2‐positive patients were mostly under 3‐year evaluation of MSA detection in a routine diagnostic setting. This paper provides clinical images concerning the relationship between four MSA types and the distribution of sex and age in a large population.

Is missing (Short communication)

Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves’ disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves’ disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves’ disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity.