To report on the biometric findings of adults and children with Marfan syndrome (MFS) recruited from 2 annual National Marfan Foundation conferences (2012 and 2015).
Subjects diagnosed with MFS by Ghent 2 nosology were included for analysis. Subjects were divided into “adults” (≥16 years of age) and “children” (5–15 years of age). Biometric data included values for refractive error, axial length (AL), corneal curvature, anterior chamber depth, lens thickness, and central corneal thickness.
Of the 117 subjects evaluated, 74 (35 adults, 32 children, and 7 children <5 years of age) had a definite diagnosis of MFS and were included in the study. The AL was longer (25.25 ± 0.32 mm vs 24.24 ± 0.33 mm, P [ .03) and the lens was thicker (3.94 ± 0.09 mm vs 3.62 ± 0.10 mm, P [ .03) in adults. Both groups had flat corneas (average keratometry [Kmed] of 41.59 ± 0.35 diopters [D] in adults vs 40.89 ± 0.36 D in children, P [ .17). A negative correlation was found between AL and Kmed (L0.33, P < .001). The corneas of patients with MFS with ectopia lentis (EL) were significantly flatter and with higher degree of corneal astigmatism compared to patients without EL (Kmed of 40.68 ± 0.31 D vs 41.75 ± 0.28 D, P < .01 and corneal astigmatism of 1.68 ± 0.16 D vs 1.13 ± 0.14 D, P =.01).
Children with established MFS have flat corneas at least to the same degree as adults. Corneas of patients with MFS with EL are flatter and have a higher degree of corneal astigmatism. We strongly suggest that corneal parameters should be measured if MFS is suspected, especially in children that may not yet have developed EL.
In the GWAS group, age at onset was 36 years and in the non-GWAS group 28 years. The difference is mainly owing to the inclusion of a subset of individuals from a paediatric cohort (disease onset before 15 years of age) into the non-GWAS samples whereas the GWAS samples included only individuals with adult onset of disease.Strong association to HLA genes is a hallmark of common immune-mediated diseases. HLA genes are extremely polymorphic with minor sequence variation between genotypes. In view of increasing demand for dissection of genetic and clinical heterogeneity of many common immunologically based diseases, precise determination of HLA genotypes will become critical. In this respect, we propose that the method presented herein represents a real contribution in the psoriasis field.
AcknowledgementsThe authors thank Anna-Lena Kastman, Anna Ehrensvärd, Kerstin Bergh, Leonid Padyukov and Maria Seddighzadeh for the excellent assistance, technical support and advice. This work was supported by grants from the Swedish Medical Research Council, the Swedish Psoriasis Association, the Welander and Finsen Foundations, Stockholm County and Karolinska Institutet.
Conflict of interestsThe authors have declared no conflicting interests.
Supporting InformationAdditional Supporting Information may be found in the online version of this article: Table S1. HLA-Cw*06:02 readings from four SNPs genotypes.Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Abstract: Interferon-c (IFNc)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and ⁄ or restore IFNc-induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor-like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFNc, with CGRP added before or after. Adding CGRP after IFNc administration ('restoration assay') failed to downregulate IFNc-induced ectopic MHC class I expression, while MHC class II expression was reduced. However, administering CGRP before IFNc application ('protection assay') significantly reduced the IFNc-induced overexpression and ectopic expression of MHC class I and II and reduced the increased degranulation of perifollicular mast cells induced by IFNc. This suggests that CGRP may not restore HF-IP once it has collapsed, but may protect it from collapsing. Therefore, CRLR stimulation might help to retard AA progression.
Immune privilege (IP) is important in maintaining ocular health. Understanding the mechanism underlying this dynamic state would assist in treating inflammatory eye diseases. Despite substantial progress in defining eye IP mechanisms, because of the scarcity of human ocular tissue for research purposes, most of what we know about ocular IP is based on rodent models (of unclear relevance to human eye immunology) and on cultured human eye-derived cells that cannot faithfully mirror the complex cell-tissue interactions that underlie normal human ocular IP in situ. Therefore, accessible, instructive, and clinically relevant human in vitro models are needed for exploring the general principles of why and how IP collapses under clinically relevant experimental conditions and how it can be protected or even restored therapeutically. Among the few human IP sites, the easily accessible and abundantly available hair follicle (HF) may offer one such surrogate model. There are excellent human HF organ culture systems for the study of HF IP in situ that instructively complement in vivo autoimmunity research in the human system. In this article, we delineate that the human eye and HF, despite their obvious differences, share key molecular and cellular mechanisms for maintaining IP. We argue that, therefore, human scalp HFs can provide an unconventional, but highly instructive, accessible, easily manipulated, and clinically relevant preclinical model for selected aspects of ocular IP. This essay is an attempt to encourage professional eye researchers to turn their attention, with appropriate caveats, to this candidate surrogate model for ocular IP in the human system.
Cutaneous juvenile xanthogranulomas are generally limited to the skin. Because eye involvement is rare, a routine eye examination is of low yield and probably not warranted in children with no ocular or visual symptoms. New recommendations for systemic screening could not be drawn from this study.
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