Clinically Applicable Deep Learning Framework for Measurement of the Extent of Hair Loss in Patients With Alopecia Areata.
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ABSTRACT:
SUBMITTER: Lee S
PROVIDER: S-EPMC7489853 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Clinically Applicable Deep Learning Framework for Measurement of the Extent of Hair Loss in Patients With Alopecia Areata.
Lee Solam S Lee Jong Won JW Choe Sung Jay SJ Yang Sejung S Koh Sang Baek SB Ahn Yeon Soon YS Lee Won-Soo WS
JAMA dermatology 20200901 9
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Project description:BackgroundAlopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases.MethodsHair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model.ResultsAA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo.ConclusionsThis study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.
| S-EPMC8532319 | biostudies-literature
Project description:Alopecia areata (AA) involves an aberrant immune attack on the hair follicle (HF), which leads to hair loss. Previous genetic data from our lab pointed to a connection between macroautophagy/autophagy and AA pathogenesis, and GWAS identified STX17, CLEC16A and BCL2L11/BIM as risk factors for AA. Additionally, AA patients have copy number deletions in region spanning the ATG4B gene. To test whether autophagy might contribute to disease pathogenesis in AA, we investigated autophagic activity in C3H/HeJ mouse model. We found that autophagy protein SQSTM1 accumulated in HF of AA mice, while in immune cells from AA skin-draining lymph nodes SQSTM1 was not altered, suggesting that autophagic activity is inhibited in the HF of AA mice. Induction of autophagy with Tat-BECN1 peptide attenuated AA, while treatment with the autophagy blocker chloroquine promoted disease, compared to untreated AA mice. Together, our findings suggest the involvement of impaired autophagy in disease pathogenesis of AA.Abbreviations: AA: alopecia areata; CQ: chloroquine; GWAS: genome-wide association studies; HF: hair follicle; MHC: major histocompatibility complex; SDLN: skin-draining lymph nodes.
| S-EPMC9809940 | biostudies-literature
Project description: Not available
| S-EPMC10855715 | biostudies-literature
Project description:Alopecia areata (AA) is a chronic autoimmune hair loss disease that affects several million men, women and children worldwide. Previous studies have suggested a link between autoimmunity, stress hormones, and increased cardiovascular disease risk. In the current study, histology, immunohistology, quantitative PCR (qPCR) and ELISAs were used to assess heart health in the C3H/HeJ mouse model for AA and heart tissue response to adrenocorticotropic hormone (ACTH) exposure. Mice with AA exhibited both atrial and ventricular hypertrophy, and increased collagen deposition compared to normal-haired littermates. QPCR revealed significant increases in Il18 (4.6-fold), IL18 receptor-1 (Il18r1; 2.8-fold) and IL18 binding protein (Il18bp; 5.2-fold) in AA hearts. Time course studies revealed a trend towards decreased Il18 in acute AA compared to controls while Il18r1, Il18bp and Casp1 showed similar trends to those of chronic AA affected mice. Immunohistochemistry showed localization of IL18 in chronic AA mouse atria. ELISA indicated cardiac troponin-I (cTnI) was elevated in the serum and significantly increased in AA heart tissue. Cultures of heart atria revealed differential gene expression between AA and control mice in response to ACTH. ACTH treatment induced significant increase in cTnI release into the culture medium in a dose-dependent manner for both AA and control mice. In conclusion, murine AA is associated with structural, biochemical, and gene expression changes consistent with cardiac hypertrophy in response to ACTH exposure.
| S-EPMC3637254 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions.MethodsWe engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele.FindingsWe identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs).InterpretationOur results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events.FundingThis work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).
| S-EPMC7317227 | biostudies-literature
Project description:ImportanceAlopecia areata (AA) is a complex immune-mediated disorder that causes nonscarring hair loss. Previous reports have documented preferential targeting of pigmented hair follicles with sparing of gray, nonpigmented hair follicles in alopecia lesions. Thus, immune targeting of melanogenesis-associated proteins in melanocytes and keratinocytes represents a potential mechanism for the inflammation that targets anagen hairs in alopecia areata.ObjectiveTo investigate the association of alopecia areata with hair color among White residents of the UK.Design, setting, and participantsThis matched, case-control study conducted in October 2020 used a large prospectively acquired cohort and included data that were collected from the UK Biobank, a large-scale prospective resource designed to study phenotypic and genotypic determinants in adults. A total of 502 510 UK Biobank participants were reviewed for inclusion. Among these individuals, 1673 cases of alopecia areata with reported hair color were captured and matched by age and sex to 6692 controls without alopecia areata using 1:4 matching.Main outcomes and measuresConditional logistic regression analysis was performed, in which the outcome variable was alopecia areata and the main predictor was natural hair color before graying. The variables considered included diabetes, hypothyroidism, hyperthyroidism, and vitiligo.ResultsOf 464 353 participants, 254 505 (54.8%) were women, and the mean (SD) age for those with alopecia areata was 46.9 (16.5) years. Alopecia areata was significantly more common in individuals with black (adjusted odds ratio [aOR], 2.97; 95% CI, 2.38-3.71) and dark brown hair (aOR, 1.26; 95% CI, 1.11-1.42) compared with light brown hair. In contrast, blond individuals exhibited significantly decreased alopecia areata compared with those with light brown hair (aOR, 0.69; 95% CI, 0.56-0.85). Red hair color was not significantly different from light brown hair.Conclusions and relevanceThe findings of this matched case-control study seem to indicate that alopecia areata is modulated by natural hair color, preferentially targeting darker hair. Our results support a previously proposed model of alopecia areata in which immunity is directed against melanogenesis-associated proteins in the anagen hair follicles. However, further study is needed to more precisely understand the immunopathogenic association between alopecia areata and hair color.
| S-EPMC7948107 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) is one of the most common autoimmune diseases and targets the hair follicles, with high impact on the quality of life and self-esteem of patients due to hair loss. Clinical management and outcomes are challenged by current limited immunosuppressive and immunomodulating regimens.MethodsWe have developed a Stem Cell Educator therapy in which a patient's blood is circulated through a closed-loop system that separates mononuclear cells from the whole blood, allows the cells to briefly interact with adherent human cord blood-derived multipotent stem cells (CB-SC), and returns the "educated" autologous cells to the patient's circulation. In an open-label, phase 1/phase 2 study, patients (N = 9) with severe AA received one treatment with the Stem Cell Educator therapy. The median age was 20 years (median alopecic duration, 5 years).ResultsClinical data demonstrated that patients with severe AA achieved improved hair regrowth and quality of life after receiving Stem Cell Educator therapy. Flow cytometry revealed the up-regulation of Th2 cytokines and restoration of balancing Th1/Th2/Th3 cytokine production in the peripheral blood of AA subjects. Immunohistochemistry indicated the formation of a "ring of transforming growth factor beta 1 (TGF-β1)" around the hair follicles, leading to the restoration of immune privilege of hair follicles and the protection of newly generated hair follicles against autoimmune destruction. Mechanistic studies revealed that co-culture with CB-SC may up-regulate the expression of coinhibitory molecules B and T lymphocyte attenuator (BTLA) and programmed death-1 receptor (PD-1) on CD8β(+)NKG2D(+) effector T cells and suppress their proliferation via herpesvirus entry mediator (HVEM) ligands and programmed death-1 ligand (PD-L1) on CB-SCs.ConclusionsCurrent clinical data demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of AA. This innovative approach produced lasting improvement in hair regrowth in subjects with moderate or severe AA.Trial registrationClinicalTrials.gov, NCT01673789, 21 August 2012.
| S-EPMC4417286 | biostudies-literature
Project description: Not available
| S-EPMC6029960 | biostudies-literature
Project description:Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
| S-EPMC5573125 | biostudies-other
Project description:BackgroundValid patient-reported outcome (PRO) measures are required to evaluate alopecia areata (AA) treatments.ObjectivesTo develop a content-valid and clinically meaningful PRO measure to assess AA scalp hair loss with scores comparable with the five-response-level Alopecia Areata Investigator Global Assessment (AA-IGA™).MethodsA draft PRO measure was developed based on input from 10 clinical experts in AA. The PRO measure was cognitively debriefed, modified and finalized through two rounds of qualitative semistructured interviews with patients with AA who had experienced ≥ 50% scalp hair loss. Data were thematically analysed.ResultsAdults (round 1: n = 25; round 2: n = 15) and adolescents aged 15-17 years (round 1: n = 5) in North America participated. All patients named scalp hair loss as a key AA sign or symptom. Patients demonstrated the ability to self-report their current amount of scalp hair using percentages. In round 1 not all patients interpreted the measurement concept consistently; therefore, the PRO was modified to clarify the measurement concept to improve usability. Following modifications, patients in round 2 responded without difficulty to the PRO measure. Patients confirmed that they could use the five-level response scale to rate their scalp hair loss: no missing hair, 0%; limited, 1-20%; moderate, 21-49%; large, 50-94%; nearly all or all, 95-100%. Almost all patients deemed hair regrowth resulting in ≤ 20% scalp hair loss a treatment success.ConclusionsThe Scalp Hair Assessment PRO™ is a content-valid, clinically meaningful assessment of distinct gradations of scalp hair loss for evaluating AA treatment for patients with ≥ 50% hair loss at baseline.
| S-EPMC7754291 | biostudies-literature