Clinically Applicable Deep Learning Framework for Measurement of the Extent of Hair Loss in Patients With Alopecia Areata.
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SUBMITTER: Lee S
PROVIDER: S-EPMC7489853 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: Not available
| S-EPMC6029960 | 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: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
Project description:BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-? transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3-6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment. RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers. CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA. TRIAL REGISTRATION. Clinicaltrials.gov NCT01950780. FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).
| S-EPMC5033756 | biostudies-literature
Project description: Not available
| S-EPMC3230136 | biostudies-literature
Project description:BackgroundAlopecia areata (AA) is a T-cell-mediated autoimmune disease and affects up to 2% of the population. There is a need for a more profound and rigorous understanding of the structure and composition of human hair affected by AA in order to manage this disease. The aim of this article is to understand the effects of AA on the structure and composition of human hair.MethodsSeveral physico-chemical investigation methods, such as Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy-Dispersive X-ray Spectroscopy (EDX), and microbeam Small Angle X-ray Scattering (SAXS), were used to analyze human hair samples obtained from healthy donors and patients with AA.ResultsSEM revealed more severe hair surface defects for the white regrown hair (W-AA) samples. TEM showed the presence of air-like vesicles located in the endocuticle of regrown hair. Analysis of ultrathin sections of W-AA showed the existence of empty vesicles and smaller melanin granules compared to control samples. SAXS demonstrated that unaffected hair of patients with AA (B-AA) and W-AA melanin aggregates are different in their sizes and shapes compared to the control samples. EDX data showed that W-AA elemental composition was significantly different from the other sample groups. Our study showcases promising non-invasive techniques for a better and more accurate understanding of changes in the internal structure and composition of hair affected by AA.
| S-EPMC6968496 | biostudies-literature
Project description:Alopecia areata (AA) is a common disease characterized by nonscarring hair loss. There are no satisfactory therapies for extensive cases. Systemic immune suppressants are usually used despite their nonspecific actions and often associated side effects. Apremilast is an oral, small-molecule, inhibitor of phosphodiesterase 4 approved for the treatment of psoriasis and psoriatic arthritis. Its use in AA has shown variable results. Whereas a recent reduced clinical trial concluded a lack of efficacity, several case reports demonstrate a significant improvement. We report four cases of extensive AA successfully treated with apremilast.
| S-EPMC6830030 | biostudies-literature