Genetic association of<i>HLA‐DQB1</i>and<i>HLA‐DRB1</i>polymorphisms with alopecia areata in the Italian population

Megiorni, Francesca; Pizzuti, Antonio; Mora, Barbara; Rizzuti, A; Garelli, Valentina; Maxia, Cristina; Carlesimo, Marta; Fotruna, M.C.; Chiaie, R. Delle; Cavaggioni, Gabriele; Rossi, Alfredo

doi:10.1111/j.1365-2133.2011.10466.x

Cited by 34 publications

(22 citation statements)

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“…Hence, these SNPs, being located in the promoter regions of FOXP3 and ICOSLG genes, may have a functional role directly correlated with the level of gene transcription and mRNA expression. Moreover, the presence and frequency of these polymorphisms were correlated with those of the DQB1*03(DQ7) allele, which was recently recognized as a predisposing allele for the disease in the Italian population of AA patients [8]. The results show the strong association between AA and both FOXP3 and ICOSLG gene SNPs, whose presence also correlated with the DQB1*03(DQ7) allele.…”

Section: Introductionmentioning

confidence: 66%

“…Patients were recruited from the Department of Internal Medicine and Medical Specialities, 'Sapienza' University of Rome and from Associazione Nazionale Alopecia Areata. In Megiorni et al [8] study, 96 of these patients had been already genotyped for HLA-DQB1*03(DQ7) polymorphism. The diagnosis of AA was performed according to specific criteria [26].…”

Section: Patients and Controlsmentioning

confidence: 99%

“…Indeed, focal T lymphocytes infiltration [4] and deposition of hair folliclespecific autoantibodies [5] are present in anagen stage (growing) hair follicles. Susceptibility to AA has been referred to a polygenic complex [6,7] comprising immune system genes coding for the human leukocyte antigens (HLA) or other immune-related gene products [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

et al. 2012

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Alopecia areata (AA), an autoimmune disease affecting anagen stage hair follicles, is associated with polymorphisms in immune-related genes and with decreased number of CD4? CD25? T regulatory cells (Treg). Treg function is modulated by the forkhead box protein 3 (FOXP3) transcription factor and by inducible costimulator (ICOS), through interaction with the relative ligand, ICOSLG, whose genes are polymorphic. The aim of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) of the rs2294020 FOXP3 and/ or rs378299 ICOSLG genes may be associated with AA. A case-control study was performed in 120 AA patients and 84 controls. SNPs were analyzed by gene sequencing. FOXP3 and ICOSLG gene expressions were analyzed by real-time PCR. Increased frequencies of the genotype carrying the FOXP3 rs2294020-3675(A) [P = 0.002, OR (95 % CI): 2.55 (1.2-2.7)] or the ICOSLG rs378299-509(C) [P = 0.01, OR (95 % CI): 2.21 (1.1-2.6)] allelic variants were observed in AA patients than in controls. The genotype carrying the combination of the FOXP3 rs2294020-3675(A) and ICOSLG rs378299-509(C) allelic variants with the HLA DQB1*03 allele was more frequently present in AA patients than in controls (P = 0.04). The presence of the FOXP3 rs2294020-3675(A) or the I-COSLG rs378299-509(C) allelic variant was associated with reduced relative gene expression in AA patients. These data suggest that rs2294020 SNP of FOXP3 gene and rs378299 SNP of ICOSLG gene are associated with AA and with a reduced expression of the FOXP3 and ICOSLG genes in alopecia patients.

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Section: Introductionmentioning

confidence: 66%

Section: Patients and Controlsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

et al. 2012

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“…Classical upregulators of MHC I expression like interferon (IFN)-γ [31], tumor necrosis factor (TNF)-α, and interleukin (IL)-1β [63] are enhanced in AA lesions and down-modulators of MHC I expression (IL-10, αMSH, IGF-1, TGFβ) are modified in AA lesions as well [18,31,64]. Specific genetic polymorphisms of HLA-DQB1 and HLA-DRB1, which belong to the HLA class II beta chain paralogs, strongly correlate to increased probability of AA onset [65][66][67].…”

Section: Immune Privilege Collapse In Alopecia Areatamentioning

confidence: 99%

The role of lymphocytes in the development and treatment of alopecia areata

Guo

Cheng

Shapiro

et al. 2015

Expert Review of Clinical Immunology

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SummaryAlopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri-and intra-follicular regions, and hair follicle disruption. Both CD4+ and CD8+ lymphocytes are abundant in AA lesions; however, CD8+ cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8+ cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the selfantigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8+ cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches.

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“…They revealed low levels of vitamin D3 (13,5 ng/ml) and high levels of red cells (6. (1). The patient started systemic therapy using triamcinalone acetonide (40 mg/ml twice a month for three months) and topical therapy with clobetasol propionate.…”

confidence: 99%

Alopecia areata and hypertrichosis: a case report

Rossi¹

2012

P. & R.

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SummaryHypertrichosis is an abnormal hair growth for age, sex, race or for a particular body area of an individual. For this special clinical condition a differential diagnosis is proposed with hirsutism: male-pattern hair growth in a female or child. It tipically involves the upper lip, chin, cheeks, breast areola, linea alba and the top of the pubic triangle and it is, usually, due to an androgen excess. The most common cause in female is the polycystic ovary syndrome but other causes, in both sexes, include hyperandrogenic insulin resistance acanthosis nigricans syndrome, androgen-secreting tumors, and androgen drug intake. When in women it is accompanied to other masculinization signs it is usually definied virilization. This clinical condition is associated with a more complete voice change, changes in libido, and clitoromegaly. Two different mechanisms are proposed to explain hypertrichosis's development: conversion of vellus to terminal hairs and changes in the hair-growth cycle. Hair cycle is characterized by the switch from a period of very rapid growth, pigmentation, and hair-shaft production (anagen, the active-growth phase, with classification ranging from stages I to VI) to a short, apoptosis-driven phase of organ involution (catagen). After catagen, the hair follicle enters a period of relative quiescence (telogen) before it reenters anagen. This regenerative cycle is made possible by an abundance of keratinocyte and melanocyte stem cells located for the most part in the so-called bulge area. Alopecia areata is a multifactorial autoimmune disease, which involves several genes, characterized by well-circumscribed patches of hair loss especially from the scalp and typically it presents as one or more well demarcated isolated, round smooth areas of complete hair loss patches of no scarring alopecia on skin of overtly normal appearance without clinical signs of skin inflammation, in which the scalp feels slightly depressed because of loss of the supportive effect of the hair shafts. The pattern of scalp involvement may be patchy, mosaic, confluent or diffuse. Different forms of AA may evolve into one another during a single episode or with recurrent episodes. The pathobiology of this chronic, relapsing hair-loss disorder is not fully understood but studies show that hair follicle melanocyte-and/or anagen-associated autoantigens play a key role in AA pathogenesis which is based, also, on immune privilege collapse; thus the available therapies are disappointing. In contrast to scarring hair loss induced by other chronic, inflammatory skin diseases, lesional hair follicles in AA, generally, do not scar and can regrow. Mild disease has a high rate of spontaneous remission, and even cases of severe AA universalis can spontaneously experience complete hair regrowth. The impact of this skin disease on the lives of patient tends to be underestimated or even dismissed as simply a "cosmetic problem". Alopecia areata exemplifies such a condition, owing to its substantial disease burden and its often devastating e...

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Genetic association ofHLA‐DQB1andHLA‐DRB1polymorphisms with alopecia areata in the Italian population

Abstract: Our data show a correlation between the HLA-DQB1 locus and the occurrence of AA in Italy supporting DQB1*03(DQ7) as a predisposing allele for the disease and the relevance of the HLA genetic test in the clinical management of AA.

Cited by 34 publications

References 25 publications

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

Single nucleotide polymorphisms in the promoter regions of Foxp3 and ICOSLG genes are associated with Alopecia Areata

The role of lymphocytes in the development and treatment of alopecia areata

Alopecia areata and hypertrichosis: a case report

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