Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood

Kalish, Richard S.; Johnson, Karyn L.; Hordinsky, Maria

doi:10.1001/archderm.128.8.1072

Cited by 24 publications

(18 citation statements)

References 38 publications

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“…Evidence is accumulating in recent years to demonstrate that alopecia areata (AA) is an autoreactive skin disease mediated by activated/autoreactive T lymphocytes. In fact, earliest histologic signs of AA are peri‐ and intrafollicular inflammatory infiltrates consisting of activated T lymphocytes (76,77), especially of CD4 + type (78), and autoreactive T lymphocytes have been found not only in scalp biopsy specimens but also in peripheral blood (79). Such autoreactive/activated T cells are indeed responsible for AA, because T cells isolated from scalp of patients with AA and cultured with hair follicle homogenates were able to induce both hair loss and the clinical findings of AA when injected into autologous scalp grafted onto SCID mice (80,81); further, the cytotoxic modalities such autoreactive T cells use to kill hair follicle keratinocytes were recently elucidated (78).…”

Section: Autoreactive Skin Diseases Can Be Associated With Autoreactimentioning

confidence: 99%

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Panfilis¹

2002

Experimental Dermatology

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'Activation-induced cell death': a special program able to preserve the homeostasis of the skin?De Panfilis G. 'Activation-induced cell death': a special program able to Abstract: The 'activation-induced cell death' (AICD) is a molecular system leading to death of antigen-activated T lymphocytes, in order to avoid accumulation of harmful cytokine-releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95-/CD95-L-mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95-/CD95-L-mediated AICD of such strong pro-inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases. Giuseppe De Panfilis Accepted for publication 18 June 2001 IntroductionEvidence is accumulating that cell death by apoptosis plays an important role in cutaneous biology and disease (reviewed in 1-5). Nevertheless, although in the past few years a large body of studies concerning the death receptors and molecular mechanisms involved in apoptosis have been carried out, our understanding of how these molecules act remains largely limited and is therefore difficult to translate the knowledge gained from these studies into clinical settings, including skin homeostasis and disease (1).However, at least one special apoptotic machine can be assessed, in our opinion, as playing a pivotal role to preserve the homeostasis of the skin, namely, the program termed 'activation-induced 1 cell death' (AICD). AICD, in fact, is an important mechanism for the regulation and limitation of cellular immune responses, in that antigen-reactivated T cells die, to prevent accumulation of excessive numbers of harmful cytokine-releasing T lymphocytes (reviewed in 6). The skin is indeed continuously challenged by a variety of antigenic stimuli, and a program should exist to prevent the perpetuous accumulation in the skin of expanded populations of antigen-reactive, activated T cells. Otherwise, activated/autoreactive T cells which are not removed after specific activation can persist within the skin, and may sustain inflammatory/autoreactive conditions. The aim of this review, therefore, was to explore the possible role played by AICD in preserving the homeostasis of the skin. If this was the case, in fact, molecular mechanisms work- De Panfilising in AICD should be defective in inflammatory/ autoreacti...

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Section: Autoreactive Skin Diseases Can Be Associated With Autoreactimentioning

confidence: 99%

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Panfilis¹

2002

Experimental Dermatology

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“…Alopecia areata is an asymptomatic, non scarring hair loss characterized by remis sions and exacerbations [9][10][11][12]. In HIVseronegative individuals, this condition has occurred prior to, concurrent with, or follow ing the development of other diseases such as Addison's disease, chronic mucocutaneous candidiasis, diabetes mellitus, Down's syn drome, Hashimoto's thyroiditis, idiopathic hypoparathyroidism, pernicious anemia, pre mature ovarian failure, ulcerative colitis, or vitiligo [12].…”

Section: Introductionmentioning

confidence: 99%

Acquired Eyelash Trichomegaly and Alopecia areata in a Human Immunodeficiency Virus-Infected Patient

1996

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We describe a human immunodeficiency virus (HIV) seropositive man with acquired eyelash trichomegaly and alopecia areata. This combination of clinical manifestations is intriguing since the new onset of elongated eyelashes in patients with acquired immunodeficiency syndrome has usually been associated with severe immunosuppression and alopecia areata has a presumed autoimmune etiology that requires T cell activation. The occurrence of these dichotomous conditions illustrates the potential selective pathogenesis of progressive HIV infection.

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“…Alopecia areata is characterized by patchy hair loss with perifollicular and intrafollicular T-cell infiltration (Kalish et al , 1992;McDonagh & Messenger, 1996). The association of alopecia areata with autoimmune diseases including thyroid disorders, pernicious anaemia and vitiligo is well established (Muller & Winkelmann, 1963;Cunliffe et al , 1968) and alopecia areata itself is conventionally regarded as an autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of the interleukin‐1 receptor antagonist and its homologue IL‐1L1 in alopecia areata: strong severity association and possible gene interaction‡

Tazi-Ahnini

Cox²,

McDonagh

et al. 2002

European Journal of Immunogenetics

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Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.

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Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood

Cited by 24 publications

References 38 publications

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

‘Activation‐induced cell death’: a special program able to preserve the homeostasis of the skin?

Acquired Eyelash Trichomegaly and Alopecia areata in a Human Immunodeficiency Virus-Infected Patient

Genetic analysis of the interleukin‐1 receptor antagonist and its homologue IL‐1L1 in alopecia areata: strong severity association and possible gene interaction‡

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