Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders

Abstract

Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of this study was to investigate the putative role of Erdr1 in alopecias. Skin samples from 21 patients with hair loss disorders and five control subjects were retrieved, in order to assess their expression levels of Erdr1. Results revealed that expression of Erdr1 was significantly downregulated in the epidermis and hair follicles of patients with hair loss disorders, when compared to that in the control group. In particular, the expression of Erdr1 was significantly decreased in patients with alopecia areata. We propose that Erdr1 downregulation might be involved in the pathogenesis of hair loss, and could be considered as a novel biomarker for hair loss disorders.

Keywords: alopecia; erythroid differentiation regulator 1; hair loss; inflammation.

Figure 1

(a) Erythroid differentiation regulator 1 (Erdr1) expression in scalp epidermis of a healthy control; Immunostaining of Erdr1 is shown in brownish-red color; (b) HistoQuant™ measurement for the intensity of Erdr1 expression in scalp epidermis of the healthy control; Red—strong positive; orange—moderately positive; yellow—weakly positive; blue—negative nuclei; white—negative pixels in normal epidermis; (c) Erdr1 expression in the hair follicle of a healthy control; (d) HistoQuant™ measurement for the intensity of Erdr1 expression in hair follicle of the healthy control; (e) The intensities of Erdr1 expression in the epidermis and hair follicles of the healthy control were quantitatively evaluated with an H score using HistoQuant™; Erdr1 immunostaining, original magnification (a–d) ×200; * indicates a p-value less than 0.05.

Figure 2

Erdr1 expression in a healthy scalp hair follicle; (a) Erdr1 expression in the anagen phase of the follicle; A high-power image of Erdr1-positive cells in the outer root sheath of the follicle is shown; (b) Healthy hair follicle in the catagen phase; A high-power image of Erdr1-positive cells in the outer root sheath of the catagen hair follicle is shown; (c) Erdr1 expression in the telogen phase; Erdr1 immunostaining, original magnification (a–c) ×50; inserts ×200.

Figure 3

(a–d) Clinical photograph of a healthy control, alopecia areata, alopecia areata with good clinical response, and alopecia areata with poor clinical response; (e–h) Erdr1 staining patterns of epidermis in a healthy control, alopecia areata, alopecia areata with good clinical response, and alopecia areata with poor clinical response. (i–l) HistoQuant™ measurement for the intensity of Erdr1 expression in the epidermis of a healthy control, alopecia areata, alopecia areata with good clinical response, and alopecia areata with poor clinical response; Red—strong positive; orange—moderately positive; yellow—weakly positive; blue—negative nuclei; white—negative pixels; (m–p) Erdr1 staining patterns of the hair follicle in a healthy control, alopecia areata, alopecia areata with good clinical response, and alopecia areata with poor clinical response; (q–t) HistoQuant™ measurement for the intensity of Erdr1 expression in the hair follicle of a healthy control, alopecia areata, alopecia areata with good clinical response, and alopecia areata with poor clinical response; (u) The intensity of Erdr1 expression in the epidermis in alopecia areata was quantitatively evaluated using the HistoQuant™ H score; (v) Erdr1 expression in the hair follicles of alopecia areata was quantitatively compared to each group using the H score; Erdr1 immunostaining, original magnification (e–i) ×200; (m–t) ×400. AA: alopecia areata. * indicates a p-value less than 0.05.

Figure 4

Erdr1 expression in scarring alopecia. The intensity of Erdr1 expression in scarring alopecia was quantitatively evaluated using the HistoQuant™ H score; (a) The mean H score for Erdr1 expression in the epidermis; (b) Erdr1 expression levels in hair follicles of patients with scarring alopecia. * indicates a p-value less than 0.05.

Figure 5

(a) Representative clinical photograph of neutrophilic scarring alopecia showing folliculitis decalvans; (b) Erdr1 staining patterns of the epidermis in neutrophilic scarring alopecia; (c) HistoQuant™ measurement for the intensity of Erdr1 expression; Red—strong positive; orange—moderately positive; yellow—weakly positive; blue—negative nuclei; white—negative pixels; (d) Erdr1 staining patterns of the hair follicle in neutrophilic scarring alopecia; (e) HistoQuant™ measurement for the intensity of Erdr1 expression in the hair follicle of neutrophilic scarring alopecia; (f) Representative clinical photograph of lymphocytic scarring alopecia showing frontal fibrosing alopecia; (g) Erdr1 staining patterns of the epidermis in lymphocytic scarring alopecia; (h) HistoQuant™ measured the intensity of epidermal Erdr1 expression in lymphocytic scarring alopecia; (i) Erdr1 staining patterns of the hair follicle; (j) HistoQuant™ measured the intensity of Erdr1 expression in the hair follicle; Erdr1 immunostaining, original magnification (b–e,g,h) ×200; (i,j) ×400.

Figure 6

(a) Clinical photograph of traction alopecia; (b) Erdr1 staining patterns of the epidermis in traction alopecia; (c) HistoQuant™ measurement for the intensity of epidermal Erdr1 expression in traction alopecia patients; (d) Erdr1 staining patterns of the hair follicle in traction alopecia; (e) HistoQuant™ measured the intensity of Erdr1 expression in the hair follicles; (f) Clinical photograph of a healthy control; (g) Erdr1 staining patterns of the epidermis in healthy control; (h) HistoQuant™ measurement for the intensity of epidermal Erdr1 expression in the healthy control; (i) Erdr1 staining patterns of the hair follicle from the healthy control; (j) HistoQuant™ measurement for the intensity of Erdr1 expression in hair follicles; (k) The intensity of Erdr1 expression in traction alopecia was quantitatively determined using the HistoQuant™ H score and compared to that in healthy controls; Erdr1 immunostaining, original magnification (b,c,g,h) ×200; (d,e,i,j) ×400; * indicates a p-value less than 0.05.

Figure 7

Comparison of Erdr1 expression in alopecia subgroups; The intensities of Erdr1 expression levels in alopecia areata, scarring alopecia, and traction alopecia were quantitatively evaluated using the HistoQuant™ H score; (a) The mean H score for Erdr1 expression in the epidermis of various hair loss disorders; (b) Erdr1 expression in the hair follicles of various hair loss disorders. * indicates a p-value less than 0.05.