Increased Expression of Integrin α6β4 in the Basement Membrane Zone Lining the Sebaceous Glands in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and sinus tracts. The disease is located primarily in the apocrine gland-bearing skin, including the armpits and groins (1). Previous studies have shown that follicular occlusion is present in the majority of patients at an early stage of the disease (2-5); however, the driving mechanism behind this follicular occlusion is unknown. Recently, diminished periodic acid-Schiff (PAS) staining was found in the basement membrane zone (BMZ) of the sebofollicular junction (SFJ) at the folliculopilosebaceous units (FPSU) in perilesional HS skin (6). The authors suggest that the PAS-negative gaps represent primary defects in the BMZ, leading to fragility of the hair follicle. Diminished expression in one of the glycoproteins in the BMZ of the SFJ might explain these PAS-negative gaps; however, there was no staining for specific glycoproteins in this study. Therefore, we investigated the expression of the most important BMZ components, including type XVII collagen, type VII collagen, laminin-332, and integrin α6β4, of the follicular epidermis relative to the interfollicular epidermis in HS and compared the expression ratio with that of healthy controls. MATERIALS AND METHODSSkin samples were obtained from perilesional skin of patients with HS who underwent surgery (n = 17). Biopsies 4-mm thick were obtained from axillary skin of 8 healthy volunteers. The study was ethically approved by the local review board. PAS, and immunofluorescence (IF) staining for type XVII collagen, type VII collagen, laminin 332, integrin α6 and β4 were performed on all skin samples (for complete details see Appendix S1 1 ). Staining intensities were measured at 5 segments of the FPSU: (i) the interfollicular epidermis (IFE); (ii) the superior segment of the hair follicle; (iii) the inferior segment of the hair follicle; (iv) the sebofollicular junction (SFJ); and (v) the sebaceous gland. The superior segment was defined as the part of the hair follicle extending from the IFE to the SFJ, the inferior segment as the part extending from the SFJ to the bulb. The SFJ was defined as the transition zone from the hair follicle to the sebaceous gland.The intensity of the stainings at the aforementioned individual segments were analysed using Image J software. The ratio of individual segments to the IFE was calculated for both the PAS and IF stainings, with the IFE serving as an internal control for each skin sample. A Mann-Whitney U test was used to compare the differences in these ratios between patients and controls. RESULTSSkin biopsies of 10 patients and 2 controls were excluded due to the lack of an associated sebaceous gland. In total, biopsies of 7 HS patients and 6 controls were studied.The IFE showed a continuous and regular PAS staining pattern in all biopsies with a mean intensity of 143.8 pixels (standard deviation [SD] 11.6) in controls Fig. 1. Periodic acid-Schiff (PAS) and immunofluorescence (IF) staining of the interfollicular epidermis ...

Hidradenitis suppurativa: an update on connecting the tracts

“…However, this study observed significant upregulation of integrins α6 and β4 (signaling molecules with adhesive properties) within the sebaceous gland of HS patients compared to controls. The role of these integrins in HS is unclear at this time 57 .…”

Normal Skin Microbiota is Altered in Pre-clinical Hidradenitis Suppurativa

“…Although the patho genesis of HS is unknown, the role of the cutaneous commensal bacterial community (microbiota) and its potential relationship to the innate immune system in HS appears to be of increasing interest (6)(7)(8)(9). Several studies have hypothesized that a synergistic interaction between the commensal microbiota and aberrant innate immune responses could be a pivotal factor in the pathogenesis of HS (10)(11)(12). However, the structure of the bacterial population, as well as the diversity at strain level, is poorly investigated in patients with HS (13)(14)(15)(16)(17).…”

An Integrating Perspective

“…The increased expression of integrins can be speculated to be either a cause or a consequence of dysbiosis. The findings of Blok et al (1) in the sebaceous glands may therefore indicate an exciting new pathway to pursue in the quest for better understand the complex interplay between bacterial colonization, immunity and structural predisposition of disease.…”

“…They also play a role in cell growth, proliferation, and may participate in the inflammatory response. In this issue, Blok et al (1), describe the increased expression of integrin α6β4 at the basement membrane zone lining the sebaceous glands in hidradenitis suppurativa (HS), a disease in which much remains to be discovered.…”