Expression of Follicular Sheath Keratins in the Normal Nail With Special Reference to the Morphological Analysis of the Distal Nail Unit

Abstract

Background: The origin and the histology of the distal nail unit remain controversial. For some authors the nail bed is completely derived from the matrix epithelium and is not a self-regenerating, independent structure. The term onycholemmal keratinization has been used variably to describe both the so-called superficial horny layer without the granular layer of the nail bed, and the epidermal keratin of the hyponychium (HYN) and the eponychium. On the other hand, several contradictory systems of comparisons and homologies between components of the nail unit and those of the follicular sheaths have been proposed. Recently, the expression profiles of the epithelial keratins of the follicular sheaths have been determined in the human anagen hair follicle, but they have been only partially analyzed in the nail unit. Objective: This study was conducted to elucidate the morphology of the distal nail unit. To clarify the degree of homology between the nail unit and follicular sheaths, a selected set of keratins (K) was used. Methods: Formalin-fixed paraffin sections of adult nails were examined using mono- and polyclonal keratin antibodies, which are characteristic, respectively, for the inner root sheath, the companion layer, and the outer root sheath, as well as K10 and the antibody Ki-67 (antigen expressed in cycling cells). Longitudinal as well as transverse sections were investigated. Results: The pattern of the keratins in the nail unit differs from that of the follicle in two points: the lack of an IRS-like compartment and of the companion layer. The expression of K6hf was observed almost exclusively in the nail bed. K6 and K16 were expressed in the eponychium, the apical matrix, and the nail bed, but not in the ventral matrix. Distribution of K6 and K16 was essentially suprabasal. On the basis of morphologic and biochemical considerations, the distal nail unit can be divided into three segments. The nail bed, which represents the main segment of distal nail unit, does not differentiate into a thin, orthokeratinizing surface. The nail isthmus is typified by a peculiar mode of keratinization (ie, a compartment of pale, nucleated corneocytes), which is closely adherent to the inferior border of the nail plate, including its distal free edge. The nail isthmus presents a profile of keratin expression in transition between the nail bed and HYN. The keratin pattern of the nail bed, including K6hf, is maintained. However, the nail isthmus differs from the nail bed in that K10 is only present in nail isthmus. The HYN differs from the nail isthmus in that K6hf is absent in HYN. In addition, the HYN shows, progressively or abruptly, a loss of expression of K6/16, and K5/17 expression returns to a basal pattern. The mean Ki-67 labeling index of ventral matrix, nail bed including nail isthmus, and distal HYN were, respectively, 21.16%, 5.2%, and 16.43%. Conclusion: The nail bed epithelium is an independent, specialized, epithelial structure with a true basal layer presenting a heterogeneous but significant proliferative activity. The so-called horny layer of the nail bed corresponds, in fact, to the superficial cells of the spinous layer of the nail bed. In this zone, the intercellular “spines” are barely detectable between cells replete with pink to brightly eosinophilic cytoplasm. The interlocking of the inferior border of the nail plate and the surface of the bed explain the strong attachment between the two tissues. The nail isthmus represents a transitional zone between the nail bed and the HYN and exhibits a pattern of keratinization different from the HYN. The cornified layer of the nail isthmus closely adheres to the undulating inferior surface of the nail plate; the two grow forward together. Therefore, the horny layer of the nail isthmus offers an effective sealing of the distal nail bed, preventing onycholysis. The terms matricial keratinization and onycholemmal keratinization could describe, respectively, the keratinization of the matrix and the nail isthmus.