Harish P. Patel

Linear immunofluorescence staining of the cutaneous basement membrane zone produced by pemphigoid antibodies: the result of hemidesmosome staining.

Bullous pemphigoid autoantibodies bind the basement membrane zone of stratified squamous epithelium in a linear pattern, as shown by indirect immunofluorescence; however, other patterns of staining, such as tubular (with convolutions), cytoplasmic, and membranous, have been noted. Recently, by using indirect immunoelectron microscopy, we have shown that bullous pemphigoid antibodies bind specifically to hemidesmosomes. The purpose of this investigation was to correlate the various patterns of basement membrane zone staining by bullous pemphigoid antibodies by immunofluorescence and to correlate these patterns with the ultrastructural findings. We employed adult human skin, neonatal human foreskin, neonatal mouse skin, and rabbit cornea as substrates for electron microscopy and indirect immunofluorescence using bullous pemphigoid serum. For indirect immunofluorescence, cryosections were obtained at vertical, oblique, and horizontal planes with respect to the basement membrane zone. We show that the immunofluorescence band of basement membrane zone staining results from the coalescence of fluorescence from individual hemidesmosomes. We also show that the pattern of basement membrane zone staining depends on the ultrastructural morphology of the basement membrane zone in each tissue and on the angle of sectioning.

Pili torti in association with citrullinemia

A 2 1/2-year-old white girl with citrullinemia accompanied by neurologic symptoms presented with 2- to 3-week loss of scalp hair. Examination of the scalp revealed 90% of the hairs to be broken off, leaving a stubble of hairs less than 1 mm in length. Microscopically, plucked hairs demonstrated flattening, twisting through 180 degrees on its own axis, and breakage at the point of twisting. A diagnosis of pili torti was established. Pili torti is a rare disorder that may be seen with some genetic syndromes. Its association with citrullinemia has not been reported previously.

An acquired form of epidermolysis bullosa without immunoreactants: Report of a case

A patient with a 10-year history of an acquired, scarring bullous eruption localized to the anterior surfaces of the lower extremities is described. Clinical, histologic, and electron microscopic features of an acquired form of epidermolysis bullosa are shown to occur in the absence of immune deposits, a finding not previously documented.

Elevated thymosin alpha I levels in Brazilian pemphigus foliaceus.

Levels of thymosin alpha I in the sera of 37 patients with Brazilian pemphigus foliaceus (BPF) were measured using a competitive binding radioimmunoassay. The values were compared with 19 patients with other forms of pemphigus, 13 relatives of patients with BPF, 18 patients with other dermatological diseases, and 265 normal controls. We found that 27 (73%) of the patients with BPF had thymosin alpha I serum levels that were at least two standard deviations above the mean for normal individuals. The mean value for patients with BPF was significantly greater than any other groups studied. The thymosin elevation is similar to alterations seen in certain viral diseases and suggests that BPF is aetiopathogenically distinct from the other forms of pemphigus.

Human pemphigus autoantibodies are pathogenic to squamous epithelium

In 1957, Witbesky et al. put forward several criteria that ideally should be fulfilled in order to prove the pathogenic role of an autoantibody in a putative autoimmune disease. There can now be very little doubt of the autoimmune nature of this disease and of the primary role of autoantibodies in its pathogenesis. The evidence that supports the concept that pemphigus autoantibodies are of primary pathogenic importance in the disease is as follows: IgG class autoantibodies can be found both circulating in the serum and bound to the epithelial cell surfaces in and around lesions in patients with pemphigus. These autoantibodies, purified from the serum of pemphigus patients, can induce acantholytic lesions typical of pemphigus both in experimental animals (neonatal mice) and in human and murine epidermal cell cultures. These autoantibodies react with a specific antigen of the epidermal cell. This purified antigen has been used to immunize rabbits and the resulting antibodies are capable of inducing pemphigus-like lesions in neonatal mice.

Epidermal proteins. I. Differential extraction and quantitative polyacrylamide gel-electrophoretic analysis of basal spinous-cell proteins of neonatal mouse epidermis

SummaryThe study of keratinocyte proteins and their changes in different physiological, experimental, and pathological states has been facilitated and stimulated by the development of high-resolution polyacrylamide gel electrophoretic (PAGE) techniques. We describe a differential extraction system that separates the keratinocyte proteins into four major groups which are further quantitatively analyzed by PAGE: (1) cytoplasmic-soluble proteins, (2) nonionic-detergentsoluble proteins consisting of membrane-associated protein, (3) salt-dissociated proteins mainly consisting of histones, and ribosomal and keratohyaline granule proteins, and (4) the keratins (and other intermediate-filament-associated proteins), which are further separated into disulfide-stabilized keratins and keratins that do not require reducing agents in order to dissolve in sodium dodecyl sulfate (SDS) or urea. This extraction system was applied to neonatal mouse epidermal cell preparations that consisted mainly (60%–85%) of basal cells and also of some spinous cells (10%–30%). The SDS-PAGE patterns obtained by spectrophotometric scanning were graphically compared and integrated using an IBM personal computer. The protein bands in each extract were identified by their apparent molecular weights and were quantitated as a percentage of the total in each extract and in micrograms per 15×106 cells. Some protein peaks were provisionally identified as actin, the core histones H2A, H2B, H3, and H4, ribosomal proteins, and six keratins. This study serves as the foundation for the quantitative description of molecular changes which occur during keratinocyte differentiation and for the comprehensive identification of epidermal proteins.

The pemphigus antigens

Abstract Pemphigus antigens are normal squamous epithelial tissue constituents that are identified by their reaction with autoantibodies found in the serum of patients with active pemphigus vulgaris or any of the other types of pemphigus ( i.e. , vegetans, erythematosus, and foliaceous). The characteristic lesion of pemphigus is epidermal suprabasilar cell-cell detachment (acantholysis). It is important to note that pemphigus antigens are present in the intercellular substance (ICS) of stratified squamous epithelia where this process of acantholysis occurs. There is increasing evidence that pemphigus antigens are heterogenous, but whether this heterogeneity is due to the existence of different antigen molecules or different antigenic determinants on the same molecule is not yet clear. The use of the word antigens in this article does not imply commitment or rejection of any of these alternative explanations.