Altered Morphology and Distribution of Cellular Junction Proteins in Non-Lesional Psoriatic Epidermis: An Insight into Disease Severity

BackgroundPsoriasis affects 2.7% of the world's population. Keratinocyte proliferation outside the basal layer suggests alterations in cell–cell interactions in affected epidermis. Anomalous expression of proteins forming intercellular junctions has been reported in lesional skin of psoriatic patients. In contrast, little is known about possible alterations in psoriatic non-lesional skin.MethodsTen clinically diagnosed psoriasis vulgaris patients and ten controls were studied. All patients were diagnosed with active but controlled psoriatic plates (PASI 3 to 5) and had not received any systemic treatment. The mean age was 43 years for patients and 43.5 years for controls. Four-mm2 skin samples were taken from lesional and non-lesional zones in patients and from abdomen in controls. Five-μm sections were examined for integrity and structural organization by fluorescent labeling of actin filaments and nuclei. Specific antibodies were utilized to localize occludin, E-cadherin, β-catenin, and proliferation-specific keratins in sections and epidermal sheets. Samples were also processed for immunoblotting with occludin antibody.ResultsLesional and non-lesional psoriatic epidermis from all patients showed keratinocyte hyperproliferation, lack of rete ridges and dermal papillae in the dermal-epidermal junction in some areas. Proteins forming tight and adherens junctions in non-lesional skin keratinocytes from two patients who during the course of the study evolved to uncontrolled disease, showed similar alterations to those observed in lesional skin of all the patients. However, the occludin isoforms expressed were apparently the same in all samples.ConclusionsAnalysis of non-lesional skin in psoriatic patients diagnosed with controlled disease may provide clues about incipient structural abnormalities in the pathogenesis of psoriasis, providing an early diagnostic indicator for evolution to a generalized form of the disease.