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Background: Immunofluorescence (IF) is a reliable biochemical staining technique for the detection of antibodies, which are bound to antigen in the tissue or circulating in body fluids. The relative simplicity and accuracy of the technique has made immunofluorescence an unavoidably powerful technique in the diagnosis of bullous diseases. Objectives: To detect the pattern of direct immunofluorescence (DIF) in the diagnosis of pemphigus. Methods: Thirty-six patients with pemphigus disease were enrolled in our study. The age of whom ranged from 21to 73 years with a mean age ± SD of 46.94±14.6 years Two skin biopsies (one from the bullous lesion and the other one from adjacent area) were taken from each patient, lesional biopsy specimens were used for histopathological examination after standard processing, while perilesional skin samples were used for performing direct immunofluorescence. Results: DIF was positive in all patients with pemphigus vulgaris (PV), showing intraepidermal deposition of immunoglobulins and complement 3 (C3). IgG was seen in all of them (100%), while C3 was also observed in 38.4% patients, and IgM was positive in (3.8%) in a similar pattern. Conclusion: Immunofluorescence (IF) studies are an important part of the laboratory evaluation of immunologically mediated bullous dermatoses and have become standard procedures for accurately diagnosing patients with these disorders.

Background: Immunofluorescence (IF) is a reliable biochemical staining technique for the detection of antibodies, which are bound to antigen in the tissue or circulating in body fluids. The relative simplicity and accuracy of the technique has made immunofluorescence an unavoidably powerful technique in the diagnosis of bullous diseases. Objectives: To detect the pattern of direct immunofluorescence (DIF) in the diagnosis of pemphigus. Methods: Thirty-six patients with pemphigus disease were enrolled in our study. The age of whom ranged from 21to 73 years with a mean age ± SD of 46.94±14.6 years Two skin biopsies (one from the bullous lesion and the other one from adjacent area) were taken from each patient, lesional biopsy specimens were used for histopathological examination after standard processing, while perilesional skin samples were used for performing direct immunofluorescence. Results: DIF was positive in all patients with pemphigus vulgaris (PV), showing intraepidermal deposition of immunoglobulins and complement 3 (C3). IgG was seen in all of them (100%), while C3 was also observed in 38.4% patients, and IgM was positive in (3.8%) in a similar pattern. Conclusion: Immunofluorescence (IF) studies are an important part of the laboratory evaluation of immunologically mediated bullous dermatoses and have become standard procedures for accurately diagnosing patients with these disorders.

Background: Immunofluorescence (IF) is a reliable biochemical staining technique for the detection of antibodies, which are bound to antigen in the tissue or circulating in body fluids. The relative simplicity and accuracy of the technique has made immunofluorescence an unavoidably powerful technique in the diagnosis of bullous diseases. Objectives: To detect the pattern of direct immunofluorescence (DIF) in the diagnosis of pemphigus. Methods: Thirty-six patients with pemphigus disease were enrolled in our study. The age of whom ranged from 21to 73 years with a mean age ± SD of 46.94±14.6 years Two skin biopsies (one from the bullous lesion and the other one from adjacent area) were taken from each patient, lesional biopsy specimens were used for histopathological examination after standard processing, while perilesional skin samples were used for performing direct immunofluorescence. Results: DIF was positive in all patients with pemphigus vulgaris (PV), showing intraepidermal deposition of immunoglobulins and complement 3 (C3). IgG was seen in all of them (100%), while C3 was also observed in 38.4% patients, and IgM was positive in (3.8%) in a similar pattern. Conclusion: Immunofluorescence (IF) studies are an important part of the laboratory evaluation of immunologically mediated bullous dermatoses and have become standard procedures for accurately diagnosing patients with these disorders.

The aim of this study was to evaluate the diagnostic value of Dsg1 and 3 enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pemphigus. Thirty-six patients with pemphigus were enrolled. The diagnosis was confirmed by histopathology and direct immunofluorescence (DIF). Autoantibodies against Dsg1, and Dsg3 were assayed, by ELISA, in serum of pemphigus patients. In pemphigus vulgaris (PV), anti-Dsg1 and anti-Dsg 3 antibodies titre were raised above the cut off value in 88.5% and 96.1% of patients respectively. Dsg-3 was more sensitive than Dsg-1(96.2% versus 88.5%) while both have the same specificity 95%. In PF and PH, the only anti-Dsg-1 level was raised in all cases (100%). Conclusion: In PV Dsg-3 was more sensitive than Dsg-1while in pemphigus foliaceous and pemphigus herpetiformis, only anti-Dsg-1 was detected in all cases (100%). Both anti-Dsg1Ab and anti-Dsg3Ab ELISA values are correlated with the disease activity.

The aim of this study was to evaluate the diagnostic value of Dsg1 and 3 enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pemphigus. Thirty-six patients with pemphigus were enrolled. The diagnosis was confirmed by histopathology and direct immunofluorescence (DIF). Autoantibodies against Dsg1, and Dsg3 were assayed, by ELISA, in serum of pemphigus patients. In pemphigus vulgaris (PV), anti-Dsg1 and anti-Dsg 3 antibodies titre were raised above the cut off value in 88.5% and 96.1% of patients respectively. Dsg-3 was more sensitive than Dsg-1(96.2% versus 88.5%) while both have the same specificity 95%. In PF and PH, the only anti-Dsg-1 level was raised in all cases (100%). Conclusion: In PV Dsg-3 was more sensitive than Dsg-1while in pemphigus foliaceous and pemphigus herpetiformis, only anti-Dsg-1 was detected in all cases (100%). Both anti-Dsg1Ab and anti-Dsg3Ab ELISA values are correlated with the disease activity.

The aim of this study was to evaluate the diagnostic value of Dsg1 and 3 enzyme-linked immunosorbent assay (ELISA) in the diagnosis of pemphigus. Thirty-six patients with pemphigus were enrolled. The diagnosis was confirmed by histopathology and direct immunofluorescence (DIF). Autoantibodies against Dsg1, and Dsg3 were assayed, by ELISA, in serum of pemphigus patients. In pemphigus vulgaris (PV), anti-Dsg1 and anti-Dsg 3 antibodies titre were raised above the cut off value in 88.5% and 96.1% of patients respectively. Dsg-3 was more sensitive than Dsg-1(96.2% versus 88.5%) while both have the same specificity 95%. In PF and PH, the only anti-Dsg-1 level was raised in all cases (100%). Conclusion: In PV Dsg-3 was more sensitive than Dsg-1while in pemphigus foliaceous and pemphigus herpetiformis, only anti-Dsg-1 was detected in all cases (100%). Both anti-Dsg1Ab and anti-Dsg3Ab ELISA values are correlated with the disease activity.

While clinical benefit of the proteasome inhibitor (PI) bortezomib (BTZ) for multiple myeloma (MM) patients remains unchallenged, dose-limiting toxicities and drug resistance limit the long-term utility. The E3 ubiquitin ligase Skp1–Cullin-1–Skp2 (SCFSkp2) promotes proteasomal degradation of the cell cycle inhibitor p27 to enhance tumor growth. Increased SKP2 expression and reduced p27 levels are frequent in human cancers and are associated with therapeutic resistance. SCFSkp2 activity is increased by the Cullin-1-binding protein Commd1 and the Skp2-binding protein Cks1B. Here we observed higher CUL1, COMMD1 and SKP2 mRNA levels in CD138+ cells isolated from BTZ-resistant MM patients. Higher CUL1, COMMD1, SKP2 and CKS1B mRNA levels in patient CD138+ cells correlated with decreased progression-free and overall survival. Genetic knockdown of CUL1, COMMD1 or SKP2 disrupted the SCFSkp2 complex, stabilized p27 and increased the number of annexin-V-positive cells after BTZ treatment. Chemical library screens identified a novel compound, designated DT204, that reduced Skp2 binding to Cullin-1 and Commd1, and synergistically enhanced BTZ-induced apoptosis. DT204 co-treatment with BTZ overcame drug resistance and reduced the in vivo growth of myeloma tumors in murine models with survival benefit. Taken together, the results provide proof of concept for rationally designed drug combinations that incorporate SCFSkp2 inhibitors to treat BTZ resistant disease.

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