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Razzaque A Ahmed - One of the best experts on this subject based on the ideXlab platform.
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Role of Enhanced Expression of m-CSF in Conjunctiva Affected by Cicatricial Pemphigoid
2013Co-Authors: Mohammed S Razzaque, Stephen C Foster, Razzaque A AhmedAbstract:PURPOSE. Local proliferation of macrophages has been reported to augment the inflammatory response in various human and experimental diseases. Macrophage accumulation in the submucosa is also an important feature in the pathogenesis of ocular Cicatricial Pemphigoid (OCP). In the present study, the role of local proliferation of macrophages in conjunctiva affected by OCP and the relationship between local proliferation of macrophages and expression of macrophage-colony-stimulating factor (m-CSF) in such conjunctiva were examined. METHODS. Biopsy specimens from the conjunctiva of 10 untreated patients with active OCP and from 5 normal subjects were studied for the expression of m-CSF, macrophages, and proliferating cell nuclear antigen (PCNA), a cell cycle protein, by immunohistochemistry. Dual staining for CD68 (a cell surface marker for macrophages) and PCNA was also performe
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combination of rituximab and intravenous immunoglobulin for recalcitrant ocular Cicatricial Pemphigoid a preliminary report
Ophthalmology, 2010Co-Authors: Stephen C Foster, Peter Y Chang, Razzaque A AhmedAbstract:Purpose To compare the effectiveness and safety of the combination therapy of rituximab (RTX) and intravenous immunoglobulin (IVIg) to other immunosuppressive regimens in the treatment of ocular Cicatricial Pemphigoid (OCP). Design Retrospective, comparative, interventional case series. Participants Twelve patients with OCP. Methods We reviewed medical records of 12 patients with OCP. Ten of the 12 patients were blind in 1 eye after initial systemic immunosuppressive therapies (phase 1 treatment). The patients were then divided into 2 groups based on treatments received during phase 2. The study group consisted of 6 patients who received the combination of RTX and IVIg during phase 2 of their treatment. For comparison purposes, the control group consisted of 6 patients who during phase 2 of their treatment received more aggressive immunosuppressive therapies, but not RTX and IVIg, because the insurance carriers refused to pay for the combination therapy. Main Outcome Measures Blindness (best-corrected visual acuity [BCVA] ≤20/200) and OCP staging (Foster). Results The median total follow-up periods were 57.5 and 55.5 months in the control group and the study group, respectively. After phase 1 treatment, all 6 patients in the control group were blind in 1 eye. Similarly, 4 of the patients in the study group were blind in 1 eye, whereas 2 had good BCVA bilaterally but experienced persistent conjunctival inflammation despite phase 1 treatment. After phase 2 treatment, all 6 patients in the control group had OCP progression and became blind in both eyes. In contrast, BCVA was stable and no further progression of OCP staging was observed in all 6 patients in the study group. In the study group, the median follow-up from completion of the RTX and IVIg treatment protocol was 11 months. No adverse events, immediate or delayed, were reported in any of the patients who received the combination therapy of RTX and IVIg. Conclusions In this preliminary study, the combination therapy of RTX and IVIg arrested disease progression and prevented total blindness in patients with recalcitrant OCP. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.
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antigen specificity in subsets of mucous membrane Pemphigoid
Journal of Investigative Dermatology, 2006Co-Authors: Khwaja Aftab Rashid, Haka M Gurca, Razzaque A AhmedAbstract:Mucous membrane Pemphigoid (MMP) has several subsets based on target antigens recognized by their sera. MMP and ocular Cicatricial Pemphigoid (OCP) sera recognize β4 integrin subunit, oral Pemphigoid sera recognize α6 integrin subunit, and anti-epiligrin Cicatricial Pemphigoid sera recognize laminin 5. Our aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and oral Pemphigoid (OP) recognize only their target antigens, and to see if this specificity is maintained throughout the clinical course. An immunoblot assay using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight with OCP, and 15 OP patients were studied before therapy and at multiple intervals during the clinical course. Absorption and blocking studies were performed to determine binding specificity. Sera of patients with MMP and OCP recognize only β4 integrin subunit, and sera of OP patients recognize α6 integrin throughout the clinical course. The sera of patients in the subsets of MMP described in this report show adherence and selectivity to target antigen during the entire clinical course, without crossover, interaction, or change. Hence, these subsets of MMP provide an excellent model to study clinical correlation with antigen and antibody specificity, in autoimmunity.
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a nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane Cicatricial Pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies
Clinical Immunology, 2004Co-Authors: Erik Letko, Stephe C Foste, Razzaque A Ahmed, Elisabetta Miserocchi, Yassine J Daoud, William G ChristeAbstract:The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane Pemphigoid (MMP), also known as Cicatricial Pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular Cicatricial Pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1) presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2) entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3) presence of conventional immunosuppressive therapy at the time of ocular involvement; (4) a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16–30) in group A and 45 months (range 21–90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0–4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0–1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.
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role of collagen binding heat shock protein 47 and transforming growth factor β1 in conjunctival scarring in ocular Cicatricial Pemphigoid
Investigative Ophthalmology & Visual Science, 2003Co-Authors: Mohammed S Razzaque, Stephen C Foster, Razzaque A AhmedAbstract:PURPOSE. Submucosal fibrosis due to excessive accumulation of collagens is an important histologic feature in the pathogenesis of ocular Cicatricial Pemphigoid (OCP). Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the biosynthesis of procollagens. In the present study, we examined the role of HSP47 in conjunctival scarring in patients with OCP. METHODS. Biopsy specimens of the conjunctiva of 15 patients with OCP and 5 normal subjects were studied for the expression of HSP47, transforming growth factor (TGF)-1, type I collagen, and type III collagen. The role of TGF- 1o n the induction of HSP47 and type I collagen by conjunctival fibroblasts was studied by immunostaining, Western blot analysis, and quantitative real-time PCR. RESULTS. Compared with the control, increased accumulations of type I and type III collagens were detected by immunohistochemistry in fibrotic conjunctiva of patients with OCP. Weak and sparse expression of HSP47 was detected in the epithelial cells and stromal fibroblasts in control conjunctival tissues. In contrast to the control, the expression of HSP47 was markedly increased in the stromal fibroblasts in conjunctival tissues obtained from patients with OCP, as detected by immunohistochemistry. By quantitative real-time PCR, compared with control conjunctival tissues, a 3.4-fold increase in the expression of HSP47 was noted in the conjunctival tissues obtained from patients with OCP. Similar to conjunctival tissues, fibroblasts isolated from conjunctiva of patients with OCP exhibited 4.8fold increase in the expression of HSP47, compared with control fibroblasts. When conjunctival fibroblasts were treated with various concentration of TGF-1, upregulation in the expression of HSP47 and type I collagen was detected. CONCLUSIONS. This study demonstrated increased expression of HSP47 and TGF-1 by conjunctival fibroblasts in biopsy specimens obtained from patients with OCP. TGF-1 induced the expression of HSP47 and type I collagen by conjunctival fibroblasts. Increased levels of TGF-1 and HSP47 may regulate increased synthesis, assembly, and production of collagens and thereby could significantly contribute to the process of conjunctival scarring in patients with OCP. (Invest Ophthalmol
Stephen C Foster - One of the best experts on this subject based on the ideXlab platform.
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Profile of Local Interleukin Expression in a Cohort of Ocular Cicatricial Pemphigoid Patients
2020Co-Authors: Ana M Suelves, Tong Z Zhao, Sana S Siddique, Stephen C FosterAbstract:PURPOSE. We investigated the expression of IL-1, IL-6, IL-12, IL-13, and IL-17 in the conjunctiva of patients with ocular Cicatricial Pemphigoid (OCP), also labeled as ocular mucous membrane Pemphigoid (MMP). METHODS. A retrospective case-control study was done on 5 biopsy-proven OCP subjects and 6 healthy volunteers. Conjunctival specimens were obtained, and the local expression of IL-1, IL-6, IL-12, IL-13, and IL-17 was studied by immunohistochemistry. Clinical and therapeutic features were collected during follow-up. RESULTS. No remarkable IL-1, IL-6, IL-12, IL-13, or IL-17 expression was observed in normal conjunctival specimens. All OCP samples had remarkable amounts of IL-12 and IL-17 expression especially in the epithelium and stroma; there also was stromal overexpression of IL-6. The mean follow-up after the biopsy was 13 months (range 9-15 months). CONCLUSIONS. Our results demonstrated, for the first time to our knowledge, a local overexpression of IL-6, IL-12, and IL-17 in conjunctiva of OCP compared to controls. (Invest Ophthalmol Vis Sci. 2012;53:8112-8117
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management of ocular Cicatricial Pemphigoid with intravenous immunoglobulin monotherapy
Ocular Immunology and Inflammation, 2019Co-Authors: Caiyun You, Mikhail Hernandez, Arash Maleki, Andres F Lasave, Alexander Schmidt, Andrew Stephenson, Thongzen Zhao, Stephen D Anesi, Stephen C FosterAbstract:Purpose: To assess the long-term efficacy and safety of IVIg monotherapy in patients with recalcitrant ocular Cicatricial Pemphigoid (OCP). Methods: A chart review of all OCP patients seen at the Massachusetts Eye Research and Surgery Institution (MERSI) between 2005 and 2015 was completed. Stage was graded by using the Foster grading system. IVIg infusion was 2g/kg/cycle administered in 3 consecutive days monthly. Results: Of 512 OCP patients, 17 patients (34 eyes) treated with IVIg monotherapy were identified. Seven were female and ten were male. The average age at diagnosis was 60.7-year-old. The follow up time ranged from 12 to 140 months. Twenty-six eyes (76.5%) achieved remission. Nine remission eyes received cataract surgeries, and 2 of them had relapse (22.2%). The other 17 eyes did not undergo ocular surgery and remained in remission. IVIg monotherapy showed high efficacy in stage 1 OCP (7/7, 100%). Ocular surgery can be associated with OCP relapse (Table 2). Conclusions: IVIg monotherapy is an effective and safe therapy in patients with recalcitrant OCP. Ocular surgery can be associated with OCP relapse.
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long term remission of ocular Cicatricial Pemphigoid off immunomodulatory therapy
European Journal of Ophthalmology, 2018Co-Authors: Caiyun You, Stephen D Anesi, Stephen C FosterAbstract:Purpose To evaluate whether long-term remission of ocular Cicatricial Pemphigoid (OCP) after withdrawal of immunomodulatory therapy (IMT) is possible. Methods A total of 34 of 464 presenting patients (66 eyes) with biopsy-proven OCP in long-term remission off IMT were identified after finishing a 2-year IMT regimen without active disease (2005-2015). Long-term remission off IMT for OCP was defined as patients withdrawn from IMT ≥1 year lacking clinically detectable progressive scarring according to Foster staging and subjective assessment. Results All 34 patients achieved ≥1 year of clinical remission without IMT following 2 years IMT lacking active disease. Mean onset age of OCP was 67.0 years, and median follow-up time was 63.4 months. Mean duration between OCP onset and IMT initiation was 29.5 months, with a mean sustained remission time of 36.0 months off IMT. The mean duration of IMT prior to remission off IMT was 34.8 months (median 32 months, IQR 27-39.5 months). Commonly, methotrexate was used prior to OCP remission (19 patients; 55.9%). Two patients experienced mild flare-up postremission off IMT at months 25 and 37 and a course of topical steroid appeared to resolve the inflammation. Another patient had active inflammation at last office visit 5 years after discontinuation of IMT and will restart IMT. Conclusions Long-term remission for OCP off IMT may be achieved after stepladder IMT is implemented and withdrawn. Longer follow-up and more sensitive measures of scarring and inflammation are needed to generate a consensus on the definition of complete remission and on cessation of systemic IMT for OCP.
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rituximab in the treatment of ocular Cicatricial Pemphigoid a retrospective cohort study
Graefes Archive for Clinical and Experimental Ophthalmology, 2017Co-Authors: Caiyun You, Neerav Lamba, Andres F Lasave, Mikhail Hernandez Diaz, Stephen C FosterAbstract:The purpose was to evaluate the effectiveness and safety of rituximab (RTX) for the treatment of patients with aggressive ocular Cicatricial Pemphigoid (OCP). A review of patient records at a tertiary referral center with biopsy confirmed OCP who presented between 2006 and 2016. Sixty-one eyes of 32 patients with symptomatic OCP who received treatment with RTX monotherapy or RTX in combination with additional immunomodulatory treatment (IMT) were evaluated. Main outcomes included clinically evident remission of disease, the percentage of corticosteroid sparing patients, stage of OCP (Foster), best corrected visual acuity, and treatment complications. Remission was defined as absence of progressive scarring and active ocular inflammation for ≥ 2 months. Partial remission/responding was defined as disease control and clinical improvement for ≥ 2 months. Mean age at the initiation of RTX treatment was 59.1 years (range, 24–80 years) with a median follow-up time after RTX initiation of 32 months (range, 14 to 127 months). Twenty-six patients achieved clinical remission with an average sustained remission of 24.5 months (from 9 months to 84 months). RTX monotherapy was used in six patients, RTX in combination with intravenous immunoglobulin in 14 patients, and RTX with intravenous immunoglobulin and/or with other IMT agent in six patients. Seven eyes (11.5%) of six patients had favorable response to RTX and achieved response and partial remission, while inflammation remained active in the other seven eyes (11.5%) of four patients though there was no progressive scarring. At the last visit, three patients (9.4%) were on topical corticosteroid, three patients (9.4%) were treated with systemic corticosteroid treatments, and the other 26 patients (81.2%) achieved corticosteroid sparing therapy. Five eyes (8.2%) progressed one Foster stage. No other cicatrization progression or worsening of LogMAR visual acuity (p = 0.641) was observed during the follow-up period. Adverse events included leukopenia in three patients (9.4%), anemia in two patients (6.2%), liver enzyme elevation in three patients (9.4%) who were also on another concomitant IMT drug, and Epstein-Barr Virus infection and sinus infection in one patient each (3.1%). No other severe adverse events were noted during the follow-up period. These retrospective data suggest that RTX is efficacious and well tolerated when included for the treatment of OCP. Controlled studies are necessary to identify the role of this IMT agent in the therapeutic arsenal, especially its optimum dose and duration of administration.
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neutrophil collagenase gelatinase and myeloperoxidase in tears of patients with stevens johnson syndrome and ocular Cicatricial Pemphigoid
Ophthalmology, 2014Co-Authors: Samer N Arafat, Stephen C Foster, Ana M Suelves, Sandra Spurrmichaud, James Chodosh, Claes H Dohlman, Ilene K GipsonAbstract:Objective To investigate the levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in tears of patients with Stevens-Johnson syndrome (SJS) and ocular Cicatricial Pemphigoid (OCP). Design Prospective, noninterventional cohort study. Participants Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20 healthy controls who underwent phacoemulsification (40 eyes). Methods Tear washes were collected from all patients and were analyzed for levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based enzyme-linked immunosorbent assays. Total MMP activity was determined using a fluorometric assay. Correlation studies were performed between the various analytes within study groups. Main Outcome Measures Levels of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein) and total MMP activity (in relative fluorescent units per minute per microgram of protein) in tears; MMP-8–to–TIMP-1 ratio; MMP-9–to–TIMP-1 ratio; and the correlations between MMP-8 and MMP-9 and both MMP and MPO. Results MMP-8, MMP-9, and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when compared with controls. The MMP activity was highest in SJS patients, whereas OCP patients and controls showed lower and similar activities. The TIMP-1 levels were decreased in SJS and OCP patients when compared with those in controls, with levels in OCP patients reaching significance. The MMP-8–to–TIMP-1 and MMP-9–to–TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared with those of controls. Across all study groups, MMP-9 levels correlated strongly with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach significance in SJS patients. There was no relationship between MMP-7 and MPO. Conclusions Because MMP-8 and MPO are produced by inflammatory cells, particularly neutrophils, the correlation data indicate that they may be the common source of elevated enzymes, including MMP-9, in SJS and OCP tears. Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP regulation that may explain the predisposition of these patients to demonstrate corneal melting and chronic complications associated with persistent inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for the quantification of ocular inflammation.
A R Ahmed - One of the best experts on this subject based on the ideXlab platform.
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collagens collagen binding heat shock protein 47 and transforming growth factor β1 are induced in Cicatricial Pemphigoid possible role s in dermal fibrosis
Cytokine, 2002Co-Authors: Mohammed S Razzaque, A R AhmedAbstract:Cicatricial Pemphigoid (CP) is an autoimmune mucocutaneous blistering disease associated with scarring. Heat shock protein 47 (HSP47) is thought to play an important role in fibrogenesis, but its role in skin lesions of Cicatricial Pemphigoid is not yet known. In the present study, we examined the role of HSP47 in dermal fibrosis in cutaneous lesions of a CP patient. Skin biopsies from a patient with CP, and from normal subjects were studied for the expression of HSP47, and interstitial collagens (type I and type III collagens) by immunohistochemistry. Dermal fibroblasts isolated from skin of normal individuals and from fibrotic skin of a CP patient were used to study the expression of HSP47, transforming growth factor β1 (TGF-β1), type I and type III collagens. Compared to the control skin sections, an increased expression of HSP47 was associated with an increased deposition of interstitial collagens in the fibrotic skin section of the CP patient. Similarly, in contrast to control dermal fibroblasts, the fibroblasts isolated and cultured from fibrotic skin of the CP patient, and grown in vitro, exhibited increased expression of HSP47, type I and type III collagens. Furthermore, compared to the normal control fibroblasts, an increased expression of TGF-β1 was detected in the dermal fibroblasts isolated from fibrotic skin of the CP patient. When dermal fibroblasts were treated with various concentrations of TGF-β1 (6.25, 12.5, 25, 50 and 100 ng/ml for 24 h), it induced the expression of both type I collagen and HSP47, as determined by quantitative real-time PCR. In conclusion, the expression of TGF-β1, HSP47, type I collagen and type III collagen was up-regulated in the fibrotic skin of CP patient, and a complex interaction of these molecules may initiate and propagate the fibrotic cascade in the skin of CP patients.
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Cicatricial Pemphigoid with circulating autoantibodies to beta 4 integrin, bullous Pemphigoid 180 and bullous Pemphigoid 230
2001Co-Authors: Leverkus M, A R Ahmed, Bhol K., Hirako Y, Pas H, Sitaru C, Baier G, Eb Brocker, Mf Jonkman, Zillikens DAbstract:Cicatricial Pemphigoid is a heterogeneous group of autoimmune subepidermal blistering diseases associated most commonly with autoantibodies to bullous Pemphigoid (BP)180 and less frequently with those to laminin 5 or type VII collagen. In addition. a few cases have been described with autoantibodies to the beta4 subunit of alpha6beta4 integrin. We describe a patient with extensive disease of ocular. oral, pharyngeal. laryngeal and genital mucous membranes that healed with scarring of conjunctivae. IgG autoantibodies bound to the dermal-epidermal junction on direct immunofluorescence (IF) microscopy and to the epidermal side of 1 mol L-1 NaCl-split skin on indirect IF microscopy. Our patient's circulating IgG recognized a 205-kDa protein in extracts of 293T cells transfected with the beta4 subunit of alpha6beta4 integrin and in the cell extract of DJM-1 cells. Our patient's IgG and IgA autoantibodies also reacted with full-length BP180 derived from epidermal extracts and the ectodomain of BP180 (LAD-1) derived from culture supernatant of keratinocytes. In addition. a weak IgG reaction with BP230 was noted. The disease rapidly responded to dexamethasone-cyclophosphamide pulse therapy, and immunoblot reactivity to both beta4 integrin and BP180 decreased according to disease activity
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the role of antibody to human β4 integrin in conjunctival basement membrane separation possible in vitro model for ocular Cicatricial Pemphigoid
Investigative Ophthalmology & Visual Science, 1999Co-Authors: Robert K Y Chan, Kailash C Bhol, C S Foster, Erik Letko, N Tesavibul, R K Simmons, A R AhmedAbstract:Purpose To demonstrate the specific binding of autoantibodies present in the sera of patients with ocular Cicatricial Pemphigoid (OCP) to human beta4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human beta4 integrin in the pathogenesis of subepithelial lesion formation in OCP. Methods Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human beta4, beta1, alpha6, and alpha5 integrins; and sera from patients with pemphigus vulgaris, bullous Pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used. Results Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human beta4 and alpha6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-beta4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the beta4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-beta4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission. Conclusion Circulating anti-beta4 integrin antibody may have an important role in the pathogenesis of OCP.
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ocular Cicatricial Pemphigoid antigen partial sequence and biochemical characterization
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Shivraj Tyagi, Kailash C Bhol, K Natarajan, C Livirrallatos, C S Foster, A R AhmedAbstract:Ocular Cicatricial Pemphigoid (OCP) is an autoimmune disease that affects mainly conjunctiva and other squamous epithelia. OCP is histologically characterized by a separation of the epithelium from underlying tissues within the basement membrane zone. Immunopathological studies demonstrate the deposition of anti-basement membrane zone autoantibodies in vivo. Purified IgG from sera of patients with active OCP identified a cDNA clone from a human keratinocyte cDNA library that had complete homology with the cytoplasmic domain of β4-integrin. The sera recognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as β4-integrin by its reaction with polyclonal and monoclonal antibodies to human β4-integrin. Sera from patients with bullous Pemphigoid, pemphigus vulgaris, and Cicatricial Pemphigoid-like diseases did not recognize the 205-kDa protein, indicating the specificity of the binding. These data strongly implicate a role for human β4-integrin in the pathogenesis of OCP. It should be emphasized that multiple antigens in the basement membrane zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases. Molecular definition of these autoantigens will facilitate the classification and characterization of subsets of Cicatricial Pemphigoid and help distinguishing them from bullous Pemphigoid. This study highlights the function and importance of β4-integrin in maintaining the attachment of epithelial cells to the basement membrane.
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differences in the anti basement membrane zone antibodies in ocular and pseudo ocular Cicatricial Pemphigoid
Current Eye Research, 1996Co-Authors: Kailash C Bhol, A Mohimen, Ron Neumann, Juan J Yunis, S Foster, Edmond J Yunis, A R AhmedAbstract:Purpose. Ocular Cicatricial Pemphigoid (OCP) is a chronic autoimmune cicatrizing disease which affects the conjunctiva and other squamous epithelium, resulting in a scarring process. A similar process, limited only to the conjunctiva, observed in some patients using eye drops for the treatment of glaucoma, is called pseudo-ocular Cicatricial Pemphigoid (P-OCP). Im-munofluorescence studies demonstrate deposition of immuno-globulins and complement components in the basement membrane zone (BMZ) of the conjunctiva and an anti-basement membrane zone antibody in the serum of patients. A striking association between OCP and MHC class II gene DQBl*0301 has been observed. The purpose of this study was to determine some of the differences in the binding of OCP and P-OCP sera to different lysate in an immunoblot assay, in an attempt to partially characterize the OCP and P-OCP antigens. Furthermore, we wanted to determine if the MHC class II gene association of P-OCP is similar to that of OCP.Methods. We studied sera...
Kim B Yancey - One of the best experts on this subject based on the ideXlab platform.
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Anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita: Differentiation by use of indirect immunofluorescence microscopy
Journal of the American Academy of Dermatology, 2003Co-Authors: Robert M. Vodegel, Kim B Yancey, Marcelus C.j.m. De Jong, Hendri H. Pas, Marcel F. JonkmanAbstract:Abstract Binding of autoantibodies to laminin 5 and type VII collagen causes anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita, respectively. Differentiation between these two dermal-binding autoimmune bullous dermatoses is not yet possible by indirect immunofluorescence microscopy. In this study we tested whether two recently described immunofluorescence techniques, "knockout" skin substrate and fluorescent overlay antigen mapping, can differentiate between anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita. A total of 10 sera were tested: 4 with antilaminin 5, and 6 with antitype VII collagen autoantibodies, as characterized by either immunoblot or immunoprecipitation analysis. Differentiation between anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita was possible in all 10 sera by indirect immunofluorescence using either knockout skin substrate or fluorescent overlay antigen mapping technique. (J Am Acad Dermatol 2003;48:542-7.)
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inflammatory variant of epidermolysis bullosa acquisita with igg autoantibodies against type vii collagen and laminin α3
Archives of Dermatology, 2000Co-Authors: Marcel F. Jonkman, Kim B Yancey, Marcelus C.j.m. De Jong, Jacqueline Schuur, F Dijk, K Heeres, Jan Van Der Meer, Hendri H. PasAbstract:Background: The inflammatory variant of epidermolysis bullosa acquisita (EBA) may clinically closely resemble bullous or Cicatricial Pemphigoid. Patients with inflammatory EBA have IgG autoantibodies against type VII collagen. Patients with anti-epiligrin Cicatricial Pemphigoid have IgG autoantibodies against laminin 5. Observation: We describe a patient with inflammatory EBA exhibiting nonscarring oral and vaginal involvement. Indirect immunofluorescence using skin substrate lacking an epidermal basement membrane molecule, direct immunoelectron microscopy, immuno-blot, and immunoprecipitation studies revealed the simultaneous presence of circulating IgG autoantibodies against type VII collagen and laminin alpha 3. A final diagnosis of EBA was based on the sublamina densa level of blister formation. Conclusion: This case illustrates the clinical and immunological overlap between EBA and anti-epiligrin Cicatricial Pemphigoid, a unique finding that may have developed as a consequence of epitope spreading.
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anti epiligrin Cicatricial Pemphigoid a case associated with gastric carcinoma and features resembling epidermolysis bullosa acquisita
British Journal of Dermatology, 1998Co-Authors: Wataru Fujimoto, Kim B Yancey, Akemi Ishidayamamoto, Roger Hsu, Y Nagao, Hajime Iizuka, Jiro ArataAbstract:A 48-year-old woman with anti-epiligrin Cicatricial Pemphigoid (CP) who showed clinical features resembling epidermolysis bullosa acquisita was found to have adenocarcinoma of the stomach. Histological examination of lesional skin demonstrated a subepidermal blister. Direct immunofluorescence microscopy of perilesional skin revealed linear deposits of IgG and C3 at the basement membrane zone. The patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal human skin as determined by indirect immunofluorescence microscopy, and the lamina lucida as determined by indirect immunoelectron microscopy. The patient's serum immunoprecipitated laminin-5 from extracts and media of biosynthetically radiolabelled human keratinocytes. Immunoblot studies showed that the patient's autoantibodies specifically bound the alpha3 subunit of this laminin isoform. Fragility of the skin and bullous lesions disappeared after total gastrectomy, but soon reappeared possibly in association with metastatic disease in a lymph node. The possibility that anti-epiligrin CP may develop paraneoplastically in some patients is discussed.
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analysis of antigens targeted by circulating igg and iga autoantibodies in 50 patients with Cicatricial Pemphigoid
Journal of Dermatological Science, 1998Co-Authors: Hector Murakami, Detlef Zillikens, Shoji Nishioka, Jane Setterfield, B S Bhogal, M M Black, Kim B Yancey, Shawn D BaldingAbstract:In this study we investigated sera from 50 typical Cicatricial Pemphigoid (CP) patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections, IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split, while IgG of two sera reacted with the dermal side. These latter two sera were later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts, IgG of 14 sera reacted with the 230 kD bullous Pemphigoid (BP) antigen (BP230). IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180). Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was recognized by IgG of 18 sera but not by IgA of any sera. Fusion proteins containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but it was detected by IgA of only two sera. Our results suggest that, although CP sera show very low titers of autoantibodies, a considerable number of sera contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming previous studies. In addition, we showed that greater numbers of IgA antibodies react with BP180, seemingly with different types of epitopes from those for IgG antibodies. Because the specificity of IgG antibodies is not very different from those in BP, IgA antibodies may play a specific role for the development of characteristic clinical features in CP. Future studies should elucidate the pathogenic role of the IgA antibodies in CP.
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Anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita: Differentiation by use of indirect immunofluorescence microscopy
Journal of the American Academy of Dermatology, 2003Co-Authors: Robert M. Vodegel, Kim B Yancey, Marcelus C.j.m. De Jong, Hendri H. Pas, Marcel F. JonkmanAbstract:Abstract Binding of autoantibodies to laminin 5 and type VII collagen causes anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita, respectively. Differentiation between these two dermal-binding autoimmune bullous dermatoses is not yet possible by indirect immunofluorescence microscopy. In this study we tested whether two recently described immunofluorescence techniques, "knockout" skin substrate and fluorescent overlay antigen mapping, can differentiate between anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita. A total of 10 sera were tested: 4 with antilaminin 5, and 6 with antitype VII collagen autoantibodies, as characterized by either immunoblot or immunoprecipitation analysis. Differentiation between anti-epiligrin Cicatricial Pemphigoid and epidermolysis bullosa acquisita was possible in all 10 sera by indirect immunofluorescence using either knockout skin substrate or fluorescent overlay antigen mapping technique. (J Am Acad Dermatol 2003;48:542-7.)
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inflammatory variant of epidermolysis bullosa acquisita with igg autoantibodies against type vii collagen and laminin α3
Archives of Dermatology, 2000Co-Authors: Marcel F. Jonkman, Kim B Yancey, Marcelus C.j.m. De Jong, Jacqueline Schuur, F Dijk, K Heeres, Jan Van Der Meer, Hendri H. PasAbstract:Background: The inflammatory variant of epidermolysis bullosa acquisita (EBA) may clinically closely resemble bullous or Cicatricial Pemphigoid. Patients with inflammatory EBA have IgG autoantibodies against type VII collagen. Patients with anti-epiligrin Cicatricial Pemphigoid have IgG autoantibodies against laminin 5. Observation: We describe a patient with inflammatory EBA exhibiting nonscarring oral and vaginal involvement. Indirect immunofluorescence using skin substrate lacking an epidermal basement membrane molecule, direct immunoelectron microscopy, immuno-blot, and immunoprecipitation studies revealed the simultaneous presence of circulating IgG autoantibodies against type VII collagen and laminin alpha 3. A final diagnosis of EBA was based on the sublamina densa level of blister formation. Conclusion: This case illustrates the clinical and immunological overlap between EBA and anti-epiligrin Cicatricial Pemphigoid, a unique finding that may have developed as a consequence of epitope spreading.