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Fenella Wojnarowska - One of the best experts on this subject based on the ideXlab platform.
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Association between the subepidermal autoimmune blistering Diseases Linear IgA Disease and the pemphigoid group and inflammatory bowel Disease: two case reports and literature review
Clinical and experimental dermatology, 2012Co-Authors: Alexa R. Shipman, H. Reddy, Fenella WojnarowskaAbstract:Summary We report two patients with subepidermal autoimmune blistering Diseases and inflammatory bowel Disease (IBD) [one with Linear IgA Disease (LAD) and ulcerative colitis (UC), and the other with mucous membrane pemphigoid (MMP) and Crohn Disease (CD)], and present a review of all previously reported cases. We reviewed the literature, and found 48 cases of patients with autoimmune blistering Diseases and IBD. The blistering Diseases were LAD (25 patients), bullous pemphigoid (BP) (21), MMP (1) and pemphigoid gestationis (1), while the IBD types comprised UC (40) and CD (8). We describe the clinical and immunopathological features and demographic characteristics of the patients. In all but one case, the diagnosis of IBD predated the development of the skin condition. The association was more common with LAD than BP. The immunopathogenesis of IBD and autoimmune blistering Diseases is discussed and a link between them hypothesized, namely, that the presentation of multiple antigens to the immune system during the unregulated inflammation in the bowel wall results in excitation of the immune system and recognition of autologous antigens.
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The localization of the target antigens and antibodies in Linear IgA Disease is heterogeneous, and dependent on the methods used
The British journal of dermatology, 2006Co-Authors: Fenella Wojnarowska, P.m. Collier, J Allen, P.r. MillardAbstract:Fifty-nine patients with Linear IgA Disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS)
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Chronic bullous Disease of childhood and Linear IgA Disease of adults are IgA1-mediated Diseases.
The British journal of dermatology, 2006Co-Authors: Fenella Wojnarowska, Balbir S. Bhogal, Martin M. BlackAbstract:Linear IgA Disease is characterized by the presence of Linear IgA deposits at the basement membrane zone of the skin, and in some cases by circulating basement membrane zone antibodies. The Disease occurs in both adults and children, and is designated adult Linear IgA Disease in the former and chronic bullous Disease of childhood in the latter. The subclass distribution of the circulating and bound basement membrane zone antibodies was studied in 32 children and eight adults. The results were compared with five dermatitis herpetiformis patients and five normal controls. The circulating antibodies (39 patients) and the cutaneous deposits (39 patients) were IgA1 in all 40 patients with Linear IgA Disease. The cutaneous deposits in dermatitis herpetiformis were also all IgA1, and no circulating antibodies were detected. The controls were all negative. This large series of children and adults with Linear IgA Disease demonstrates that the circulating and cutaneous basement membrane zone deposits are all IgA1, and suggests that Linear IgA Disease is an IgA1-mediated Disease.
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Linear IgA Disease of adults: association with lymphoproliferative malignancy and possible role of other triggering factors.
The British journal of dermatology, 2006Co-Authors: Keith M. Godfrey, Fenella Wojnarowska, Jonathan N. LeonardAbstract:Seventy patients with Linear IgA Disease of adults were followed up for a mean of 8.5 years and all malignant Diseases in this group were ascertained. There were three cases of lymphoproliferative malignancy, which constituted a significant excess over the 0.2 cases that would be expected by comparison with an age- and sex-matched population using National Cancer Registry statistics. In contrast, the non-lymphoid malignancy rate of 13% is almost identical to the expected 14%. A subgroup of 35 of the adult Linear IgA Disease patients were assessed with respect to the possible precipitating illnesses or drugs, as well as co-existing medical conditions. Almost one-third of patients described an event that was felt could possibly have triggered the Linear IgA Disease, the most frequent being non-steroidal anti-inflammatory or antibiotic drug therapy, trauma/burns and upper respiratory tract infections. However, it is difficult to determine how often the preceding event is coincidental, and how often, if at all, it is causal.
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Coexistence of psoriasis and Linear IgA Disease in a patient with recent herpes zoster infection.
Clinical and experimental dermatology, 2005Co-Authors: N. Cooke, Fenella Wojnarowska, H. Jenkinson, K. Mckenna, J. AlderdiceAbstract:We report the case of a 29-year-old man with chronic plaque psoriasis who developed Linear IgA Disease following herpes zoster infection. There has only been one previous report describing the coexistence of psoriasis and Linear IgA Disease, which was confirmed by immunopathological studies. In our patient, immunoblotting studies identified IgA antibodies binding to BP180 and BP230 antigens, and IgG autoantibodies binding weakly to the BP180 antigen. This is an interesting case that we believe is an example of epitope spreading in the development of autoimmune subepidermal bullous Diseases.
Detlef Zillikens - One of the best experts on this subject based on the ideXlab platform.
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Linear IgA Disease: Successful Application of Immunoadsorption and Review of the Literature
Dermatology (Basel Switzerland), 2010Co-Authors: Michael Kasperkiewicz, Detlef Zillikens, Markus Meier, Enno SchmidtAbstract:Linear IgA Disease (LAD) is an autoimmune subepidermal blistering disorder characterized by IgA autoantibodies at the dermal-epidermal junction. Conventional first-line treatments include dapsone with or without oral glucocorticosteroids. Various other therapeutic approaches have been used in refractory patients. Immunoadsorption (IA) has been previously successfully applied in severe and/or otherwise treatment-resistant IgG-mediated immunobullous disorders. Here, we report a patient with a severe generalized LAD in whom adjuvant tryptophan IA was associated with rapid healing of skin lesions. Our observation suggests that IA may also be a helpful adjuvant treatment option for severe LAD.
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localized Linear IgA Disease induced by ampicillin sulbactam
Journal of The American Academy of Dermatology, 2004Co-Authors: Iakov Shimanovich, Christian Rose, Cassian Sitaru, E B Brocker, Detlef ZillikensAbstract:Abstract We describe a patient who developed an exclusively perianal-intergluteal vesicular eruption after receiving a course of ampicillin/sulbactam. Direct immunofluorescence microscopy of perilesional skin demonstrated Linear deposits of IgA along the dermal-epidermal junction. Circulating IgA autoantibodies against the 120-kd soluble ectodomain of bullous pemphigoid antigen 180 (LAD-1 autoantigen) were detected by immunoblotting. Discontinuation of the antibiotics resulted in a rapid resolution of the skin lesions. This is a most unusual case of localized drug-induced Linear IgA Disease.
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Localized Linear IgA Disease induced by ampicillin/sulbactam.
Journal of the American Academy of Dermatology, 2004Co-Authors: Iakov Shimanovich, Eva B. Bröcker, Christian Rose, Cassian Sitaru, Detlef ZillikensAbstract:We describe a patient who developed an exclusively perianal-intergluteal vesicular eruption after receiving a course of ampicillin/sulbactam. Direct immunofluorescence microscopy of perilesional skin demonstrated Linear deposits of IgA along the dermal-epidermal junction. Circulating IgA autoantibodies against the 120-kd soluble ectodomain of bullous pemphigoid antigen 180 (LAD-1 autoantigen) were detected by immunoblotting. Discontinuation of the antibiotics resulted in a rapid resolution of the skin lesions. This is a most unusual case of localized drug-induced Linear IgA Disease.
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mapping of epitopes on the bp180 ectodomain targeted by IgA and igg autoantibodies in patients with the lamina lucida type of Linear IgA Disease
Archives of Dermatological Research, 2001Co-Authors: Matthias Georgi, Christian Scheckenbach, Arno Kromminga, Karin Partscht, Gerald Messer, Evabettina Brocker, Detlef ZillikensAbstract:: Linear IgA Disease (LAD) is an autoimmune subepidermal blistering skin Disease characterized by the Linear deposition of IgA at the dermoepidermal junction. Serum from patients with LAD most commonly contains autoantibodies that are directed against the hemidesmosomal transmembrane glycoprotein BP180 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoantibodies in different autoimmune bullous skin Diseases, including bullous pemphigoid and cicatricial pemphigoid (CP). However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we used three recombinant GST fusion proteins, together roughly covering the entire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain. The strongest reactivity was observed with the C-terminal portion of BP180. This is also the major region recognized by autoantibodies in patients with CP. This finding correlates with the observation that there may be significant overlap of the clinical and immunopathological findings in LAD and CP.
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Patients with bullous pemphigoid and Linear IgA Disease show a dual IgA and IgG autoimmune response to BP180.
Journal of autoimmunity, 2000Co-Authors: Arno Kromminga, Matthias Georgi, Christian Scheckenbach, Eva B. Bröcker, Christine Hagel, Rüdiger Arndt, Enno Christophers, Detlef ZillikensAbstract:Bullous pemphigoid (BP) and Linear IgA Disease (LAD) are autoimmune subepidermal blistering skin Diseases associated with autoantibodies against the transmembrane hemidesmosomal protein BP180/type XVII collagen. It has been demonstrated previously that BP is characterized predominantly by IgG autoantibodies, while autoantibodies in LAD mainly belong to the IgA isotype. The aim of the present study was to investIgAte the hypothesis that there is a significant overlap in the autoantibody isotype profiles associated with these two Diseases. Several new recombinant forms of BP180 were generated in the baculovirus expression system, including the full-length protein. IgG autoantibodies to BP 180 were detectable in 39 of 40 (98%) of BP sera; interestingly, 88% of BP sera also contained IgA anti-BP180 autoantibodies. Similarly, anti-BP180 reactivity in LAD sera (n=22) was also attributed to both an IgA (68%) and an IgG (76%) autoantibody response. IgA and IgG autoantibodies to the intracellular portion of BP180 were found in 14% and 28% of BP sera, respectively, and in 8% of LAD sera (same percentage for both isotypes). Our findings clearly demonstrate that both BP and LAD patients have a dual IgA and IgG autoimmune response to BP180 which is directed not only to the ectodomain, but also to the intracellular portion of this protein.
J Allen - One of the best experts on this subject based on the ideXlab platform.
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Dermal-binding Linear IgA Disease: an uncommon subset of a rare immunobullous Disease.
Clinical and experimental dermatology, 2007Co-Authors: A. Lally, J Allen, A. Chamberlain, D. Dean, F. WojnarowskaAbstract:Summary Background. Linear IgA Disease (LAD) is an acquired subepidermal blistering disorder, characterized clinically by urticated plaques, papules, vesicles and bullae. Scarring is not usually observed. Direct immunofluorescence on clinically uninvolved skin shows Linear deposition of IgA at the basement membrane zone (BMZ). Indirect immunofluorescence on salt-split skin shows dermal binding in a minority of cases. Aim. To identify and characterize patients with LAD who have IgA anti-BMZ autoantibodies directed against the dermal side of salt-split human skin (dermal-binding autoantibodies). Methods. This was a retrospective study of patients with a diagnosis of LAD referred to the dermatology department in Oxford between 1986 and 2004, who demonstrated dermal-binding circulating IgA autoantibodies on indirect immunofluorescence. Clinical features were reviewed and target antigens identified by immunoblotting. Results. In total, 17 of 101 patients with LAD were found to have dermal-binding autoantibodies. This subset of LAD was relatively more common in adults than in children. There were no other clinical features that distinguished these patients from others with LAD. Collagen VII, the target antigen in epidermolysis bullosa acquisita (EBA), was identified in two of our cohort, but none of the classic clinical features of mechanobullous EBA was observed. Conclusion. This is the largest cohort of patients with dermal-binding LAD to date. Our patients were clinically indistinguishable from those with non dermal-binding LAD, and showed no evidence of the classic mechanobullous EBA phenotype.
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The localization of the target antigens and antibodies in Linear IgA Disease is heterogeneous, and dependent on the methods used
The British journal of dermatology, 2006Co-Authors: Fenella Wojnarowska, P.m. Collier, J Allen, P.r. MillardAbstract:Fifty-nine patients with Linear IgA Disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients' biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty-nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty-one sera bound to salt-split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt-split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on salt-split skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting.(ABSTRACT TRUNCATED AT 250 WORDS)
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Linear IgA Disease the IgA and igg response to the epidermal antigens demonstrates that intermolecular epitope spreading is associated with IgA rather than igg antibodies and is more common in adults
British Journal of Dermatology, 2003Co-Authors: J Allen, F. WojnarowskaAbstract:Summary Background Linear IgA Disease (LAD; adult and childhood) is a dapsone-responsive, acquired immunobullous disorder mediated by IgA antibodies directed at target antigens within the epithelial basement membrane. These antigens have not been completely characterized. Objectives To identify the target antigens in LAD, and to correlate these with the antibody isotype. Methods We used 101 LAD sera without IgG antibodies detected by indirect immunofluorescence. The sera were analysed by immunoblotting for IgA (65 adults and 36 children) and IgG (61 adults and 34 children) autoantibodies, on salt-split, urea-extracted epidermal tissue extracts. Results Antigens were targeted in LAD by IgA antibodies (54 adults and 23 children), IgG antibodies (34 adults and 19 children), and both isotypes (30 adults and 16 children). Three major antigens were recognized by IgA antibodies: LAD285 (22 adults and three children), BP230 (30 adults and eight children) and BP180 (collagen XVII), including the 97-kDa ectodomain (52 adults and 20 children). Seven ‘minor’ antigens were occasionally detected (18 adults and 13 children). IgA antibodies bound multiple antigens (33 adults and nine children) more frequently than single antigens (21 adults and 14 children), but the binding to multiple antigens was more restricted in children than in adults. IgG antibodies mainly bound a single antigen (29 adults and 16 children), predominantly BP180. Conclusions There was variation in the autoantibody response within the Disease and the patient, with regard to target molecules and autoantibody class. The finding that IgG as well as IgA autoantibodies predominantly target BP180 supports a pivotal role for collagen XVII in adult and childhood LAD. The IgG response was very restricted compared with IgA autoantibodies (P < 0·01). Autoantibodies from children had a more restricted antigen repertoire than from adults (P < 0·05). Epitope spreading is common in LAD and is affected by the class of autoantibody and age of the patient.
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The cellular origins of the Linear IgA Disease target antigens: an indirect immunofluorescence study using cultured human keratinocytes and fibroblasts.
The British journal of dermatology, 2003Co-Authors: J Allen, Tt Phan, Margaret A. Hughes, George W. Cherry, Fenella WojnarowskaAbstract:SummaryBackground Linear IgA Disease (LAD) is an IgA-mediated subepidermal immunobullous Disease of adults and children, with heterogeneous immunopathology. Objectives To investIgAte to what extent the cellular origins of the target antigens account for the heterogeneity of the immune response in LAD. Methods Forty-nine adult and 33 childhood LAD sera were studied. Immunofluorescence was carried out to determine the expression of the LAD antigens by normal human keratinocytes, fibroblasts and mixed cultures of keratinocytes and fibroblasts. Immunoblotting was performed to determine the localization of the LAD target antigens in tissue extracts (48 adult and 31 childhood sera) and cell extracts (21 adult and 10 childhood sera). Results Thirty-one adult and 13 childhood LAD sera bound proteins expressed by human keratinocytes; of these sera, 15 adult and four childhood LAD sera also recognized proteins expressed by fibroblasts. A single adult serum was positive on fibroblasts alone. Seventeen adult and 20 childhood sera were negative on both cell types. There was a modest increase (9%) in the detection of the IgA autoantibodies on keratinocytes and fibroblasts grown together in mixed culture. Immunoblotting showed that the LAD target antigens could be detected in cell as well as in tissue extracts. Conclusions Our results have shown that normal human keratinocytes and fibroblasts in culture express the LAD target antigens. LAD sera (with a single exception) bound antigens expressed by keratinocytes alone or by both keratinocytes and fibroblasts. The principal pattern of expression in keratinocytes was cytoplasmic, similar to that demonstrated by polyclonal antibodies to the 180-kDa bullous pemphigoid antigen (BP180). This reflects the pivotal role of BP180 in LAD. The finding that LAD antigens are expressed by both human keratinocytes and fibroblasts in culture may explain the heterogeneity of the target antigens, and may be a contributory factor in the immunopathology of the Disease.
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Linear IgA Disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein.
The British journal of dermatology, 2003Co-Authors: J Allen, F. WojnarowskaAbstract:Summary Background Linear IgA Disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. Objectives To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. Methods Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). Results Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. Conclusions There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the Disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.
F. Wojnarowska - One of the best experts on this subject based on the ideXlab platform.
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Dermal-binding Linear IgA Disease: an uncommon subset of a rare immunobullous Disease.
Clinical and experimental dermatology, 2007Co-Authors: A. Lally, J Allen, A. Chamberlain, D. Dean, F. WojnarowskaAbstract:Summary Background. Linear IgA Disease (LAD) is an acquired subepidermal blistering disorder, characterized clinically by urticated plaques, papules, vesicles and bullae. Scarring is not usually observed. Direct immunofluorescence on clinically uninvolved skin shows Linear deposition of IgA at the basement membrane zone (BMZ). Indirect immunofluorescence on salt-split skin shows dermal binding in a minority of cases. Aim. To identify and characterize patients with LAD who have IgA anti-BMZ autoantibodies directed against the dermal side of salt-split human skin (dermal-binding autoantibodies). Methods. This was a retrospective study of patients with a diagnosis of LAD referred to the dermatology department in Oxford between 1986 and 2004, who demonstrated dermal-binding circulating IgA autoantibodies on indirect immunofluorescence. Clinical features were reviewed and target antigens identified by immunoblotting. Results. In total, 17 of 101 patients with LAD were found to have dermal-binding autoantibodies. This subset of LAD was relatively more common in adults than in children. There were no other clinical features that distinguished these patients from others with LAD. Collagen VII, the target antigen in epidermolysis bullosa acquisita (EBA), was identified in two of our cohort, but none of the classic clinical features of mechanobullous EBA was observed. Conclusion. This is the largest cohort of patients with dermal-binding LAD to date. Our patients were clinically indistinguishable from those with non dermal-binding LAD, and showed no evidence of the classic mechanobullous EBA phenotype.
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Linear IgA Disease the IgA and igg response to the epidermal antigens demonstrates that intermolecular epitope spreading is associated with IgA rather than igg antibodies and is more common in adults
British Journal of Dermatology, 2003Co-Authors: J Allen, F. WojnarowskaAbstract:Summary Background Linear IgA Disease (LAD; adult and childhood) is a dapsone-responsive, acquired immunobullous disorder mediated by IgA antibodies directed at target antigens within the epithelial basement membrane. These antigens have not been completely characterized. Objectives To identify the target antigens in LAD, and to correlate these with the antibody isotype. Methods We used 101 LAD sera without IgG antibodies detected by indirect immunofluorescence. The sera were analysed by immunoblotting for IgA (65 adults and 36 children) and IgG (61 adults and 34 children) autoantibodies, on salt-split, urea-extracted epidermal tissue extracts. Results Antigens were targeted in LAD by IgA antibodies (54 adults and 23 children), IgG antibodies (34 adults and 19 children), and both isotypes (30 adults and 16 children). Three major antigens were recognized by IgA antibodies: LAD285 (22 adults and three children), BP230 (30 adults and eight children) and BP180 (collagen XVII), including the 97-kDa ectodomain (52 adults and 20 children). Seven ‘minor’ antigens were occasionally detected (18 adults and 13 children). IgA antibodies bound multiple antigens (33 adults and nine children) more frequently than single antigens (21 adults and 14 children), but the binding to multiple antigens was more restricted in children than in adults. IgG antibodies mainly bound a single antigen (29 adults and 16 children), predominantly BP180. Conclusions There was variation in the autoantibody response within the Disease and the patient, with regard to target molecules and autoantibody class. The finding that IgG as well as IgA autoantibodies predominantly target BP180 supports a pivotal role for collagen XVII in adult and childhood LAD. The IgG response was very restricted compared with IgA autoantibodies (P < 0·01). Autoantibodies from children had a more restricted antigen repertoire than from adults (P < 0·05). Epitope spreading is common in LAD and is affected by the class of autoantibody and age of the patient.
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Linear IgA Disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein.
The British journal of dermatology, 2003Co-Authors: J Allen, F. WojnarowskaAbstract:Summary Background Linear IgA Disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. Objectives To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. Methods Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). Results Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. Conclusions There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the Disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.
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Linear IgA Disease: the IgA and IgG response to the epidermal antigens demonstrates that intermolecular epitope spreading is associated with IgA rather than IgG antibodies, and is more common in adults
The British journal of dermatology, 2003Co-Authors: J Allen, F. WojnarowskaAbstract:Summary Background Linear IgA Disease (LAD; adult and childhood) is a dapsone-responsive, acquired immunobullous disorder mediated by IgA antibodies directed at target antigens within the epithelial basement membrane. These antigens have not been completely characterized. Objectives To identify the target antigens in LAD, and to correlate these with the antibody isotype. Methods We used 101 LAD sera without IgG antibodies detected by indirect immunofluorescence. The sera were analysed by immunoblotting for IgA (65 adults and 36 children) and IgG (61 adults and 34 children) autoantibodies, on salt-split, urea-extracted epidermal tissue extracts. Results Antigens were targeted in LAD by IgA antibodies (54 adults and 23 children), IgG antibodies (34 adults and 19 children), and both isotypes (30 adults and 16 children). Three major antigens were recognized by IgA antibodies: LAD285 (22 adults and three children), BP230 (30 adults and eight children) and BP180 (collagen XVII), including the 97-kDa ectodomain (52 adults and 20 children). Seven ‘minor’ antigens were occasionally detected (18 adults and 13 children). IgA antibodies bound multiple antigens (33 adults and nine children) more frequently than single antigens (21 adults and 14 children), but the binding to multiple antigens was more restricted in children than in adults. IgG antibodies mainly bound a single antigen (29 adults and 16 children), predominantly BP180. Conclusions There was variation in the autoantibody response within the Disease and the patient, with regard to target molecules and autoantibody class. The finding that IgG as well as IgA autoantibodies predominantly target BP180 supports a pivotal role for collagen XVII in adult and childhood LAD. The IgG response was very restricted compared with IgA autoantibodies (P
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Vancomycin-induced Linear IgA Disease with autoantibodies to BP180 and LAD285.
The British journal of dermatology, 2001Co-Authors: R A Palmer, J Allen, Graham S. Ogg, A Banerjee, K S Ryatt, R Ratnavel, F. WojnarowskaAbstract:Linear IgA Disease (LAD) is an acquired autoimmune subepidermal bullous Disease characterized by the Linear deposition of IgA at the basement membrane zone. A minority of cases are induced by drugs, of which the most frequently implicated is vancomycin. The target antigens in idiopathic LAD are heterogeneous, but have not previously been reported in vancomycin-induced LAD. We report three cases, and in two of these we investIgAted the target antigens. In both we identified IgA antibodies to LAD285 and IgA and IgG antibodies (dual response) to BP180.
Nuran Alli - One of the best experts on this subject based on the ideXlab platform.
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Chronic Bullous Disease of Childhood in a Patient with Acute Lymphoblastic Leukemia
American Journal of Clinical Dermatology, 2007Co-Authors: Muhterem Polat, Nurdan Lenk, Emin Kürekçi, Pinar Özta, Ferda Artüz, Nuran AlliAbstract:Linear IgA Disease is characterized by the presence of Linear IgA deposits in the basement membrane zone of the skin, and circulating basement membrane zone antibodies are detected in 80% of cases. The Disease occurs in both adults and children, and is designated adult Linear IgA Disease in the former and chronic bullous Disease of childhood (CBDC) in the latter. We describe a 5-year-old boy with acute lymphoblastic leukemia in remission, in whom CBDC developed after treatment with trimethoprim/sulfamethoxazole (cotrimoxazole). To our knowledge, this is the first reported case of possible drug-induced CBDC.
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Chronic bullous Disease of childhood in a patient with acute lymphoblastic leukemia: possible induction by a drug.
American journal of clinical dermatology, 2007Co-Authors: Muhterem Polat, Nurdan Lenk, Emin Kürekçi, Ferda Artüz, Pınar Öztaş, Nuran AlliAbstract:Linear IgA Disease is characterized by the presence of Linear IgA deposits in the basement membrane zone of the skin, and circulating basement membrane zone antibodies are detected in 80% of cases. The Disease occurs in both adults and children, and is designated adult Linear IgA Disease in the former and chronic bullous Disease of childhood (CBDC) in the latter. We describe a 5-year-old boy with acute lymphoblastic leukemia in remission, in whom CBDC developed after treatment with trimethoprim/sulfamethoxazole (cotrimoxazole). To our knowledge, this is the first reported case of possible drug-induced CBDC.