Intercellular IgA dermatosis Tsuruta, D.
British journal of dermatology (1951),
January 2017, 2017-Jan, 2017-01-00, 20170101, Volume:
176, Issue:
1
Journal Article
Peer reviewed
Linked Article: Hashimoto et al. Br J Dermatol 2017; 176:168–175.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Although there are many reports of sporadic patients with paraneoplastic pemphigus (PNP), only a few systematic studies on large cohorts of patients with PNP have been reported.
...Objectives
To analyse the clinical and immunological findings in a large cohort of patients with PNP.
Methods
This retrospective study consisted of 104 patients with PNP. Clinical and histopathological manifestations, associated neoplasms, complicating diseases, prognosis and results of immunofluorescence, immunoblotting and enzyme‐linked immunosorbent assays (ELISAs) were analysed.
Results
The clinical and histopathological findings in this study were generally similar to those in previous reports. The most common associated neoplasms included malignant lymphomas, malignant solid tumours and Castleman disease, in that order, while 12 patients had no detectable tumours. Novel ELISAs for desmocollins (Dscs) showed that 19 (18·6%), 42 (41·2%) and 62 (60·8%) of 102 patients with PNP showed antibodies to Dsc1, Dsc2 and Dsc3, respectively. Thirty‐two (60%) of 53 patients had antibodies to alpha‐2‐macroglobulin‐like protein 1 (A2ML1). We found statistically significant correlations between positive desmoglein 3 reactivity and genital lesions, and between positive desmoglein 3 reactivity and bronchiolitis obliterans.
Conclusions
We consider that antibodies to Dscs and A2ML1 are useful for the diagnosis of PNP.
What's already known about this topic?
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease with polymorphous mucocutaneous lesions associated with either benign or malignant neoplasms.
Bronchiolitis obliterans with progressive respiratory failure is a cause of death in PNP.
What does this study add?
Several patients with PNP with typical clinical and immunological features did not show detectable neoplasms.
Antidesmocollin autoantibodies and antialpha‐2‐macroglobulin‐like protein 1 antibodies are useful for the diagnosis of PNP.
Linked Comment: Sprecher, Br J Dermatol 2015; 173: 1363–64.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Although many new disease entities of autoimmune bullous disease (AIBD) have recently been recognized, satisfactory immunological diagnostic methods and comprehensive ...classifications for various AIBDs have not been established.
Objectives
To identify immunological diagnostics and comprehensive classifications for AIBDs.
Methods
We selected and examined 4774 patients with various AIBDs from our cohort of 5063 patients with difficult AIBDs, whose sera and information were sent for our diagnostic method from other institutes in either Japan or other countries over the last 19 years. We examined the sera by our immunological diagnostic methods including various immunofluorescence, immunoblotting and enzyme‐linked immunosorbent assay tests to make final diagnoses.
Results
By our immunological diagnostic methods, we successfully made final diagnoses for approximately three‐quarters of the difficult cases of AIBD, although the remaining cases could not be diagnosed. Using the results, we suggest the most extensive and newest classification of AIBDs, and also propose the most efficient algorithm of immunological tests for the diagnosis of various AIBDs.
Conclusions
The results in this study of 4774 patients with various AIBDs indicate that our immunological diagnostic method is useful for making diagnoses for most patients with AIBD. However, we need further improvements including new immunological techniques to establish more satisfactory methods.
What's already known about this topic?
There are many different autoimmune bullous diseases (AIBDs) that are diagnosed by immunological tests, in addition to clinical and histopathological examinations.
As one of the centres for diagnosis of AIBDs in Japan, we have collected sera and information for more than 5000 difficult cases of various AIBDs over the last 19 years, and have performed various serological tests.
What does this study add?
This study presents the current classification and algorithm for immunological diagnosis in AIBDs.
This study also presents the final diagnoses for our 4774 patients with AIBDs, which were made by our immunological diagnostic method.
What is the translational message?
This study proposes a comprehensive novel classification of AIBDs, which should be useful for precise and detailed diagnoses of various AIBDs in the clinical field.
The large number of immunological and molecular methods described in this study should also facilitate clinical practice, such as for diagnoses and appropriate selection of treatments, for various AIBDs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
IgE autoantibodies are considered to be involved in the pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes.
Objectives
To develop ...reliable enzyme‐linked immunosorbent assays (ELISAs) for the detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features.
Methods
We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amounts of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of the IgE ELISAs were statistically compared with various ELISAs and various clinical parameters, including our own severity scores and BP phenotypes.
Results
IgG adsorption generally showed no changes in sensitivity and specificity for IgE ELISAs, although slight cross‐reactivity of anti‐IgE secondary antibody to IgG and interference of excess amounts of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 were found in 21 of 36 BP sera and IgE autoantibodies to BP230 were found in 18 of 36 BP sera. The results of IgG and IgE ELISAs for both BP180 and BP230 were well correlated. IgG and IgE anti‐BP180 antibodies correlated with disease activity but IgG and IgE anti‐BP230 autoantibodies did not. IgE anti‐BP230 autoantibodies correlated with nodular phenotype but not erythematous phenotype.
Conclusions
The results of this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti‐BP180 autoantibodies seemed to be pathogenic, while an association between IgE autoantibodies and inflammatory BP phenotype was not indicated.
What's already known about this topic?
Although recent studies have indicated that IgE autoantibodies are frequently detected in bullous pemphigoid (BP), in addition to IgG autoantibodies, their diagnostic and pathogenic relevance have not been fully documented.
Reliable IgE enzyme‐linked immunosorbent assays (ELISAs) for BP antigens, particularly BP230, have not been established.
What does this study add?
This study establishes reliable diagnostic IgE ELISAs for both BP180 and BP230, in which the influence of excess amounts of IgG autoantibodies was extensively determined.
This study confirms the frequent detection of IgE autoantibodies to BP180 and BP230. IgE autoantibodies to BP180 correlated with disease activity, and IgE anti‐BP230 antibodies correlated with nodular phenotypes, while they were not correlated with the inflammatory erythematous phenotype.
What is the translational message?
We have developed reliable IgE ELISAs for both BP180 and BP230, which can be used in clinical practice.
This study suggests that titres of IgE anti‐BP180 autoantibodies correlated with disease activity in BP and should be clinically useful for selecting the best treatment, particularly with regard to anti‐IgE antibody therapy.
Linked Comment: Hammers and Payne. Br J Dermatol 2017; 177:13–14
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
6.
Female pattern hair loss with acromegaly Mizukami, Y.; Sugawara, K.; Tsuruta, D.
Clinical and experimental dermatology,
April 2021, 2021-Apr, 2021-04-00, 20210401, Volume:
46, Issue:
3
Journal Article
Peer reviewed
Click here for the corresponding questions to this CME article.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin ...(Dsc) is at present unknown. No consistent immunoassay for immunoglobulin (Ig) G autoantibodies to Dscs has been developed.
Objectives
The aim of this study was to develop reliable assays to detect anti‐Dsc autoantibodies.
Methods
We expressed soluble recombinant proteins (RPs) of human Dsc1–3 in mammalian cells and examined sera of various types of pemphigus, including 79 paraneoplastic pemphigus (PNP) sera, by novel enzyme‐linked immunosorbent assays (ELISAs) using the RPs. We also performed ELISAs of Dsc baculoproteins and used the complementary DNA (cDNA) transfection method, and compared the results with those of mammalian ELISAs.
Results
Through mammalian ELISAs, IgG autoantibodies to Dsc1, Dsc2 and Dsc3 were detected in 16·5%, 36·7% and 59·5% of PNP sera, respectively, and considerable numbers of pemphigus herpetiformis (PH) and pemphigus vegetans (PVeg) sera reacted strongly with Dsc1 and Dsc3. Mammalian ELISAs were highly specific and more sensitive than baculoprotein ELISAs or the cDNA transfection method. Several Dsc‐positive sera, particularly PH sera, showed no reactivity with Dsgs. The reactivity of PNP serum and PVeg serum with Dscs was not abolished by pre‐absorption with Dsg RPs.
Conclusions
The results of these novel ELISAs indicated that IgG anti‐Dsc autoantibodies were frequently detected and potentially pathogenic in nonclassical pemphigus.
What's already known about this topic?
Despite the established pathogenic role of anti‐desmoglein (Dsg) antibodies in classical pemphigus, the significance of autoantibodies to another desmosomal cadherin, desmocollin (Dsc), is at present unknown.
No consistent immunoassay for IgG autoantibodies to Dscs has been developed.
What does this study add?
We have successfully established new sensitive and specific mammalian Dsc immunoglobulin (Ig) G enzyme‐linked immunosorbent assays.
Our data show that IgG anti‐Dsc autoantibodies are frequently detected and potentially pathogenic in particular types of nonclassical pemphigus.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Background
Epidermolysis bullosa acquisita (EBA) is a rare pemphigoid disease involving autoantibodies to type VII collagen (COL7), a major structural component of anchoring fibrils. IgE ...autoantibodies to type XVII collagen (BP180) have been identified in bullous pemphigoid (BP), the prototype of pemphigoid diseases. Although the pathogenic relevance of IgG anti‐COL7 has been investigated, that of IgE in EBA remains unclear.
Objectives
To reveal the presence and pathogenic relevance of IgE anti‐COL7 in EBA.
Methods
We examined IgE antibodies in 109 patients with EBA by indirect immunofluorescence (IIF) and enzyme‐linked immunosorbent assay (ELISA).
Results
IIF with normal human skin revealed IgE reactivity in the basement membrane zone in 29 (26·6%) cases. To verify whether the IgE antibodies were specific to COL7, we performed IIF with 21 clearly positive cases and the skin of a patient with dystrophic EBA, which does not involve COL7. All cases showed negative results, indicating that IgE antibodies were specific to COL7. In a modified IgG COL7 ELISA for IgE, 16 (14·7%) cases were positive (three and 13 cases were negative and positive on IIF, respectively). We compared anti‐COL7 IgG and IgE, and found a weak but significant correlation (r = 0·459, P < 0·001). EBA is clinically divided into a mechanobullous (MB; noninflammatory) type and an inflammatory (INF) type resembling BP. Of the IIF‐positive cases, 11 of 30 (37%) had INF and nine of 48 (19%) had MB.
Conclusions
This study is the first to demonstrate the presence of circulating anti‐COL7 IgE in patients with EBA, which may correlate with the clinical phenotype.
What's already known about this topic?
Epidermolysis bullosa acquisita (EBA) is a rare pemphigoid disease in which autoantibodies, mainly IgG, target type VII collagen.
In bullous pemphigoid, the prototype of pemphigoid diseases, IgE autoantibodies to type XVII collagen (BP180) have been detected and are reported to be associated with disease severity.
However, no study has yet investigated the presence of IgE autoantibodies to type VII collagen in EBA.
What does this study add?
IgE anti‐type VII collagen antibodies were also detected in sera from patients with EBA, with concomitant elevated total IgE.
IgE anti‐basement membrane zone‐positive cases appear to occur more frequently in inflammatory‐type EBA than in noninflammatory‐type EBA.
IgE anti‐type VII collagen may correlate with the clinical phenotype in EBA.
What is the translational message?
IgE and type VII collagen‐specific IgE could be a therapeutic target for EBA.
Linked Comment: Ludwig. Br J Dermatol 2019; 180:981–983.
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