Published papers

Background: The thymus plays an essential role in removing autoreactive T cells. Autoantigen-expressing thymic epithelial cells (TECs) contribute to the tolerogenic process. The thymus transiently shrinks as an acute thymic involution (ATI) under various inflammatory conditions. However, whether ATI occurs during local skin inflammation remains unclear, as does its influence on thymic immune tolerance. Objective: We investigated whether imiquimod-induced dermatitis causes ATI and impairs thymic immune tolerance against desmoglein 3 (Dsg3), an epidermal autoantigen of pemphigus vulgaris. Methods: 5% imiquimod cream was applied daily, at 62.5 mg/day (high dose group) or 31.25 mg/day (low dose group), for 1 week on the back of wild-type mice, and to wild-type mice that had undergone bone-marrow transplantation from Dsg3-specific T-cell receptor (TCR) transgenic-Rag2−/− mice. Next, thymocytes, TECs and other immune cells were analyzed by flow cytometry. TEC-associated Dsg3 expression was also analyzed by immunofluorescence staining. Results: Thymus weight and thymocyte number in all developmental stages decreased in a dose-dependent manner under imiquimod-induced dermatitis. The number of total TECs, specifically medullary, but not cortical, TECs, decreased in high and low dose groups. Accordingly, the number of Dsg3-experssing UEA-1+keratin 5+mTEC decreased in the thymus during imiquimod-induced dermatitis. Although Dsg3-sepcific transgenic thymocytes was usually deleted in the thymus under physiological condition by central tolerance, Dsg3-sepcific transgenic CD4+CD8− thymocytes significantly increased in number under imiquimod-induced dermatitis. Conclusion: These findings indicate a crosstalk between skin and thymus in adult mice and suggest that skin inflammation may impair thymic tolerance to autoantigens, such as Dsg3.

Intravenous Ig (IVIG) is a treatment option for intractable cases of pemphigus vulgaris (PV), an autoimmune blistering disease caused by autoantibodies against desmoglein 3 (DSG3). To investigate the efficacy of IVIG on autoantibody secretion, we produced PV model mice by adoptive transfer of immunized Dsg3−/− splenocytes to Rag2−/− mice. We found that circulating anti-DSG3 IgG ELISA titer decreased in PV model mice after 5 days of treatment with IVIG compared with PBS-treated mice, whereas the F(ab’)2 fragment did not suppress the anti-DSG3 IgG titer. enzyme-linked immunospot assay revealed that IVIG treatment reduced the frequency of anti-DSG3 antibody–secreting cells in the spleen but not in lymph nodes and bone marrow. Moreover, this reduction was observed only in the splenic B220− fraction but not in the B220+ fraction. Furthermore, IVIG decreased the serum levels of anti-DSG3 IgG, even after a significant reduction of its titer, owing to antibody-mediated CD20+ B cell depletion. In addition, IVIG suppressed anti-DSG3 IgG production in B220−CD138+ plasma cells derived from PV model mice ex vivo. These results indicate that IVIG reduced autoantibody production in B220− cells containing plasma cells in PV model mice, and this function may indicate one of the mechanisms of action of IVIG on PV.

Background: Recognition of rocuronium-induced anaphylaxis is often challenging, owing to its diverse clinical manifestations. Regarding treatment, several reports have described the efficacy of sugammadex, while conflicting reports have also been published. Case: A 71-year-old man was scheduled to undergo split-thickness skin grafting surgery on his hip. During the induction of general anesthesia, the patient developed profound circulatory collapse without any cutaneous manifestations, which required 40 min of cardiopulmonary resuscitation. Later, the patient developed circulatory collapse again during the induction of anesthesia for tracheostomy surgery, which apparently coincided with the administration of rocuronium. Rocuronium-induced anaphylactic shock was suspected, and the administration of sugammadex resulted in swift recovery of hemodynamics. The basophil activation test revealed a positive reaction to rocuronium. Conclusion: The possibility of rocuronium-induced anaphylaxis should be considered when the circulatory collapse coincides with rocuronium administration, even though cutaneous manifestation is absent. Sugammadex can be a treatment option in such atypical cases.

MicroRNAs are important regulators of immune responses. Here, we show miR-221 and miR-222 modulate the intestinal Th17 cell response. Expression of miR-221 and miR-222 was induced by proinflammatory cytokines and repressed by the cytokine TGF-β. Molecular targets of miR-221 and miR-222 included Maf and Il23r, and loss of miR-221 and miR-222 expression shifted the transcriptomic spectrum of intestinal Th17 cells to a proinflammatory signature. Although the loss of miR-221 and miR-222 was tolerated for maintaining intestinal Th17 cell homeostasis in healthy mice, Th17 cells lacking miR-221 and miR-222 expanded more efficiently in response to IL-23. Both global and T cell-specific deletion of miR-221 and miR-222 rendered mice prone to mucosal barrier damage. Collectively, these findings demonstrate that miR-221 and miR-222 are an integral part of intestinal Th17 cell response that are induced after IL-23 stimulation to constrain the magnitude of proinflammatory response.

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/ TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005–2007 and between 2008–2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. Cytotoxic T cells and associated effector molecules are known to drive SJS/TEN pathophysiology, but the contribution of innate immune responses is not well understood. We describe a mechanism by which neutrophils triggered inflammation during early phases of SJS/TEN. Skin-infiltrating CD8+ T cells produced lipocalin-2 in a drug-specific manner, which triggered the formation of neutrophil extracellular traps (NETs) in early lesional skin. Neutrophils undergoing NETosis released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1 expression caused keratinocytes to be vulnerable to necroptosis that caused further release of LL-37 by necroptotic keratinocytes and induced FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. The NETs-necroptosis axis was not observed in less severe cutaneous adverse drug reactions, autoimmune diseases, or neutrophil-associated disorders, suggesting that this was a process specific to SJS/TEN. Initiation and progression of SJS/TEN keratinocyte necroptosis appear to involve a cascade of events mediated by innate and adaptive immune responses, and understanding these responses may contribute to the identification of diagnostic markers or therapeutic targets for these adverse drug reactions.

Antigen-specific peripheral tolerance is crucial to prevent the development of organ-specific autoimmunity. However, its function decoupled from thymic tolerance remains unclear. We used desmoglein 3 (Dsg3), a pemphigus antigen expressed in keratinocytes, to analyze peripheral tolerance under physiological antigen-expression conditions. Dsg3-deficient thymi were transplanted into athymic mice to create a unique condition in which Dsg3 was expressed only in peripheral tissue but not in the thymus. When bone marrow transfer was conducted from high-avidity Dsg3-specific T cell receptor–transgenic mice to thymus-transplanted mice, Dsg3-specific CD4+ T cells developed in the transplanted thymus but subsequently disappeared in the periphery. Additionally, when Dsg3-specific T cells developed in Dsg32/2 mice were adoptively transferred into Dsg3-sufficient recipients, the T cells disappeared in an antigen-specific manner without inducing autoimmune dermatitis. However, Dsg3-specific T cells overcame this disappearance and thus induced autoimmune dermatitis in Treg-ablated recipients but not in Foxp3-mutant recipients with dysfunctional Tregs. The molecules involved in disappearance were sought by screening the transcriptomes of wild-type and Foxp3-mutant Tregs. OX40 of Tregs was suggested to be responsible. Consistently, when OX40 expression of Tregs was constrained, Dsg3-specific T cells did not disappear. Furthermore, Tregs obtained OX40L from dendritic cells in an OX40-dependent manner in vitro and then suppressed OX40L expression in dendritic cells and Birc5 expression in Dsg3-specific T cells in vivo. Lastly, CRISPR/Cas9-mediated knockout of OX40 signaling in Dsg3-specific T cells restored their disappearance in Treg-ablated recipients. Thus, Treg-mediated peripheral deletion of autoreactive T cells operates as an OX40-dependent regulatory mechanism to avoid undesired autoimmunity besides thymic tolerance.

The identification of risk factors is key not only to uncover the pathogenesis of autoimmune disease but also to predict progression to autoimmune disease. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms is likely the best prototypic example for analyzing the sequential events. We conducted a retrospective study of 55 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms followed up for the possibility of later development of autoimmune disease ∼18 years after resolution. Nine patients progressed to autoimmune sequelae regardless of treatment. The generation of autoantibodies was preceded by 8 years in eight of the nine patients. The combination of increases in lymphocyte counts, severe liver damage, a rebound increase in globulin, persistent reactivations of Epstein‒Barr virus and human herpesvirus-6, and low IL-2 and IL-4 at the acute/subacute phases were significant risk factors for the future development of autoimmune disease. On the basis of these factors, we established a scoring system that can identify high-risk patients. When stratified these patients into three risk categories (low/intermediate/high), occurrence of autoimmune disease was exclusively detected in the high group. Our data represent a scoring system to identify patients at high risk of developing autoimmune disease, although a larger study is required to validate the scoring system.

Background: Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce. Methods: We conducted a matched case–control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score. Results: From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of “probable” or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated “unlikely” in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were “very unlikely”. Conclusions: This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

Food allergy is a typical immediate-onset allergic disease in which symptoms are provoked by exposure to the sensitized antigens. Although previous reports have shown that omalizumab has helped children with egg or milk allergy achieve oral immunotherapy safely, there is still no established method for induction of remission in adult food allergy. A 51-year-old woman with oral steroid-dependent severe asthma was treated with omalizumab for 6 years. She had shellfish and wheat food allergy and oral allergy syndrome induced by kiwi and other foods associated with latex-fruit syndrome. Since omalizumab treatment, her food allergy symptoms had disappeared. After 7 years of this treatment, disseminated erythema suddenly appeared; omalizumab was discontinued because of suspected drug-induced eruption. After omalizumab interruption, she felt an itching sensation in her throat with worsened asthma control immediately after wheat ingestion. Readministration of omalizumab improved these symptoms. Thus, we raised the possibility that omalizumab not only improved asthma control but also induced pharmacological remission of the patient's food allergy. Omalizumab may be considered as a treatment option for adult patients with food allergies and severe asthma.

Background: Pemphigus vulgaris (PV) is an autoimmune bullous disease mediated by autoantibodies against desmoglein 3 (DSG3). Inducible costimulator (ICOS) is a costimulatory receptor expressed on T cells and influences the activity of T follicular helper (TFH) cells in various autoimmune diseases, but the roles of ICOS and TFH cells in PV remain unclear. Objective: We examined the immunological characteristics, antigen specificity, and pathogenicity of CD4+ T-cell subpopulations, as well as the therapeutic effect of anti-ICOS blocking antibodies in PV. Methods: A mouse model of PV was established by adoptive transfer of immune cells from the skin-draining lymph nodes or spleens of DSG3-expressing skin-grafted Dsg3–/– mice into Rag1–/– mice. The TFH cells and CD4+ T cells in PBMCs from PV patients were examined by flow cytometry. Results: Among CD4+ T cells from the mouse model, ICOS-positive TFH cells were associated with B-cell differentiation and were required for disease induction. Using an MHC class II tetramer, DSG3-specific ICOS+ TFH cells were found to be associated with anti-DSG3 antibody production and expanded in the absence of B cells. In human PV, the frequency of ICOS+CXCR5+PD-1+ memory CD4+ T cells correlated with the autoantibody level. Treatment with anti-ICOS blocking antibodies targeting ICOS+ TFH cells decreased the anti-DSG3 antibody level and delayed disease progression in vivo. Conclusions: Mouse Dsg3-specific ICOS+ TFH cells and human ICOS+CXCR5+PD-1+ TH cells are associated with the anti-DSG3 antibody response in PV. ICOS expressed on CXCR5+PD-1+ TH cells may be a therapeutic target for PV.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening severe cutaneous adverse reactions (SCARs). The first national epidemiological survey of SJS/TEN was carried out in 2008. We conducted a new survey to identify changes from the previous survey. Objective: The present survey aimed to estimate the number of SJS/TEN patients in Japan between 2016 and 2018 (primary survey) and to clarify clinical epidemiological profiles (secondary survey). Methods: A primary survey asking for numbers of SJS/TEN patients during the study period was sent to 1205 institutions nationwide. A secondary survey was sent to institutions reporting SJS/TEN patients, seeking detailed information. Results: Yearly prevalence per million was 2.5 for SJS and 1 for TEN. The secondary survey allowed analysis of 315 SJS cases and 174 TEN cases from 160 institutions. Mean age was 53.9 years in SJS, and 61.8 years in TEN. Mortality rate was 4.1 % for SJS and 29.9 % for TEN. In TEN, mean age and mortality rates had increased from the previous survey. The ratio of expected to observed mortality calculated by SCORTEN score was lowest with high-dose steroid therapy (0.40), followed by steroid pulse therapy (0.52). Conclusion: The present findings suggest that the mortality rate of TEN has increased because of increases in mean ages of patients and patients with malignant neoplasm as underlying disease. When comparing the ratio of expected mortality to actual mortality, high-dose steroid therapy achieved the greatest reduction in mortality.

Autoimmune bullous diseases (AIBDs) are skin disorders which are mainly induced by autoantibodies against desmosomal or hemidesmosomal structural proteins. Previous studies using patients’ samples and animal disease models identified target antigens and elucidated the mechanisms of blister formation. Pemphigus has been the subject of more active clinical and basic research than any other AIBD. These efforts have revealed the pathogenesis of pemphigus, which in turn has led to optimal diagnostic methods and novel therapies, such as rituximab. In bullous pemphigoid (BP), studies with passive-transfer mouse models using rabbit anti-mouse BP180 antibodies and studies with passive-transfer or active mouse models using autoantigen-humanized mice elucidated the immune reactions to BP180 in vivo. Recently, dipeptidyl peptidase-4 inhibitors have attracted attention as a trigger for BP. For epidermolysis bullosa acquisita (EBA), investigations using mouse models are actively under way and several molecules have been identified as targets for novel therapies. In this review, we give an overview and discussion of the recent progress in our understanding of the pathogenesis of pemphigus, BP, and EBA. Further studies on the breakdown of self-tolerance and on the identification of key molecules that are relevant to blister formation may expand our understanding of the etiology of AIBDs and lead to the development of novel therapeutic strategies.

© 2017 Japanese Dermatological Association Azathioprine (AZP) is used as a corticosteroid (CS)-sparing medication to treat autoimmune blistering diseases. In this study, we examined the efficacy of AZP and the feasibility of using AZP monotherapy (without CS) to treat pemphigus and pemphigoid. We performed a retrospective study of 10 Japanese patients (seven with pemphigus and three with pemphigoid) with mild to moderate disease activity who had been treated using AZP. The treatment efficacy was evaluated based on decreases in the disease activity scores and autoantibody titers. The results demonstrate that seven out of 10 cases (70%) were treated successfully using AZP monotherapy with no severe adverse effects. The disease activity scores of the successfully-treated patients decreased to zero after 1–37.5 months (average, 11.9) and the average disease activity scores in these cases decreased significantly at 2 months (38.2 ± 36.6%) compared with the scores of the three patients who required additional systemic CS therapy (77.5 ± 3.5%) (P < 0.05). Additionally, the autoantibody titers of five cases treated successfully using AZP decreased by half at 6 months. In conclusion, our findings suggest that AZP monotherapy is a viable treatment option for mild to moderate pemphigus and pemphigoid.

© The Japanese Society for Immunology. 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Autoimmune diseases are devastating conditions in which the immune system is directed against the host, leading to life-threatening destruction of organs. Although autoantigens are ill-defined in most autoimmune diseases, this is not the case in the skin. Autoimmune bullous diseases have been extensively studied with detailed characterization of autoantigens, the epitopes that are targeted, and the mechanisms of action that mediate autoimmune tissue destruction. Pemphigus is an autoimmune bullous disease caused by circulating IgG that targets two desmosomal proteins, desmoglein 1 and 3, which are crucial for cell-cell adhesion of keratinocytes. Binding of auto-antibodies to desmogleins impairs keratinocyte adhesion, leading to severe blistering disease. Mouse models that recapitulate the human disease have been instrumental in elucidating the detailed pathophysiology. Taking advantage of the fact that desmogleins are specifically targeted in pemphigus, studying humoral and cellular autoimmunity against these autoantigens provides us with an opportunity to understand not only the effector mechanisms of B and T cells in mediating pathology but also how autoreactive lymphocytes are regulated during development in the thymus and post-development in the periphery. This review introduces pemphigus and its subtypes as prototypic autoimmune diseases from which recent basic and translational developments should provide insight into how autoimmunity develops.

© 2019 British Association of Dermatologists Background: A subset of patients with bullous pemphigoid (BP) show deposition of IgE in the basement membrane zone (BMZ), yet the relationship between BMZ IgE and the clinical presentation of BP remains unclear. Objectives: To investigate the relationship between IgE deposition, IgE levels in serum, and disease severity in patients with BP. Methods: We investigated IgE autoantibodies in 53 patients with BP by direct immunofluorescence (DIF), indirect immunofluorescence and enzyme-linked immunosorbent assay. Results: Of 53 patients with BP, 23 (43%) had IgE deposition, 10 (19%) of whom were IgE+ and 13 (25%) IgE± according to DIF analyses. Erosion/blister (E/B) Bullous Pemphigoid Disease Area Index (BPDAI) scores were significantly higher in IgE+ patients than in IgE− patients (n = 15), while no significant differences were found for urticaria/erythema BPDAI scores. IgE+ and IgE± patients took longer to reduce their E/B BPDAI score by 75% after systemic corticosteroid treatment. BP180-IgE levels were significantly higher among IgE+ patients than IgE± or IgE− patients (n = 10). Total IgE levels in the serum and blood eosinophil counts did not differ between IgE+, IgE± and IgE− patients. A significant correlation was detected between BP180-IgG and BP180-IgE, but not between BPDAI scores and any of BP180-IgG, BP180-IgE or blood eosinophil count. Conclusions: IgE deposition in the BMZ is associated with higher E/B BPDAI scores and longer treatment periods. We conclude that IgE binding in the BMZ may contribute to BP pathogenesis by promoting blister formation. What's already known about this topic?. BP180-IgE autoantibodies have an important role in the pathogenesis of bullous pemphigoid (BP). A subset of patients with BP display deposition of IgE within the basement membrane zone (BMZ) of skin tissue. What does this study add?. Patients with in vivo IgE deposition in the BMZ displayed higher erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) scores, while urticaria/erythema BPDAI scores were not significantly different. Patients with in vivo IgE deposition in the BMZ took longer to reduce their erosion/blister BPDAI score by 75% after systemic corticosteroid treatment. BP180-specific IgE levels in serum were higher among patients with linear IgE deposition in the BMZ than in those with granular or no IgE deposition.

The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene (Adam10)flox/flox/Lyz2-Cre (Adam10DLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10DLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-a, IL-1b, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10DLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocyte/macrophage-like phenotype, were significantly increased in the lungs of Adam10DLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10DLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10DLyz2 mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10DLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.

Background: The detection of serum anti-desmoglein (Dsg) IgG autoantibodies has been reported to be useful for assessment of disease activity in pemphigus. However, previous studies have reported that anti-Dsg autoantibodies remain detectable in some patients without active pemphigus lesions. Objectives: To investigate the clinical characteristics and antibody pathogenicity of pemphigus patients positive for anti-Dsg IgG autoantibodies in remission. Methods: We retrospectively investigated pemphigus patients with a history of clinical remission who visited the Department of Dermatology of Keio University during 2019 and 2020. The antibody pathogenicity was assessed by bead aggregation assay. Results: When patients were recognized as having entered remission (PDAI = 0 and PSL ≦ 10 mg/day for 2 months), serum autoantibodies against Dsg were detected in 72 of 132 patients (54.5%, positive group; PG), but were not detected in 60 patients (45.5%, negative group; NG). Anti-Dsg antibody titres in remission declined from the active phase in 33 patients in the PG for whom data were available. There were no differences in the chance of reducing PSL to 5 mg/day (P = 0.885) and rate of relapse (P = 0.279) between PG and NG, but fewer patients in PG discontinued corticosteroids (P = 0.004). The ability of patients' sera to block aggregation of Dsg/desmocollin beads was significantly reduced in remission compared to the active phase. However, our results revealed that whole sera in remission still had pathogenic activity in seven of nine patients, and the approximately equal amounts of anti-Dsg antibodies in active phase and remission showed similar pathogenicity. Conclusions: This study will provide guidance in cases where autoantibodies are found to be positive in pemphigus patients during remission or steroid reduction.