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Background: Dermatomyositis (DM) is an idiopathic immune-mediated myopathy, and may involve many organs, including muscles, skin and lungs. Myositis-specific autoantibodies (MSAs) are a useful aid in diagnosis DM and identifying its clinical subtype. During the COVID-19 pandemic, several studies found clinical similarities regarding lung involvement in both COVID-19 and DM. Such similarities have prompted speculation of a common pathogenetic mechanism. Indeed, viral infections are well-known triggers of autoimmune diseases. This prompted us to investigate whether circulating MSAs could be markers of the severity of lung involvement and of clinical outcome in COVID-19 patients. Moreover, we investigated the presence of cutaneous signs of DM in COVID-19 patients., Methods: We conducted a retrospective cohort study on 178 hospitalized patients affected by COVID-19. The diagnosis was confirmed by naso-pharyngeal swab positivity for SARS-CoV-2. The severity of lung involvement was assessed by assigning to each patient a radiological score ranging from 1 to 4, based on chest imaging (chest X-rays or CT scans). Serum samples were tested for MSAs., Results: Anti-PL-7 antibodies were detected in 10.1% of patients and were found to be associated with an increased risk of severe pulmonary involvement ( p = 0.019) and a worse prognosis in COVID-19 patients. Cutaneous lesions were observed in 26.4% of patients. However, none were cutaneous manifestations of DM., Conclusions: The detection of anti-PL7 antibodies might predict severe pulmonary involvement and a worse prognosis in COVID-19 patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Linear IgA bullous dermatosis (LABD) is characterized by presence of multiple IgA autoantibodies, and a comparatively lesser number of IgG antibodies, directed against different hemidesmosomal antigens. The main autoantigens are LAD-1, LABD-97, BP180 and BP230, type VII collagen and laminin 332. We retrospectively studied the serology of 54 Italian patients with LABD using enzyme-linked immunosorbent assay (ELISA), immunoblotting assay, and indirect immunofluorescence on monkey oesophagus and salt-split skin. Among these, indirect immunofluorescence of salt-split skin elicits the greatest sensitivity. Sixty-three percent of the sera were observed to be positive, with a lamina lucida pattern observed in 48%, a sub-lamina densa pattern in 2% and a mixed pattern in 13% of the cases. IgA reactivity to LAD-1 on immunoblotting was found in 52% of sera, to BP180-NC16A by ELISA in 32% and to BP230 in 26%. Only 17% of patients possessed circulating IgG autoantibodies. LAD-1 was determined to be a major autoantigen of the lamina lucida subtype. Combined serological assays demonstrated a high sensitivity (82%), suggesting that this approach could support diagnosis when a biopsy is not feasible or direct immunofluorescence results are negative.

Objective: Our objective was to characterize the demographic information, clinical features, and laboratory data of patients with dermatitis herpetiformis (DH)., Methods: In this multicentre cross-sectional study, consecutive patients with a new diagnosis of DH that referred to nine different Italian centers between 2011 and 2016 were characterized assessing demographic, clinical and laboratory findings, and evaluating gender and age differences across selected variables., Results: A total of 151 patients were included. Among them, 81 (53.6%) were males and 70 (46.4%) were females, with a male to female ratio of 1.2 : 1. The median age at the time of diagnosis was 41 years (range 0-85). Males had a significant longer diagnostic delay if compared to females (9 vs. 3 months, respectively; p = 0.01). Direct immunofluorescence was positive in 94.7% of the patients, while duodenal biopsy showed partial to total villous atrophy in 70.1% of patients. All the females resulted positive to at least one of the antibodies tested, while a total of 12 male patients (10.5%) tested negative to celiac-specific antibodies. Female patients had a high rate (14.1%) of autoimmune thyroiditis., Conclusions: Our study confirmed some of the most relevant data regarding DH that have been previously reported in the literature. In addition, we found a reduced diagnostic delay in females with respect to males, possibly related to the higher sensitivity of serologic testing in females with DH compared to males. Finally, we demonstrated that intestinal involvement could be severe in patients with DH and that females should be tested for thyroiditis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Emiliano Antiga et al.)

Pemphigus is a life threatening autoimmune epidermal blistering disease involving skin and mucous membranes. Pemphigus usually affects middle age men and women involving oral mucosa first and then spreading on the skin. It is caused by the presence of autoantibodies (IgG and less frequently by IgA) directed against desmogleins, and/or other glycoproteins that plays a critical role in cell-cell attachment. Upon a predisposing genetic background, different agents have been shown to act as triggers for the pathogenesis of pemphigus. This guideline for the diagnosis and treatment of pemphigus has been developed by an Italian group of experts taking in account the Italian legislation and local pharmacological governance. Guidelines are adapted from the original article under the guidance of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. It summarizes evidence-based and expert-based recommendations (S2 level).

Clinical features and histological findings in bullous pemphigoid (BP) suggest a Th2-oriented inflammatory reaction, especially in the early stages of the disease. Elevated total serum IgE levels, blood eosinophilia, and elevated serum levels of different soluble inflammatory Th2 response mediators have been described in large cohorts of patients with classic clear-cut BP manifestations. Direct immunofluorescence, indirect immunofluorescence, and anti-BP230 and anti-BP180 IgE ELISA testing show self-reactive IgE autoantibodies in a consistent number of BP patients. Both IgE autoantibodies and a Th2-oriented immune response may play a role in the initial phases of BP and atypical cases of BP, such as severe erythematous and urticarial forms of BP, as well as blister formation. Two recently reported experimental murine models employing IgE autoantibodies against BP180 have been reported and the successful treatment of bullous pemphigoid with the anti-IgE antibody, omalizumab, supports the roles played by IgE autoantibodies in BP pathogenesis.

Background: Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae., Objectives: The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies., Methods: Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB)., Results: A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific., Conclusions: The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only., (© 2017 British Association of Dermatologists.)

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6β4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).

Epidermolysis bullosa acquisita is a rare autoimmune bullous disease characterized by the presence of circulating antibodies directed against the collagen type VII. Diagnosis is generally based on clinical history, clinical features, histology, direct and indirect immunofluorescence, immunoblotting and ELISA. Our study aims to determine the validity of the Biochip immunofluorescence microscopy for the serological diagnosis of epidermolysis bullosa acquisita. Six patients with epidermolysis bullosa acquisita and presence of antibodies against type VII collagen confirmed by ELISA were included in the study. Subsequently, all sera of patients were analyzed using Biochip. Antibodies anti-collagen type VII were detected in all sera by means of the Biochip technology. Thus, Biochip shows a good correlation with ELISA and seems to be an appropriate method for the diagnosis of epidermolysis bullosa acquisita. It is an easy, fast and standardized method which could facilitate the diagnosis of this autoimmune bullous disease. We suggest that it could be used as an initial screening test to identify patients with epidermolysis bullosa acquisita.

It is known that anti-Ro/SSA positivity leads to higher risk of miscarriage and fetal cardiac malformations. Particularly, anti-p200 antibodies against a finer specificity of the Ro/SSA antigen, have been associated with congenital heart block. The aim of the study was to assess the frequency of anti-p200 among female patients with different connective tissue diseases and, among these, the relevance of anti-p200 values in patients with cutaneous diseases compared to systemic diseases. Anti-p200 were investigated in 110 anti-Ro/SSA positive female sera, sent to our laboratory between 2008 and 2014 with suspect of connective disease, by using ELISA testing. Positivity was found in 40.9 % samples, 34 of them showed a strong positivity (values ≥ 1.0, cut off = 0.7). Patients with systemic diseases were anti-p200 positive in the 45.9 % of cases while patients with cutaneous diseases were positive in the 24.0 % of cases. Positivity for anti-p200 antibodies was revealed in 24.0 % of patients with discoid lupus erythematosus; 100 % of patients with dermatomyositis; 40.0 % of patients with mixed connective tissue disease; 25.0 % of patients with rheumatoid arthritis; 100 % of patients with Sjögren's syndrome; 33.3 % of patients with subacute cutaneous lupus erythematosus; 42.9 % of patients with systemic lupus erythematosus; 80.0 % of patients with systemic sclerosis. No significant difference in anti-p200 prevalence was found between systemic and cutaneous involvement, nevertheless, considering only positive sera, the antibody titer was higher in systemic diseases rather than in cutaneous diseases (2.6 ± 1.7 and 1.7 ± 1.9; p = 0.041). The authors think screenings for anti-Ro/SSA and anti-p200 antibodies should be included in the laboratory checklist for pregnancy.

Background: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune mucocutaneous bullous disease caused by autoantibodies against type VII collagen, a component of anchoring fibrils that stabilizes dermoepidermal adherence. Type VII collagen is composed of a collagenous domain linked by the noncollagenous (NC)1 and NC2 domains., Objectives:  To assess the repeatability, sensitivity and specificity of a recently developed enzyme-linked immunosorbent assay (ELISA) for detection of anti-type VII collagen autoantibodies, and to ascertain whether they may be a marker of disease activity in EBA., Methods: Using this ELISA, which was able to recognize autoantibodies against the NC1 and NC2 epitopes of type VII collagen, we tested 14 EBA sera, 30 healthy control sera and 113 disease control sera., Results: In the EBA sera group, 12 out of the 14 samples were positive in ELISA, with autoantibody titres varying from 7·2 to 127·9UmL(-1) (cutoff value <6), the sensitivity of the method being 86%. Among the controls, only two bullous pemphigoid sera tested positive, the specificity being 98·6%. A good correlation was found between EBA disease severity, expressed as autoimmune bullous skin disorder intensity score, and the serum levels of anti-collagen VII autoantibodies, measured by ELISA (n =14; r=0·965; P=0·0001). The intra- and interassay coefficients of variation of the ELISA method ranged from 6·3% to 18·3%., Conclusions:  This NC1+NC2 ELISA can be a practical assay for the diagnosis of EBA. The correlation between autoantibody titres and disease severity suggests its usefulness as a marker of disease activity in EBA However, this should be confirmed by studies on larger series of patients., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: The clinical phenotype of different forms of pemphigus is reportedly defined by the anti-desmoglein (Dsg) autoantibody profile. In routine practice, however, this is not always the case., Objectives: To verify the relationship between the anti-Dsg1 and -3 autoantibody profiles and titers on the one hand and the clinical phenotype and disease activity on the other., Materials and Methods: we followed-up clinically and serologically 20 pemphigus patients, including 3 mucosal pemphigus (mPV), 9 mucocutaneous pemphigus (mcPV), and 8 cutaneous pemphigus (PF)., Results: We found that the cutaneous and/or mucosal involvement and the autoantibody profile were only concordant in mPV patients. On the contrary, in other clinical forms this correlation was often absent., Conclusions: 1) The discrepancy between autoantibody profile and the clinical phenotype, at least in PF patients, appears to be due to non-pathogenic anti-Dsg3 antibodies; 2) in a proportion of patients the relationship between the Dsg1 and Dsg3 ELISA titers and the disease severity was absent; 3) in some patients, the anti-Dsg1 and -3 autoantibodies were lacking at diagnosis, suggesting a role of other antigens in the pathogenesis of the disease and, lastly, 4) the pure cutaneous and mucosal forms tend to respond more efficiently to the therapy than the mucocutaneous forms and have a persistent response.

Drug-induced pemphigus has been reported in patients receiving angiotensin-converting enzyme inhibitors. The aim of this work was to study a group of hypertensive patients without skin diseases treated with angiotensin-converting enzyme (ACE) Inhibitors (I), to verify the presence of serum circulating anti-antibodies. The indirect immunofluorescence showed that 33 sera (52.38%) presented autoantibodies directed to an antigen of the cytoplasm of the superficial epidermal keratinocytes. Two of the 33 positive sera had antibodies to Dsg1 and/or 3 in ELISA. Immunoblot analyses were negative. All the 48 control sera were found to have no circulating antibodies using the three assays. Our results would confirm that ACEI drugs may trigger the production of circulating autoantibodies also in patients without clinical manifestations of pemphigus.

A 7-year-old Caucasian girl had multiple bullae on the trunk, upper and lower limbs (Fig. 1a,b) for 10 days. The lesions were large, tense, and asymptomatic, and mucosae were not involved. Laboratory findings were all normal. Histopathology revealed a subepidermal blister containing numerous neutrophils, eosinophils, and fibrin. Direct immunofluorescence of perilesional skin disclosed linear deposition of IgA and slight linear deposits of IgM at the basement membrane zone (Fig. 2). Indirect immunofluorescence on monkey esophagus and on human salt-split skin was negative. Immunoblot assay (IB), performed with an epidermal extract, revealed IgA and IgG antibodies directed to BPAg2 antigen (Fig. 3), while it was negative when performed on dermal extract. Enzyme-linked immunosorbent serologic assay using a commercial kit (MBL, Naka-Ku Nagoya, Japan) with the noncollagenous domain (NC16A) of the BPAg2 antigen was negative for both IgA and IgG. A diagnosis of linear IgA disease (LAD) was made and a treatment with dapsone (50 mg/day) and prednisolone (30 mg/day) was initiated. One month later, lesions had cleared.

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating lesions in the folds and mouth and by the presence of autoantibodies against desmoglein 3. We describe two Caucasian patients with pemphigus vegetans, one of them presented antibodies to desmoglein 3 and 1 and the other one to desmoglein 3. Both patients also had circulating antibodies against a 190 kDa protein co-migrating with periplakin. Anti-periplakin reactivity is usually detected in paraneoplastic pemphigus, while it has never been reported in pemphigus vegetans. Our observation enlarges the spectrum of autoantibodies which may be associated with pemphigus vegetans. However, the pathophysiological significance of anti-periplakin reactivity in this pemphigus variant remains to be determined.

Mucous membrane pemphigoid (MMP) comprises a heterogenous group of autoimmune subepithelial bullous diseases very frequently having oral involvement. Very few studies have investigated the immunological status of a subset of MMP, termed oral pemphigoid (OP), presenting with exclusive oral lesions. In this study we show that 75% of 20 OP patients without scarring phenotype possessed circulating autoantibodies against the BP180 molecule, indicating a prominent role of this protein as a target antigen in OP. Of note, the frequency of reactivity against BP180 ectodomain epitopes in OP was similar to that previously reported for MMP with cicatricial phenotype, while the lack of significant recognition of BP180 intracellular domain appears to characterize OP with respect to other diseases of the pemphigoid group. Finally, the combined use of sensitive techniques allowed the detection of circulating autoantibodies in 90% of OP patients, supporting the usefulness of this approach in the diagnosis of MMP disease.

Background: Besides being present in paraneoplastic pemphigus (PNP), circulating antidesmoplakin (DP) antibodies have been found anecdotally in other bullous diseases, including pemphigus foliaceus and pemphigus vulgaris., Objectives: To verify how frequent anti-DP antibodies are in pemphigus vulgaris., Methods: We studied 48 sera from patients with proven pemphigus vulgaris (29 mucosal dominant pemphigus and 19 mucocutaneous pemphigus) by indirect immunofluorescence (IIF) with rat bladder epithelium (RBE) as a substrate and by immunoblotting (IB) on human keratinocyte cultures enriched in DP., Results: Ten sera (21%) were positive in IIF on RBE. By IB, eight sera proved to have antibodies to both DP I (250 kDa) and DP II (210 kDa), one serum had antibodies directed to DP I only, and two sera to DP II only., Conclusions: Our data confirm that RBE is not a specific IIF substrate for the serological diagnosis of PNP. It remains a sensitive and specific substrate for the detection of anti-DP antibodies, which, in patients with pemphigus vulgaris, are probably caused by an epitope-spreading phenomenon.

Background: Mucous membrane pemphigoid (MMP) includes a range of variants frequently having oral, particularly gingival, lesions. It has been suggested that MMP exclusively involving the oral cavity could be a distinct subset, but the immunological status of patients with predominantly oral lesions has received little attention., Methods: Indirect immunofluorescence (IIF) on normal human skin and normal human salt-split skin (SSS) as a substrate and immunoblotting on extracts of human keratinocyte cultures and normal human skin were carried out in 28 consecutive patients with MMP predominantly affecting the gingiva., Results: There was no significant difference between frequency of positive SSS-IIF among patients with exclusive oral lesions (42%) and with MMP not restricted to the oral cavity (78%) (P = 0.114). By immunoblotting, IgG of 13 sera (46%) reacted with the 180 kD bullous pemphigoid antigen (BPAg2), six (21%) reacted with the 230 kD bullous pemphigoid antigen (BPAg1), and two (7%) reacted with an antigen of 200 kD. IgA of three sera (11%) reacted with BPAg2 and three (11%) reacted with BPAg1. There was no significant difference between frequency of positive immunoblotting among patients with exclusive oral lesions (68%) and with MMP not restricted to the oral cavity (67%) (P = 1.00)., Conclusions: Most of the MMP sera contain IgG and IgA antibodies to the two major bullous pemphigoid antigens, independent of clinical presentation. Thus, in the majority of cases, patients with exclusively gingival pemphigoid lesions do not appear to have a distinct variety of mucous membrane pemphigoid.

Serological diagnosis of bullous pemphigoid is based on immunoblotting or indirect immunofluorescence on normal human salt-split skin. These methods are expensive or time-consuming and not available as a routine test in all laboratories. We used rat bladder epithelium as substrate for indirect immunofluorescence and compared it with other substrates and with immunoblotting. Twenty-nine bullous pemphigoid sera were studied on rat bladder epithelium, monkey oesophagus, salt-split skin and with immunoblotting on human keratinocyte cultures. Indirect immunofluorescence on rat bladder epithelium proved to be more sensitive (72%) than on monkey oesophagus alone (45%) and less sensitive than on salt-split skin (97%). Rat bladder epithelium, when tested on 41 sera of a control group, showed a very high specificity: 2/41 (95%). In combination with immunoblotting on keratinocyte extracts, indirect immunofluorescence on rat bladder epithelium allowed 93% of sera to be recognized, a value close to the salt-split skin alone. Rat bladder epithelium appears to be a more sensitive substrate than monkey oesophagus for the diagnosis of bullous pemphigoid and, although less specific, it is easier and faster than using salt-split skin, which remains indispensable to distinguish bullous pemphigoid from epidermolysis bullosa acquisita.

Bullous pemphigoid (BP) is unique among autoimmune skin diseases in which a high serum IgE level has been detected. We sought to determine the antigenic specificity of these IgE antibodies in 39 BP sera by immunofluorescence microscopy, immunoblot, and ELISA. The patient's sera contained IgG antibodies to 230-kDa (BP230) (n = 20), 180-kDa (BP180) (n = 9), and both BP230 and BP180 (n = 10) antigens. Serum IgE levels varied from 29 to 5000 kIU/L (mean +/- SD, 856 +/- 1426 kIU/L), among which sera containing IgG antibodies to BP230 had an IgE level on average 4.3 times higher than anti-BP180 sera. IgE antibodies in 18 sera were found to be autoantibodies reactive either with an epidermal component of basement membrane zone by immunofluorescence microscopy on 1 M NaCl-split skin or with a 230-kDa antigen by immunoblots of cultured human keratinocytes. The 230-kDa epidermal antigen recognized by IgE antibodies comigrated with the BP230 as labeled by a specific human monoclonal antibody. IgE anti-BP230 antibodies in patients' sera were always associated with IgG autoantibodies. No sera contained IgE antibodies to BP180 or to any other epidermal or dermal antigens as verified by immunoblot and ELISA. A good correlation was found between the presence of IgE circulating autoantibodies and the level of serum IgE (P < 0.004). IgE antibodies to BP230, like IgG autoantibodies, were mapped primarily to the C-terminal end of the protein, as they labeled rBP55, a BP230 recombinant protein encoded by a cDNA for the C-terminal end of BP230.

We report changes in the antigen recognition pattern of sera from two pemphigus foliaceus patients with a long-term follow-up. The patients' sera were analysed by immunoblotting using different antigenic sources: cultured human keratinocytes, bovine tongue epithelium and a recombinant protein corresponding to the C-terminal end of the 230-kDa bullous pemphigoid antigen. While initial serum samples reacted exclusively with the 160-kDa desmoglein 1, the later sera reacted both with desmoglein 1 and a 190-kDa antigen immunolocalized to the desmosomal plaque, previously demonstrated to be recognized by sera of some patients with paraneoplastic pemphigus. IgG subclass analysis further showed that antidesmoglein 1 antibodies were of IgG1 and/or IgG4 subclasses, while anti-190-kDa antibodies were IgG3. The patients were free of malignancy.

The sera of 263 patients with bullous pemphigoid (BP) were tested by indirect immunofluorescence (IIF) on salt-split skin (SSS) and immunoblot (IB) assay, in order to assess the diagnostic sensitivity of these techniques. Among the 263 sera tested, 198 sera (75%) contained antibasement membrane zone antibodies demonstrable by IIF reacting to the epidermal (98%) or both the dermal and epidermal sides (2%) of SSS. One hundred and eighty-two of the 263 sera (69%) reacted by IB with BP antigens (Ag), most commonly the BPAg1 (93 cases, 51%), and a complex of BPAg1 and the 180 kDa minor BP antigen (BPAg2) (47 cases, 26%). BPAg2 alone was found in 42 cases (23%). A good correlation was found between the detection of autoantibodies by IIF and labelling of BPAg1 and/or BPAg2 by IB assay, in which 152 of 198 sera with an epidermal pattern in IIF identified a BP antigen. IB analysis of the 65 sera negative by IIF yielded positive results in 30 cases (46%). Thirty-one percent (13 of 42) of sera recognizing by IB BPAg2, were negative by IIF, as compared with 12% (11 of 93) of those recognizing BPAg1 (P < 0.01). Comparing the sensitivity of the two tests, IIF (75%) was found to be more sensitive than IB (69%). Thirty-five of the 263 sera (13%) remained negative by both techniques. It can be concluded from this study that IIF on SSS appears to be a sensitive and reliable assay for screening BP; IB should be performed for the sera that are negative by IIF as it may reveal circulating antibodies, particularly to BPAg2.

In a family of four children (two boys and two girls), the two brothers had severe, protracted watery diarrhea beginning at 2 and 3 weeks of life, respectively. Duodenal mucosa in both patients showed total villous atrophy and severe inflammatory infiltration of the entire bowel. The first patient also had lymphoid cell infiltration of the pancreas and died at 6 weeks of age. The second boy is alive at 2 years of age and is immunocompetent, but still receives total parenteral nutrition. Indirect immunofluorescence studies revealed circulating antibodies to enterocytes, smooth muscle, thyroid, and islet cells. Bullous pemphigoid antibodies (230 and 180 kd), specific for hemidesmosomal proteins and usually associated with a subepidermal blistering skin disease, were detected by direct and indirect immunofluorescence studies and by Western immunoblot. A diagnosis of autoimmune hepatitis was made, based on evidence of chronic active hepatitis and circulating anti-smooth muscle antibody. Immunosuppressive treatments induced partial clinical remission of the diarrhea but no resolution of the small bowel injury. At 16 months of age, remission of the diarrhea occurred, but persistent autoimmune hepatitis led us to maintain treatment with prednisone and azathioprine, and later with cyclosporine. In this child, as in other patients with autoimmune disease, the link between autoantibodies and organ damage remains uncertain but immunosuppressive treatment is indicated.

We describe a patient with a papulovesicular eruption associated with scarring and severe mucosal lesions that led to blindness. Direct immunofluorescence showed linear IgA deposits at the dermoepidermal junction. Indirect immunofluorescence microscopy showed that the patient's serum reacted with the dermal side of salt-split skin. Direct immunoelectron microscopy showed the IgA deposits to be associated with anchoring fibrils, whereas with Western blot analysis the patient's serum reacted with a 290 kd dermal antigen. On the basis of these findings, we suggest that our case may represent a form of IgA-mediated epidermolysis bullosa acquisita.

Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease defined on the basis of direct immunofluorescence findings. However, more recent techniques used to study bullous dermatoses suggest that LABD may be heterogeneous. A patient with LABD of childhood (chronic benign disease of childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. This young girl's periorificial (mouth, genitalia), erythematovesicular lesions were diagnosed initially as herpes simplex. Histologic examination revealed eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA autoantibodies that reacted with the epidermal side of salt-split skin; these reacted by Western blot with a 230 kDa epidermal antigen, as in bullous pemphigoid. This case, fulfilling the diagnostic clinical and direct immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.

Background: Anti‐nuclear antibodies (ANA), anti‐extractable nuclear antigens (ENA) and anti‐dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case‐series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. Objective: To characterize the correlations between CLE subtypes as well as LE‐non‐specific skin lesions and their autoantibody pattern. Methods: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE‐non‐specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. Results: Anti‐nuclear antibodies (P < 0.0001), anti‐dsDNA (P < 0.0001), ENA (P = 0.001), anti‐Sm (P = 0.001), anti‐RNP (P = 0.004) and anti‐histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti‐dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti‐dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti‐Ro/SSA (OR = 0.49, P < 0.0001) and anti‐dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti‐Ro/SSA (OR = 3.83, P < 0.0001), anti‐Smith (OR = 2.95, P = 0.004) and anti‐RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti‐dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE‐non‐specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti‐Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. Conclusion: According to our findings, some well‐known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE‐non‐specific skin lesions was highlighted. A strict association between anti‐ENA and anti‐Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced. [ABSTRACT FROM AUTHOR]