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BACKGROUND: Interest in the use of omalizumab to treat bullous pemphigoid (BP) in the event of resistance or contraindication to conventional therapies is currently based on limited evidence. OBJECTIVES: To assess the effectiveness and safety of omalizumab in BP and to identify predictive factors in response to treatment. METHODS: We conducted a French national multicentre retrospective study including patients with a confirmed diagnosis of BP treated with omalizumab after failure of one or several treatment lines. We excluded patients with clinically atypical BP, as per Vaillant's criteria. The criteria for clinical response to omalizumab were defined according to the 2012 international consensus conference. Anti-BP180-NC16A IgE enzyme-linked immunosorbent assay was performed on sera collected before initiating omalizumab, when available. RESULTS: Between 2014 and 2021, 100 patients treated in 18 expert departments were included. Median age at diagnosis was 77â years (range 20-98). Complete remission (CR) was achieved in 77% of patients, and partial remission in an additional 9%. CR was maintained 'off therapy' in 11.7%, 'on minimal therapy' in 57.1%, and 'on non-minimal therapy' in 31.2%. Median time to CR was 3â months (range 2.2-24.5). Relapse rate was 14%, with a median follow-up time of 12â months (range 6-73). Adverse events occurred in four patients. CR was more frequently observed in patients with an increased serum baseline level of anti-BP180-NC16A IgE (75% vs. 41%; P = 0.011). Conversely, urticarial lesions, blood total IgE concentration or eosinophil count were not predictive of CR. Patients with an omalizumab dosage > 300â mg every 4 weeks showed a similar final outcome to those with a dosage ≤ 300â mg every 4 weeks, but control of disease activity [median 10â days (range 5-30) vs. 15â days (range 10-60); P < 0.001] and CR [median 2.4â months (range 2.2-8.2) vs. 3.9â months (range 2.3-24.5); P < 0.001] were achieved significantly faster. CONCLUSIONS: We report the largest series to date of BP treated by omalizumab and confirm its effectiveness and safety in this indication. Serum baseline level of anti-BP180-NC16A IgE may predict response to treatment.
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Penfigoide Ampolloso , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Penfigoide Ampolloso/diagnóstico , Colágeno Tipo XVII , Omalizumab/uso terapéutico , Estudios Retrospectivos , Colágenos no Fibrilares , Autoantígenos , Inmunoglobulina E , AutoanticuerposRESUMEN
Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.
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Enfermedad de Castleman , Miastenia Gravis , Síndromes Paraneoplásicos , Pénfigo , Humanos , Pénfigo/diagnóstico , Pénfigo/etiología , Enfermedad de Castleman/patología , Autoanticuerpos , Miastenia Gravis/diagnóstico , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/diagnósticoRESUMEN
Several reports have highlighted a potential role of autoreactive B-cells and autoantibodies that correlates with increased disease severity in patients with idiopathic pulmonary fibrosis (IPF). Here we show that patients with IPF have an altered B-cell phenotype and that those subjects who have autoantibodies against the intermediate filament protein periplakin (PPL) have a significantly worse outcome in terms of progression-free survival. Using a mouse model of lung fibrosis, we demonstrate that introducing antibodies targeting the endogenous protein PPL (mimicking naturally occurring autoantibodies seen in patients) directly in the lung increases lung injury, inflammation, collagen and fibronectin expression through direct activation of follicular dendritic cells, which in turn activates and drives proliferation of fibroblasts. This fibrocyte population was also observed in fibrotic foci of patients with IPF and was increased in peripheral blood of IPF patients compared to aged-matched controls. This study reiterates the complex and heterogeneous nature of IPF, identifying new pathways that may prove suitable for therapeutic intervention.
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Autoanticuerpos , Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Pulmón/metabolismo , Progresión de la Enfermedad , Fibroblastos/metabolismoRESUMEN
AIMS: Linear immunoglobin A (IgA) bullous dermatosis is a rare autoimmune dermatosis considered spontaneous or drug-induced (DILAD). We assessed all DILAD cases, determined the imputability score of drugs and highlighted suspected drugs. METHODS: Data for patients with DILAD were collected retrospectively from the French Pharmacovigilance network (from 1985 to 2017) and from physicians involved in the Bullous Diseases French Study Group and the French Investigators for Skin Adverse Reactions to Drugs. Drug causality was systematically determined by the French imputability method. RESULTS: Of the 69 patients, 42% had mucous membrane involvement, 20% lesions mimicking toxic epidermal necrolysis (TEN), 21% eosinophil infiltrates and 10% keratinocytes necrosis. Direct immunofluorescence, in 80%, showed isolated linear IgA deposits. Vancomycin (VCM) was suspected in 39 cases (57%), 11 had TEN-like lesions, as compared with three without VCM suspected. Among the 33 patients with a single suspected drug, 85% had an intrinsic imputability score of I4. Among them, enoxaparin, minocycline and vibramycin were previously unpublished. For all patients, the suspect drug was withdrawn; 15 did not receive any treatment. First-line therapy for 31 patients was topical steroids. Among the 60 patients with available follow-up, 52 achieved remission, 10 without treatment. Four patients experienced relapse, four died and five had positive accidental rechallenges. CONCLUSIONS: There is no major clinical difference between DILAD and idiopathic linear IgA bullous dermatosis, but the former features a higher prevalence of patients mimicking TEN. VCM, suspected in more than half of the cases, might be responsible for more severe clinical presentations. We report three new putative drugs.
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Monitoreo de Drogas/estadística & datos numéricos , Dermatosis Bullosa IgA Lineal/epidemiología , Farmacovigilancia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Bases de Datos Factuales/estadística & datos numéricos , Diagnóstico Diferencial , Doxiciclina/efectos adversos , Enoxaparina/efectos adversos , Femenino , Francia/epidemiología , Humanos , Dermatosis Bullosa IgA Lineal/inducido químicamente , Dermatosis Bullosa IgA Lineal/diagnóstico , Masculino , Persona de Mediana Edad , Minociclina/efectos adversos , Prevalencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndrome de Stevens-Johnson/diagnóstico , Vancomicina/efectos adversos , Adulto JovenRESUMEN
The role of autoimmunity targeting epithelial antigens in asthma has been suggested, in particular in non-atopic and severe asthma. Periplakin, a desmosomal component, is involved in epithelial cohesion and intracellular signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients with asthma, with no association with severity or atopy. In addition, anti-periplakin IgE antibodies were detected in 12 of 138 tested patients (8.7 %) and were more frequently observed in patients with than without nasal polyposis. This study identifies a new autoimmune epithelial target in asthma. Whether periplakin autoimmunity (both IgG and IgE auto-antibodies) is involved in asthma pathogenesis remains to be studied during the disease course of these patients.
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Asma/inmunología , Autoanticuerpos/sangre , Autoinmunidad , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Plaquinas/inmunología , Adulto , Asma/sangre , Asma/diagnóstico , Asma/epidemiología , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/sangre , Pólipos Nasales/epidemiología , Pólipos Nasales/inmunología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Estudios Seroepidemiológicos , Pruebas Serológicas , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Serologic diagnosis of epidermolysis bullosa acquisita (EBA) relies on the detection of circulating autoantibodies to type VII collagen (C7). OBJECTIVE: We sought to compare the diagnostic performances of a commercialized enzyme-linked immunosorbent assay (ELISA) using C7 noncollagenous (NC) domains (C7-NC1/NC2 ELISA) and indirect immunofluorescence (IIF) biochip test on NC1-C7-expressing transfected cells (IIFT), with a full-length-C7 ELISA developed in our laboratory. METHODS: C7-NC1/NC2 ELISA, IIFT, and full-length-C7 ELISA were run on 77 nonselected consecutive EBA sera. RESULTS: C7-NC1/NC2 ELISA, IIFT, and full-length-C7 ELISA were positive, respectively, for: 30%, 27%, and 65% of the 77 sera; 43%, 32%, and 80% of 44 sera labeling the salt-split-skin (SSS) floor (F) by IIF (SSS/F(+)); 9%, 22%, and 47% of 32 SSS/F(-) sera; 28%, 28%, and 58% of classic EBA; 41%, 41%, and 82% of inflammatory EBA; and 18%, 0%, and 55% of mucous-membrane-predominant EBA. Significant differences for all sera were found between: the 2 ELISAs for the 77 sera, SSS/F(+) and SSS/F(-) sera, and IIFT versus full-length-C7 ELISA. LIMITATIONS: The retrospective design was a limitation. CONCLUSION: C7-NC1/NC2 ELISA and IIFT sensitivities for serologic diagnoses of EBA were low. Full-length-C7 ELISA was significantly more sensitive and could serve as a reference test.
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Autoanticuerpos/sangre , Colágeno Tipo VII/inmunología , Epidermólisis Ampollosa Adquirida/sangre , Epidermólisis Ampollosa Adquirida/diagnóstico , Pruebas Serológicas/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Persona de Mediana Edad , Análisis por Matrices de Proteínas , Curva ROC , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Lichen planus pemphigoides (LPP), an association between lichen planus and bullous pemphigoid lesions, is a rare subepithelial autoimmune bullous disease. Mucous membrane involvement has been reported previously; however, it has never been specifically studied. Methods: We report on 12 cases of LPP with predominant or exclusive mucous membrane involvement. The diagnosis of LPP was based on the presence of lichenoid infiltrates in histology and immune deposits in the basement membrane zone in direct immunofluorescence and/or immunoelectron microscopy. Our systematic review of the literature, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, highlights the clinical and immunological characteristics of LPP, with or without mucous membrane involvement. Results: Corticosteroids are the most frequently used treatment, with better outcomes in LPP with skin involvement alone than in that with mucous membrane involvement. Our results suggest that immunomodulators represent an alternative first-line treatment for patients with predominant mucous membrane involvement.
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Liquen Plano , Membrana Mucosa , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corticoesteroides/uso terapéutico , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Liquen Plano/inmunología , Liquen Plano/diagnóstico , Membrana Mucosa/patología , Membrana Mucosa/inmunología , Penfigoide Ampolloso/inmunología , Penfigoide Ampolloso/tratamiento farmacológico , Penfigoide Ampolloso/patología , Penfigoide Ampolloso/diagnósticoRESUMEN
OBJECTIVES: To compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and to study the relationship between ACPA and disease activity. METHODS: A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed. RESULTS: At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47-48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria. CONCLUSIONS: In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.
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Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Diagnóstico Precoz , Fibrinógeno/inmunología , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Citrulina/metabolismo , Femenino , Francia , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Sensibilidad y Especificidad , Vimentina/inmunologíaAsunto(s)
Neoplasias Ováricas/radioterapia , Síndromes Paraneoplásicos/fisiopatología , Pénfigo/etiología , Radiodermatitis/diagnóstico , Biopsia con Aguja , Diagnóstico Diferencial , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Resultado Fatal , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Neoplasias Ováricas/patología , Cuidados Paliativos/métodos , Síndromes Paraneoplásicos/tratamiento farmacológico , Pénfigo/tratamiento farmacológico , Pénfigo/patología , Radiodermatitis/tratamiento farmacológico , Medición de RiesgoRESUMEN
RATIONALE: Injury to alveolar epithelial cells is central to the pathophysiology of idiopathic pulmonary fibrosis (IPF). An abnormal autoimmune response directed against antigens of the alveolar epithelium may contribute to the disease. OBJECTIVES: To detect circulating autoantibodies (autoAbs) directed against epithelial structures. METHODS: We performed immunoblot by separating human placental amnion extract or alveolar epithelial cell (A549 cell line) proteins on polyacrylamide gels, blotting on nitrocellulose membranes, and incubating with serum from patients with IPF (n = 40) or healthy subjects (n = 40). Proteomic analysis and mass spectrometry characterized the target protein. Inhibition experiments performed with the correspondent recombinant protein confirmed our results. MEASUREMENTS AND MAIN RESULTS: We identified IgG autoAbs recognizing a 200-kD protein in the serum of patients with IPF. Proteomic analysis identified this protein as human periplakin (PPL), a component of desmosomes. Anti-PPL Abs were found by immunoblot in both serum and bronchoalveolar lavage in patients with IPF: 16/40 (40%) of them were positive versus none of the control subjects. Immunohistochemistry revealed that PPL was strongly expressed in bronchial and alveolar epithelium, but that PPL exhibited changes in intracellular localization among normal and fibrotic alveolar epithelium. In an alveolar epithelial wound repair assay, an anti-PPL IgG decreased cell migration. Recombinant PPL induced bronchoalveolar lavage T lymphocyte proliferation. Patients with IPF with anti-PPL Abs had a more severe respiratory disease, despite no difference in survival. CONCLUSIONS: We found a new circulating autoAb directed against PPL in patients with IPF, associated with a more severe disease.
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Autoanticuerpos/sangre , Autoinmunidad , Fibrosis Pulmonar Idiopática/inmunología , Inmunoglobulina G/sangre , Plaquinas/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Persona de Mediana Edad , Mucosa Respiratoria/inmunología , Índice de Severidad de la EnfermedadRESUMEN
The role of IgE autoantibodies has been demonstrated in the pathogenesis of bullous pemphigoid for many years. Recently, omalizumab (OMZ), a humanized monoclonal anti-IgE antibody that depletes total serum IgE, has been used off-label in a few case series of bullous pemphigoids demonstrating a rapid efficacy and allowing significant improvements or complete remission as add-on therapy in first-line treatment-resistant patients. Herein, we report the largest retrospective study to evaluate OMZ effectiveness in patients with subepidermal autoimmune blistering diseases. Our series included 13 patients from a single center with bullous pemphigoid or mucous membrane pemphigoid, of whom 7 had mucous membrane involvement. OMZ was added to the unchanged immunosuppressive therapies. Detailed clinical and immunological data during the first year were collected, notably for specific anti-BP180-NC16A IgE and IgG, and the median total follow-up was 30 months (range: 3-81). Our series demonstrated that OMZ induced a significant improvement in pruritus, urticarial score, and daily blister count on day 15, allowing disease control to be achieved in a 1-month median time and complete remission (CR) in a 3-month median time in 85% of these patients previously in therapeutic impasse. At the end of the follow-up, 31% of patients achieved CR on minimal therapy after OMZ weaning without relapses, and 54% achieved CR on OMZ continuation with a minimal dose of concomitant treatment. Two patients experienced therapeutic failure (15%). At baseline, clinical variables reflecting activity were significantly positively correlated with eosinophil blood count, total IgE serum level, specific anti-BP180 IgE and IgG. While baseline anti-BP180 IgG and specific anti-BP180 IgE were significantly positively correlated, only the two patients who experienced a therapeutic failure with OMZ did not fit with this correlation, demonstrating elevated levels of anti-BP180 IgG with no measurable BP180-specific IgE. Follow-up of immunological variables demonstrated a rapid decrease of eosinophilia towards normalization, whereas a slower decline towards negativation was observed over 1 year for anti-BP180 IgG and anti BP180 IgE in patients who responded to OMZ. This case series demonstrated that OMZ is a rapidly effective biologic therapy for refractory bullous pemphigoid and mucous membrane pemphigoid, permitting rapid disease control and reduction of concomitant therapeutics.
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Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Autoantígenos , Humanos , Inmunoglobulina E , Inmunoglobulina G , Colágenos no Fibrilares , Omalizumab/uso terapéutico , Estudios RetrospectivosRESUMEN
Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, chronic, subepithelial autoimmune blistering diseases (AIBDs) with predominant involvement of mucous membranes that can be sight-threatening and life-threatening. Rituximab (RTX) has demonstrated its efficacy in severe MMP refractory to conventional immunosuppressants in small series that differed in RTX scheme, concomitant therapies, and outcome definitions. In a meta-analysis involving 112 patients with MMP treated with RTX, complete remission (CR) was reported in 70.5% of cases. Herein, we report the largest retrospective monocentric study on RTX efficacy in a series of 109 severe and/or refractory patients with MMP treated with RTX with a median follow-up period of 51.4 months. RTX was administered in association with immunomodulatory drugs (dapsone, salazopyrine) without any other systemic immunosuppressant in 104 patients. The RTX schedule comprised two injections (1 g, 2 weeks apart), repeated every 6 months until CR or failure, with a unique consolidation injection (1 g) after CR. The median survival times to disease control and to CR were 7.1 months and 12.2 months, respectively. The median number of RTX cycles required to achieve CR in 85.3% of patients was two. The larynx was the lesional site that took the longest time to achieve disease control. One year after RTX weaning, CR off RTX was obtained in 68.7% of cases. CR off RTX with only minimum doses of immunomodulatory drugs was achieved in 22.0% of patients. Further, 10.1% of patients were partial responders and 4.6% were non-responders to RTX. Relapse occurred in 38.7% of cases, of whom 91.7% had achieved CR again at the last follow-up. In MMP, CR was achieved in a longer time and after more rituximab cycles than in pemphigus, especially for patients with MMP with anti-type VII collagen reactivity. RTX with concomitant immunomodulatory drugs was not responsible for an unusual proportion of adverse events. This large study confirms that RTX is an effective therapy in patients with severe and/or refractory MMP, corroborating previous findings regarding the effects of RTX on AIBDs such as pemphigus.
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Enfermedades Autoinmunes , Penfigoide Benigno de la Membrana Mucosa , Penfigoide Ampolloso , Pénfigo , Enfermedades Autoinmunes/terapia , Vesícula/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Membrana Mucosa , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Pénfigo/tratamiento farmacológico , Estudios Retrospectivos , Rituximab/uso terapéutico , Resultado del TratamientoRESUMEN
A 64-year-old patient developed a widespread autoimmune mucocutaneous blistering disease 3 weeks after the initiation of the anti-programmed death-1 (anti-PD-1) pembrolizumab therapy administered for a locally advanced cutaneous squamous cell carcinoma (SCC) of the buttocks arising from hidradenitis suppurativa. A diagnosis of paraneoplastic pemphigus (PNP) was made based on the presence of a suprabasal acantholysis associated with intercellular deposits of immunoglobulin G and C3 on basement membrane zone. Analysis of the patient's sera was positive on monkey bladder and detected circulating antibodies against desmoglein 3 and desmoplakin I prior to the initiation of pembrolizumab. At that time, the patient had few localized blisters limited to the peri-tumoral skin of the buttocks with acantholysis but without in vivo immune deposits. Pembrolizumab therapy was discontinued and a complete remission of PNP was obtained using oral steroids. Reintroduction of pembrolizumab resulted in flare of PNP. Given the close temporal relation between pembrolizumab initiation and the subsequent clinical expression of a widespread PNP, the patient was diagnosed with pre-existing subclinical PNP exacerbated by PD-1 inhibitor. The extreme rarity of PNP in the setting of cutaneous SCC and the effects of challenge, dechallenge, and rechallenge of pembrolizumab argue in favor of a checkpoint inhibitor related adverse effect. Our case is the first PNP associated with anti-PD-1 therapy and serological follow-up suggest that one infusion of pembrolizumab is sufficient to allow clinical expression of underlying pemphigus auto-immunity.
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BACKGROUND: Bullous systemic lupus erythematosus (BSLE) is a rare blistering condition associated with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: We conducted a multi-center retrospective study and literature review in order to describe the clinical, immunological, and histological presentations and outcomes of BSLE. The skin biopsies were centrally reviewed, and sera obtained during a flare of BSLE were analyzed for identification of circulating anti-basement membrane zone antibodies. RESULTS: Ten patients (all women, median age at SLE diagnosis of 22 years) were included, as well as 118 cases from a systematic review of the literature. Lupus nephritis was associated in 50% of the cases. BSLE presented as tensed bullae on normal or erythematous skin, predominantly localized on the trunk, arms, head, and neck. Urticarial lesions were associated in 31% of the cases, and mucous membrane involvement was seen in 51%. Histological analyses displayed subepidermal detachment, dermal infiltration of polynuclear neutrophils, alignment of these cells at the basal membrane zone and leukocytoclasis. The direct immunofluorescence was polymorphic, showing linear and/or granular deposits of IgG, IgA, IgM, and/or C3. Anti-type VII collagen antibodies were detected in 69% of cases. Dapsone was efficacious in 90% of cases. CONCLUSION: BSLE is rather an autoimmune neutrophilic blistering disease associated with SLE than a cutaneous manifestation and may be associated with active extra-cutaneous manifestations of SLE. Dapsone is the first-choice option.
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Vesícula/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Piel/patología , Adulto , Antiinfecciosos , Vesícula/tratamiento farmacológico , Vesícula/patología , Dapsona/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/patología , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Familial pseudohyperkalaemia (FP) is a symptomless, dominantly inherited red cell trait, which shows a 'passive leak' of K+ cations into the plasma upon storage of blood at room temperature (or below). There are no haematological abnormalities. The loss of K+ is due to a change in the temperature dependence of the leak. The Scottish case initially described, FP Edinburgh, maps to 16q23-qter. Here we studied a large kindred of Flemish descent with FP, termed FP Lille, which was phenotypically identical to the Edinburgh FP. In FP Lille, however, the responsible locus mapped to 2q35-36, with a Lod score of 8.46 for marker D2S1338. We infer that FP Edinburgh and FP Lille, although they are phenocopies of one another, stem from two distinct loci, FP1 (16q23-qter) and FP2 (2q35-36), respectively. This duality hints at the possibility that the protein mediating the leak might be a heterodimer. No mutation was found in three plausibly candidate genes: the KCNE4 gene, the TUBA1 gene and a predicted gene located in genomic contig NT_005403.
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Cromosomas Humanos Par 2 , Eritrocitos/metabolismo , Enfermedades Hematológicas/genética , Potasio/metabolismo , Mapeo Cromosómico , Femenino , Haplotipos , Enfermedades Hematológicas/metabolismo , Humanos , Masculino , LinajeAsunto(s)
Anticuerpos Anticardiolipina/sangre , Anticuerpos Antifosfolípidos/sangre , Sangre Fetal/inmunología , beta 2 Glicoproteína I/inmunología , Adulto , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Recién Nacido , Persona de Mediana Edad , Embarazo , Valores de Referencia , Reproducibilidad de los ResultadosAsunto(s)
Eritema Multiforme/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Lenalidomida/uso terapéutico , Adulto , Enfermedad Crónica , Sustitución de Medicamentos , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Lenalidomida/efectos adversos , Recurrencia , Talidomida/efectos adversosRESUMEN
BACKGROUND: Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFalpha antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy. METHODS: Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined. RESULTS: At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p<0.001), whereas anti-CCP showed little change (p=0.053). ANA titres increased significantly (p<0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16-3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16-4.13]). CONCLUSIONS: During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.
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Anticuerpos Antinucleares/sangre , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Péptidos Cíclicos/inmunología , Factor Reumatoide/sangre , Artritis Reumatoide/inmunología , Artritis Reumatoide/fisiopatología , Quimioterapia Combinada , Femenino , Estado de Salud , Humanos , Infliximab , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
INTRODUCTION: Autoantibodies against C1q correlate with lupus nephritis. We compared titers of anti-C1q and anti-dsDNA in 70 systemic lupus erythematosus patients with (n = 15) or without (n = 55) subsequent biopsy-proven lupus nephritis. METHODS: The 15 patients with subsequent lupus nephritis had anti-C1q assays during clinical flares (mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), 10.0 +/- 4.7; range, 3 to 22) before the diagnosis of lupus nephritis (median, 24 months; range 3 to 192). Among the 55 others, 33 patients had active lupus (mean SLEDAI, 10.3 +/- 6.2; range, 4 to 30) without renal disease during follow-up (median 13 years; range 2 to 17 years) and 22 had inactive lupus (mean SLEDAI, 0; range, 0 to 3). RESULTS: Anti-C1q titers were elevated in 15/15 (100%) patients who subsequently developed nephritis (class IV, n = 14; class V, n = 1) and in 15/33 (45%) patients without renal disease (P < 0.001). The median anti-C1q titer differed significantly between the groups (P = 0.003). Anti-C1q titers were persistently positive at the time of glomerulonephritis diagnosis in 70% (7/10) of patients, with no difference in titers compared with pre-nephritis values (median, 147 U/ml; interquartile range (IQR), 69 to 213 versus 116 U/ml; 50 to 284, respectively). Titers decreased after 6 months' treatment with immunosuppressive drugs and corticosteroids (median, 76 U/ml; IQR, 33 to 106) but remained above normal in 6/8 (75%) patients. Anti-dsDNA antibodies were increased in 14/15 (93.3%) patients with subsequent nephritis and 24/33 (72.7%) patients without nephritis (P = ns). Anti-C1q did not correlate with anti-dsDNA or the SLEDAI in either group. CONCLUSIONS: Anti-C1q elevation had 50% positive predictive value (15/30) and 100% (18/18) negative predictive value for subsequent class IV or V lupus nephritis.
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Autoanticuerpos/biosíntesis , Complemento C1q/inmunología , Glomerulonefritis/inmunología , Lupus Eritematoso Sistémico/inmunología , Adolescente , Adulto , Anciano , Autoanticuerpos/sangre , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Glomerulonefritis/diagnóstico , Glomerulonefritis/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Nefritis Lúpica/clasificación , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA. METHODS: We studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry. RESULTS: In accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy. CONCLUSIONS: Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.