RESUMEN
BACKGROUND: Hydroxychloroquine (HCQ) has been positioned as an anchor drug for systemic lupus erythematosus (SLE). There is evidence supporting the benefits of HCQ; however, the effect of additional HCQ in maintenance therapy remains unclear. METHODS: Thirty patients with SLE who visited Juntendo University Hospital were receiving maintenance therapy before HCQ treatment and were able to complete more than 104 weeks of HCQ treatment were analyzed. Anti-DNA antibody titers, IgG and CH50 levels, the maintenance dose of corticosteroids, the SLE disease activity index (SLEDAI), and the achievement of the Lupus Low Disease Activity State (LLDAS) were evaluated at baseline and at 12, 24, 52, and 104 weeks after HCQ initiation. RESULTS: We observed improvements in the anti-DNA antibody titers, IgG and CH50 levels, maintenance dose of corticosteroids, and SLEDAI at week 104 relative to baseline. Moreover, the LLDAS achievement rate increased over time from 10% at baseline to 43% and 80% at week 52 and week 104, respectively. CONCLUSION: Two years of continuous HCQ treatment led to improvements in SLE disease activity and corticosteroid dose and an increase in LLDAS achievement, thereby demonstrating the significance of the maintenance dose of HCQ for the management of SLE.
Asunto(s)
Antirreumáticos/uso terapéutico , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Anticuerpos Antinucleares/sangre , Ensayo de Actividad Hemolítica de Complemento , Femenino , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulina G/sangre , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). METHODS: Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). RESULTS: Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. CONCLUSION: Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.
Asunto(s)
Autoanticuerpos/sangre , Interferones/sangre , Interleucina-17/sangre , Lupus Eritematoso Cutáneo/sangre , Lupus Eritematoso Cutáneo/inmunología , Adulto , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Inmunohistoquímica , Interferones/inmunología , Interleucina-17/inmunología , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/metabolismoRESUMEN
BACKGROUND: Linear cutaneous lupus erythematosus is a rare subtype of lupus erythematosus (LE) that develops linear lesions following the lines of Blaschko. Linear cutaneous lupus erythematosus may present as various subtypes of LE, including linear discoid lupus erythematosus. There are few reports about pigmentedlinear discoid lupus erythematosus in the literature. AIMS: We aimed to summarize the clinical and pathological features of patients with pigmented linear discoid lupus erythematosus following the lines of Blaschko. METHODS: Eighteen patients with pigmented linear discoid lupus erythematosus attending the outpatient department of the Dermatology, Peking Union Medical College Hospital, China, were enrolled in the study. We recorded clinical data including sex, age at onset, disease duration, location and distribution of the lesions, symptoms, trigger factors, antinuclear antibody (ANA) testing, therapy, and therapeutic responses. Histopathological features were also summarized. RESULTS: All 18 patients presented with well-defined brownish pigmented linear or segmental macules or plaques, following the lines of Blaschko. All the lesions were located on the head or neck. Unilaterally distributed lesions were found in 94.4% of patients. Two patients showed low titers of ANA in a speckled pattern. No systemic involvement or progression to systemic LE was noted. The patients were clinically diagnosed as pigmented lichen planus (55.6%), pigmented linear discoid lupus erythematosus (33.3%), and linear morphea (11.1%) before histopathological examination. LIMITATIONS: The study was retrospective and direct immunofluorescence was not performed. Not all patients' information was available and 4 patients were lost to follow-up because their contact information was changed. CONCLUSION: Pigmented linear discoid lupus erythematosus mostly occurs on the head and neck. It manifests as brownish macules along the lines of Blaschko. Differentiation between pigmented linear discoid lupus erythematosus and other dermatoses that have a linear distribution can be difficult both clinically and pathologically, but histological details can help distinguish them.
Asunto(s)
Lupus Eritematoso Discoide/patología , Trastornos de la Pigmentación/patología , Adolescente , Adulto , Anticuerpos Antinucleares/sangre , Niño , China , Femenino , Cabeza , Humanos , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Discoide/terapia , Masculino , Persona de Mediana Edad , Cuello , Trastornos de la Pigmentación/sangre , Trastornos de la Pigmentación/etiología , Trastornos de la Pigmentación/terapia , Estudios RetrospectivosRESUMEN
Systemic lupus erythematosus (SLE) impacts multiple organ systems, although the causes of many individual SLE pathologies are poorly understood. This study was designed to elucidate organ-specific inflammation by identifying proteins that correlate with SLE organ involvement and to evaluate established biomarkers of disease activity across a diverse patient cohort. Plasma proteins and autoantibodies were measured across seven SLE manifestations. Comparative analyses between pathologies and correlation with the SLE Disease Activity Index (SLEDAI) were used to identify proteins associated with organ-specific and composite disease activity. Established biomarkers of composite disease activity, SLE-associated antibodies, type I interferon (IFN), and complement C3, correlated with composite SLEDAI, but did not significantly associate with many individual SLE pathologies. Two clusters of proteins were associated with renal disease in lupus nephritis samples. One cluster included markers of infiltrating leukocytes and the second cluster included markers of tissue remodelling. In patients with discoid lupus, a distinct signature consisting of elevated immunoglobulin A autoantibodies and interleukin-23 was observed. Our findings indicate that proteins from blood samples can be used to identify protein signatures that are distinct from established SLE biomarkers and SLEDAI and could be used to conveniently monitor multiple inflammatory pathways present in different organ systems.
Asunto(s)
Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Sistémico/sangre , Nefritis Lúpica/sangre , Adulto , Autoanticuerpos/sangre , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Inflamación/sangre , Riñón/patología , Lupus Eritematoso Discoide/patología , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/patología , Masculino , Persona de Mediana EdadRESUMEN
Retinopathy in the context of systemic lupus erythematosus (SLE) is associated with severe disease and poorer prognosis. We studied retinopathy in our cohort of Indian lupus patients. Four hundred and thirty-seven patients fulfilling the Systemic Lupus International Collaborating Clinics-American College of Rheumatology-2012 criteria, attending the department of Clinical Immunology were enrolled under this cross-sectional study. A comprehensive clinical (including ophthalmological) examination and immunological profile were performed. Retinopathy was defined if cotton-wool spots, haemorrhages, vasculitis, retinal detachment or optic disc changes as papilledema, optic atrophy were present. Disease activity was assessed using SLE disease activity index (SLEDAI). Mean age of participants was 28.06 ± 9.7 years (93.1% females); median disease duration 12 months (Interquartile range-IQR 6.36). Forty-five (10.3%) had SLE associated retinopathy. Autoimmune haemolytic anaemia [31.1 vs 14.5%, p value 0.004, odd's ratio-OR (95% confidence interval-CI) 2.65 (1.33-5.29)], serositis [33.3 vs 18.9%, p value 0.023, OR (CI) 2.14 (1.11-4.10)], lupus nephritis [62.2 vs 40.8%, p value 0.006, OR (CI) 2.38 (1.26-4.50)], seizures [28.9 vs 12.8%, p value 0.004, OR (CI) 2.77 (1.36-5.65)] and median SLEDAI score (24 vs 12, p < 0.01) were significantly higher in those with retinopathy. On adjusted binary logistic regression, autoimmune hemolytic anemia, lupus nephritis and presence of antibodies to Smith antigen were predictors for retinopathy. Retinopathy is common in SLE, a marker of active disease with frequent renal involvement and should be screened for in all patients with lupus.
Asunto(s)
Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/complicaciones , Enfermedades de la Retina/etiología , Adulto , Anticuerpos Anticardiolipina/sangre , Estudios Transversales , Femenino , Humanos , India , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/sangre , Nefritis Lúpica/inmunología , Masculino , Enfermedades de la Retina/inmunologíaRESUMEN
An understanding of the differences in clinical manifestations and laboratory abnormalities between subtypes of cutaneous lupus erythematosus (CLE) is still lacking. The purpose of this study was to analyze demographic, clinical and histological features of CLE according to three main presentation subsets: acute (ACLE), subacute (SCLE) and chronic (CCLE). A 10-year retrospective analysis was performed on data from patients who were diagnosed with CLE between March 2005 and September 2015 in a Korean tertiary referral dermatology clinic. We compared demographic data and clinical and histological findings between three different CLE groups. An overall sample of 220 patients with CLE consisted of 67 patients with ACLE, 25 patients with SCLE and 135 patients with CCLE. Patients with CCLE regardless of systemic lupus erythematosus (SLE) presence had lower prevalence of anemia, urinary abnormalities and elevated erythrocyte sedimentation rate. Furthermore, CCLE patients who only had skin lesions showed lower female predominance, lower extracutaneous manifestation, fewer laboratory and immunological abnormalities including low antinuclear antibody titers and the lowest positivity for C3, C4 and anti-dsDNA, anti-Ro, anti-Sm and anti-RNP antibodies, and more prominent perieccrine inflammation and dermal fibrosis in histological findings. Considering distinct cutaneous manifestations of LE, a comprehensive awareness of each CLE subtype is important for achieving a favorable prognosis through appropriate diagnosis and management. This study provides comparative clinical and histological profiles of patients with different CLE subtypes in Korea.
Asunto(s)
Lupus Eritematoso Discoide/patología , Lupus Eritematoso Sistémico/patología , Adolescente , Adulto , Anemia/epidemiología , Anticuerpos Antinucleares/análisis , Anticuerpos Antinucleares/sangre , Sedimentación Sanguínea , Femenino , Humanos , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/epidemiología , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/inmunología , Masculino , Prevalencia , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Factores Sexuales , Piel/patología , Adulto JovenAsunto(s)
Inmunomodulación , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Discoide/inmunología , Adulto , Femenino , Humanos , Inflamación , Lupus Eritematoso Cutáneo/sangre , Lupus Eritematoso Discoide/sangre , Masculino , Microscopía Fluorescente , Persona de Mediana Edad , Linfocitos T Reguladores/citologíaRESUMEN
Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.
Asunto(s)
Anticuerpos Antinucleares/sangre , Glucocorticoides/administración & dosificación , Lupus Eritematoso Discoide , Ribonucleoproteínas/sangre , Esclerodermia Localizada , Piel/patología , Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Discoide/patología , Lupus Eritematoso Discoide/terapia , Persona de Mediana Edad , Cuello , Esclerodermia Localizada/sangre , Esclerodermia Localizada/complicaciones , Esclerodermia Localizada/patología , Esclerodermia Localizada/terapia , Síndrome , Resultado del TratamientoRESUMEN
Major gaps remain regarding pathogenetic mechanisms underlying clinical heterogeneity in lupus erythematosus (LE). As systemic changes are likely to underlie skin specific manifestation, we analyzed global gene expression in peripheral blood of a small cohort of chronic cutaneous LE (CCLE) patients and healthy individuals. Unbiased hierarchical clustering distinguished patients from controls revealing a "disease" based signature. Functional annotation of the differentially expressed genes (DEGs) highlight enrichment of interferon related immune response and apoptosis signatures, along with other key pathways. There is a 26% overlap of the blood and lesional skin transcriptional profile from a previous analysis by our group. We identified four transcriptional "hot spots" at chromosomal regions harboring statistically increased numbers of DEGs which offer prioritized potential loci for downstream fine mapping studies in the search for CCLE specific susceptibility loci. Additionally, we uncover evidence to support both shared and distinct mechanisms for cutaneous and systemic manifestations of lupus.
Asunto(s)
Perfilación de la Expresión Génica , Lupus Eritematoso Discoide/genética , Piel/patología , Adulto , Mapeo Cromosómico , Femenino , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Lupus Eritematoso Discoide/sangre , Persona de Mediana Edad , Piel/metabolismoAsunto(s)
Anticuerpos/sangre , Artritis Reumatoide/sangre , Enfermedades Pulmonares Intersticiales/sangre , Lupus Eritematoso Discoide/sangre , Péptidos Cíclicos/inmunología , Vasculitis/sangre , Enfermedad Aguda , Artritis Reumatoide/complicaciones , Humanos , Enfermedades Pulmonares Intersticiales/complicaciones , Lupus Eritematoso Discoide/complicaciones , Masculino , Persona de Mediana Edad , Vasculitis/complicacionesRESUMEN
BACKGROUND: Discoid lupus erythematosus (DLE) is a cutaneous autoimmune inflammatory disease in which the role of conventional dendritic cells (cDCs) in skin damage has not been evaluated. OBJECTIVE: To evaluate the involvement of cDCs in DLE pathogenesis. MATERIAL & METHODS: Skin biopsies from 42 patients with DLE were embedded in paraffin or placed in culture. The dermis was separated and cell suspensions were characterized by flow cytometry. RESULTS: We found an increase in cDCs with inflammatory characteristics in the skin of DLE patients, compared with control skins. Interestingly, cDCs from the DLE patients expressed low levels of the inhibitory molecule PD-L1 and showed a high expression of CCR6, which correlated with disease activity. Increased cellular death was observed in the skin of DLE patients compared with control skin and remarkably we found that damage-associated molecular patterns could be responsible for CCR6 expression on cDCs in the skin. CONCLUSIONS: Our results indicate the presence of pathogenic CCR6+ cDCs in the skin lesions of DLE patients, which could result from in situ phenotypic changes.
Asunto(s)
Células Dendríticas/metabolismo , Lupus Eritematoso Discoide/metabolismo , Lupus Eritematoso Discoide/patología , Receptores CCR6/metabolismo , Adolescente , Adulto , Anciano , Apoptosis , Antígeno B7-H1/metabolismo , Antígeno CD11c/análisis , Antígenos CD40/análisis , Recuento de Células , Movimiento Celular , Células Cultivadas , Células Dendríticas/química , Femenino , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Lupus Eritematoso Discoide/sangre , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/análisis , Receptores CCR6/análisis , Piel/química , Piel/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Adulto JovenRESUMEN
Systemic lupus erythematosus (SLE) patients with discoid lupus erythematosus (DLE) were reported to have milder disease. To test this observation, we used sandwich arrays containing 98 autoantigens to compare autoantibody profiles of SLE subjects without DLE (DLE-SLE+) (N=9), SLE subjects with DLE (DLE+SLE+) (N=10), DLE subjects without SLE (DLE+SLE-) (N=11), and healthy controls (N=11). We validated differentially expressed autoantibodies using immunoassays in DLE-SLE+ (N=18), DLE+SLE+ (N=17), DLE+SLE- (N=23), and healthy subjects (N=22). Arrays showed 15 IgG autoantibodies (10 against nuclear antigens) and 4 IgM autoantibodies that were differentially expressed (q-value<0.05). DLE-SLE+ subjects had higher IgG autoantibodies against double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), double-stranded RNA (dsRNA), histone H2A and H2B, and SS-A (52 kDa) compared with all other groups including DLE+SLE+ subjects (P<0.05). Immunoassays measuring anti-dsDNA, -ssDNA, and -SS-A (52 kDa) IgG autoantibodies showed similar trends (P<0.05). Healthy and DLE+SLE- subjects expressed higher IgM autoantibodies against alpha beta crystallin, lipopolysaccharide, heat-shock cognate 70, and desmoglein-3 compared with DLE+SLE+ and DLE-SLE+ subjects. IgG:IgM ratios of autoantibodies against nuclear antigens progressively rose from healthy to DLE-SLE+ subjects. In conclusion, lower IgG autoantibodies against nuclear antigens in DLE+SLE+ versus DLE-SLE+ subjects suggest that DLE indicates lower disease severity. Higher IgM autoantibodies against selected antigens in healthy and DLE+SLE- subjects may be nonpathogenic.
Asunto(s)
Autoanticuerpos/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Lupus Eritematoso Discoide/inmunología , Lupus Eritematoso Sistémico/inmunología , Adulto , Especificidad de Anticuerpos/inmunología , Antígenos Nucleares/sangre , Antígenos Nucleares/inmunología , Autoanticuerpos/sangre , Estudios Transversales , ADN/inmunología , ADN de Cadena Simple/inmunología , Diagnóstico Diferencial , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Técnica del Anticuerpo Fluorescente/normas , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/diagnóstico , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Proyectos Piloto , Reproducibilidad de los ResultadosRESUMEN
Discoid lupus erythematosus (DLE) is a form of local inflammatory autoimmune disease limited to the skin, involving essentially the face, scalp and ear. DLE occurs in genetically predisposed individuals, sunlight being an identified trigger. Diagnosis is made by clinical examination and histopathology; laboratory tests occasionally performed include anti-nuclear antibodies titers and presence of circulating antibodies against dsDNA. DLE patients have about a 10% chance of developing systemic lupus erythematosus (SLE), a systemic inflammatory autoimmune disease affecting a range of internal organs. Although elevated titers of anti-dsDNA antibodies is an earmark for lupus disease, they are detected in only 20-55% of DLE patients by routine laboratory tests such as enzyme-linked immunosorbent assay (ELISA). In this research, we applied an electrophoretic mobility shift assay (EMSA) in parallel with an ELISA for the detection of circulating anti-dsDNA in DLE patients. The assays were conducted on sera as well as on the immunoglobulin G fraction from sera of 24 DLE patients and of 24 healthy individuals. The EMSA was positive for all DLE patients while the ELISA was positive for only 36% of them; both assays were negative for the healthy individuals. EMSA conducted on the sera of 15 patients with lichen planus was negative in all cases. Results suggest that the EMSA is more sensitive than the routine tests used for the detection of anti-dsDNA in DLE, thus helping to improve early detection of the disease and, by extension, to better evaluate the factors triggering the disease.
Asunto(s)
Anticuerpos Antinucleares/sangre , Ensayo de Cambio de Movilidad Electroforética/métodos , Lupus Eritematoso Discoide/inmunología , Adolescente , Adulto , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/sangre , Liquen Plano/sangre , Liquen Plano/inmunología , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/diagnóstico , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: There is increased expression of type I interferon (IFN)-regulated proteins in the blood and target tissues of patients with cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). Patients with SLE have increased IFN-regulated gene expression pointing towards a possible underlying genetic defect. OBJECTIVES: To determine expression levels of five type I IFN-regulated genes that are highly expressed in SLE in the peripheral blood of patients with CLE and to correlate the expression levels with cutaneous disease activity. METHODS: Peripheral blood was obtained from 10 healthy controls and 30 patients with CLE, including eight with concomitant SLE. Total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction. Gene expression was normalized to GAPDH, standardized to healthy controls and then summed to calculate an IFN score for each patient. Disease activity was assessed with the Cutaneous Lupus Area and Severity Index (CLASI). RESULTS: Patients with subacute CLE (SCLE) and discoid lupus erythematosus (DLE) had elevated IFN scores compared with healthy controls regardless of concomitant SLE (P < 0·01 with SLE and P < 0·05 without SLE). There was no difference between patients with tumid lupus erythematosus (TLE) and healthy controls. The IFN score correlated with CLASI scores (Spearman's rho = 0·55, P = 0·0017). CONCLUSIONS: Patients with SCLE and DLE have an IFN signature, as seen in SLE. The level of gene expression correlates with cutaneous disease activity. These findings support a shared pathogenesis between SLE and some subtypes of CLE.
Asunto(s)
Interferón Tipo I/genética , Lupus Eritematoso Cutáneo/genética , Lupus Eritematoso Discoide/genética , 2',5'-Oligoadenilato Sintetasa/genética , 2',5'-Oligoadenilato Sintetasa/metabolismo , Adulto , Anciano , Antígenos de Superficie/genética , Antígenos de Superficie/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estudios de Casos y Controles , Citocinas/genética , Citocinas/metabolismo , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación de la Expresión Génica , Humanos , Interferón Tipo I/metabolismo , Lupus Eritematoso Cutáneo/sangre , Lupus Eritematoso Discoide/sangre , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Ubiquitinas/genética , Ubiquitinas/metabolismoRESUMEN
INTRODUCTION: Several studies have reported that TNFα is substantially increased within skin lesions of patients with discoid lupus erythematosus (DLE), subacute cutaneous lupus erythematosus (SCLE) and dermatomyositis (DM) compared to controls. Elevated TNFα has been reported in the sera of some patients with systemic lupus erythematosus, DLE and SCLE, but not in the sera of patients with DM. Because of the key pathogenic role of autoimmunity in these diseases, in this study we sought to evaluate TNFα production by a readily available source of immune cells (namely, peripheral blood mononuclear cells (PBMCs)) taken from controls and from patients with cutaneous lupus or DM. METHODS: Freshly isolated PBMCs were cultured overnight, and TNFα protein accumulation in conditioned medium was determined. In addition, flow cytometry using cell-type-specific markers was performed to determine the sources of TNFα. One-way analysis of variance and Dunnett's multiple comparisons test were performed for statistical comparisons. RESULTS: Accumulation of TNFα protein in conditioned medium containing PBMCs from DLE patients, but not from SCLE, TLE or DM patients, was significantly greater (19-fold) than that from controls (P < 0.001). In DLE PBMCs, increased TNFα was produced by circulating monocytes and myeloid dendritic cells (mDCs). The mean TNFα fluorescence intensity, but not the total number, of both monocytes and mDCs (P < 0.01) from DLE patients was significantly greater (2.3-fold) than that of controls. There were significantly more (13.3-fold) mDCs with intracellular TNFα in blood from DLE patients (P < 0.001) and DM patients (P < 0.001) compared to controls. Most importantly, a positive correlation was seen in DLE patients between their disease activity measured using the Cutaneous Lupus Erythematosus Disease Area and Severity Index and TNFα protein secretion (r = 0.61, P < 0.08). CONCLUSIONS: TNFα protein production by PBMCs is greater in DLE patients than in patients with other cutaneous forms of lupus and DM or in controls. Flow cytometric studies demonstrated that circulating monocytes and mDCs contributed to this increased TNFα production. Monocytes and mDCs are present in lesional skin, and the increased TNFα production by these cells and other PBMCs likely increase the number of inflammatory cells seen in DLE skin relative to other subsets of cutaneous lupus erythematosus and DM. These results provide a possible biological explanation for the denser infiltrate seen in DLE relative to DM.
Asunto(s)
Dermatomiositis/sangre , Leucocitos Mononucleares/metabolismo , Lupus Eritematoso Cutáneo/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Análisis de Varianza , Células Cultivadas , Dermatomiositis/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Lupus Eritematoso Cutáneo/patología , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/patología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Cutaneous lupus erythematosus (CLE) is characterized by enhanced interferon α (IFNα) levels in serum and in tissue. Since IFNα promotes a Th1-biased immune response, we hypothesized that a Th1-associated chemokine receptor profile should be a typical finding in patients with active CLE. Therefore, peripheral blood mononuclear cells were isolated from patients with different CLE subsets (n = 15), healthy controls (n = 13) and patients under immunotherapy with IFNα (n = 7). T helper cells were analysed by flow cytometry for the expression of the chemokines receptor CCR5, indicative for Th1 cells, and of CCR3, indicating Th2. In addition, intracellular levels of the type I IFN-inducible MxA protein were measured. Patients with widespread active CLE skin lesions had a significantly increased expression of CCR5, whereas expression of CCR3 was decreased when compared with healthy controls. MxA expression was significantly enhanced in all investigated CLE subtypes, with the highest levels in patients with widespread skin lesions. The enhanced CCR5/CCR3 ratio closely correlated with the MxA levels in peripheral lymphocytes and with disease activity. Our analyses revealed that active CLE is associated with a systemic type I IFN effect that appears to induce a shift towards a Th1-associated chemokine receptor profile. The CCR5/CCR3 T-helper cell ratio might therefore represent an indirect marker for the disease activity in CLE.
Asunto(s)
Lupus Eritematoso Cutáneo/inmunología , Células TH1/inmunología , Células Th2/inmunología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Proteínas de Unión al GTP/sangre , Humanos , Interferón-alfa/uso terapéutico , Lupus Eritematoso Cutáneo/sangre , Lupus Eritematoso Cutáneo/tratamiento farmacológico , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/inmunología , Masculino , Persona de Mediana Edad , Proteínas de Resistencia a Mixovirus , Receptores CCR3/sangre , Receptores CCR5/sangre , Células TH1/metabolismo , Células Th2/metabolismo , Adulto JovenRESUMEN
T-lymphocytes are believed to play an important role in the pathogenesis of discoid lupus erythematosus (DLE). However, the reasons that lead to loss of tolerance and to development of autoimmunity in DLE remain unclear. In the present paper, we investigated serum levels of the regulatory cytokines transforming growth factor (TGF)-ß and interleukin (IL)-10 in 25 newly diagnosed patients with DLE, 15 with systemic lupus erythematosus (SLE), 10 with psoriasis, 10 with atopic dermatitis (AD) and 20 healthy controls (HC). TGF-ß serum levels were significantly lower in patients with DLE compared with patients with psoriasis and HC, while no differences were found between DLE, SLE and AD (medians: DLE: 28.49 ng/ml; psoriasis: 42.77 ng/ml; HC: 43.71 ng/ml; DLE vs. psoriasis: p < 0.05; DLE vs. HC: p < 0.05). IL-10 concentrations were reduced in DLE serum samples with respect to SLE, psoriasis, AD and HC (medians: DLE: 46.42 pg/ml; SLE: 127.64 pg/ml; psoriasis: 109.3 pg/ml; AD: 76.3 pg/ml; HC: 114.71 pg/ml; DLE vs. SLE: p < 0.05; DLE vs. psoriasis: p < 0.05; DLE vs. AD: p < 0.05; DLE vs. HC: p < 0.05). The downregulation of TGF-ß and IL-10 in DLE may lead to defective immune suppression and thus to the generation of the tissue injury that is found in lupus patients.
Asunto(s)
Interleucina-10/sangre , Lupus Eritematoso Discoide/inmunología , Factor de Crecimiento Transformador beta/sangre , Adulto , Estudios de Casos y Controles , Dermatitis Atópica/sangre , Dermatitis Atópica/inmunología , Regulación hacia Abajo , Femenino , Humanos , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Psoriasis/sangre , Psoriasis/inmunologíaRESUMEN
Annexin 1 is an anti-inflammatory molecule and has also been described to be a common target of autoantibodies. In this study, we determined whether antibodies against annexin 1 can be detected in sera of patients with cutaneous lupus erythematosus (CLE). Levels of anti-annexin 1 antibodies were evaluated by a new established enzyme-linked immunosorbent assay and found to be significantly higher in sera of patients with CLE when compared to normal healthy donors (NHD). Moreover, the percentage of sera positively tested for anti-annexin 1 antibodies was elevated in patients with CLE when compared to NHD. In particular, the percentage of positive sera for anti-annexin 1 antibodies was significantly higher in patients with discoid lupus erythematosus (DLE); however, disease activity did not correlate with the antibody levels. The results of this study indicate that anti-annexin 1 antibodies in sera of patients with DLE might be a valuable aid in the diagnosis of this subtype.
Asunto(s)
Anexina A1/sangre , Autoanticuerpos/sangre , Biomarcadores/sangre , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Pancreatitis complicating a diagnosis of systemic lupus erythematosus (SLE) is rarely reported in the literature and there are no known published cases thus far in the Caribbean. A 50-year old female diagnosed with SLE and discoid lupus erythematosus (DLE) since 1990, presented in February, 2009, to the University Hospital of the West Indies (UHWI), Kingston, Jamaica, with symptoms suggestive of lupus pancreatitis. Serum amylase level was 2341 IU/L and serum lipase was 203 IU/L. Pancreatitis has a 3-8% rate of occurrence in adult patients with SLE. Aetiology and management of this entity remains controversial in these cases, but one must bear the diagnosis in mind, when faced with a SLE patient presenting with abdominal pain, vomiting and diarrhoea.
La pancreatitis que complica el diagnóstico del lupus eritematoso sistémico (LES), raramente se reporta en la literatura, y hasta hoy no se conoce de caso alguno publicado en el Caribe. Una mujer de 50 años de edad, a quien se le diagnosticara lupus eritematoso sistémico (LES), y lupus eritematoso discoide (LED) desde 1990, acudió en febrero de 2009 al Hospital Universitario de West Indies, Kingston, Jamaica, con síntomas que sugerían una pancreatitis por lupus. El nivel de amilasa sérica fue 2341 IU/L y el de lipasa sérica fue 203 IU/L. La pancreatitis tiene una tasa de ocurrencia de 3-8% en pacientes adultos con LES. La etiología y el tratamiento de esta entidad siguen siendo controversiales en estos casos, pero se debe tener presente el diagnóstico frente a pacientes de SLE que presenten dolor abdominal, vómito y diarrea.
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Pancreatitis/etiología , Amilasas/sangre , Jamaica , Lipasa/sangre , Lupus Eritematoso Discoide/sangre , Lupus Eritematoso Discoide/complicaciones , Lupus Eritematoso Sistémico/sangre , Pancreatitis/sangreRESUMEN
BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression. MATERIAL AND METHODS: 89 subjects were recruited and divided in 5 groups-10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry. RESULTS: Immunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p<0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p<0.05). Serum IL-17A levels were similar in SCLE and negative controls (p>0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p<0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p>0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p<0.05). CONCLUSION: IL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.