RESUMEN
BACKGROUND: Lupus erythematosus (LE) is an autoimmune disease characterized by a heterogeneous spectrum of skin manifestations and organ affection, and is frequently associated with serum autoantibodies, which mostly remain positive through the course of the disease. The classification of LE is still a controversial topic. OBJECTIVES: To examine the prevalence and long-term course of autoantibodies in patients with cutaneous LE (CLE) and/or systemic LE (SLE) treated in the outpatient clinic for connective tissue diseases of the department of Dermatology in Bochum, Germany. METHODS: Four hundred and two patients with LE were evaluated for antinuclear antibodies at a whole of 1572 time points. The prevalence as well as the long-term positivity of antinuclear antibodies and their correlation with the various subtypes of disease was examined. RESULTS: Antinuclear antibody (ANA) testing and anti-ds-DNA antibodies were not only more prevalent in SLE patients (as expected from the ACR criteria for diagnosis of SLE, P < 0.0001), but also have had a more consistent course in the long-term evaluation (P = 0.0001 and P = 0.0111 respectively). Subacute cutaneous LE (SCLE) was associated with ANA (P = 0.0075), anti-Ro (P < 0.0001) and anti-La (P < 0.0001) antibodies, showing also higher consistency rates for these antibodies than discoid LE (DLE, P = 0.049, P = 0.004, P = 0.0004). Our data from 100 patients with LE tumidus (LET) support its perception as a distinct subtype of LE, not correlating with systemic disease or antinuclear antibodies (P < 0.0001). Anti-U1-ribonucleoprotein antibodies correlated with CLE in SLE patients (P = 0.0237), whereas non-LE-specific antinuclear antibodies were a rare, inconsistent autoimmune epiphenomenon in patients with SLE. CONCLUSION: Long-term analysis of antinuclear antibodies has shown significant differences in various clinical subtypes of LE, confirming the actual classification of the disease. A serial evaluation of antinuclear antibodies may support the classification of disease in LE patients with overlapping clinical features.
Asunto(s)
Anticuerpos Antinucleares/inmunología , Lupus Eritematoso Cutáneo/inmunología , HumanosRESUMEN
BACKGROUND: Lupus erythematosus (LE) is an autoimmune disease in which regulatory T cells play a pathogenetic role. OBJECTIVES: We aimed to assess and compare the quantities of lesional Tregs in subtypes of cutaneous LE (CLE) including chronic discoid LE (CDLE), LE tumidus (LET) and subacute CLE (SCLE). METHODS: Thirty-nine patients with CLE were enrolled in the study. Immunohistochemistry was performed for CD4, CD8, FOXP3 and CD39. RESULTS: We studied nine CDLE patients, 21 LET patients and nine patients with SCLE. SCLE lesions [37 (0-134)] showed a significantly (P = 0.024) decreased percentage of CD4+ cells when compared with CDLE [125 (0-146)] and LET [124 (0-240)] lesions. Moreover, the CD4/CD8 ratio in SCLE lesions [0.7 (0.5-1.8)] was significantly (P = 0.027) decreased when compared with CDLE [1.9 (1.5-2.8)] and LET [1.6 (0.8-2.9)] lesions. FOXP3 immunopositivity was significantly (P = 0.017) decreased in LET [0 (0-6)] and SCLE [1 (0-2)] lesions when compared with CDLE [6 (0-38)]. Moreover, in LET [2 (0-6)] and SCLE [2 (0-2)], we observed a significantly (P = 0.0049) diminished CD39-immunoreactivity when compared with CDLE [4 (2-12)]. CD4+ cell count is a significant (P = 0.0133) negative predictor for the diagnosis of SCLE (Odds ratio 0.978, 95% CI 0.960-0.99). CONCLUSIONS: Our data indicate that there are differences in quantities of lesional T helper cells, CD4/CD8 ratio and Tregs among subtypes of CLE. Interestingly, a more significant decrease in Tregs, which likely reflects greater loss of immune-tolerance, is observed in the more photosensitive subtypes of CLE such as SCLE and LET.
Asunto(s)
Antígenos CD , Apirasa , Relación CD4-CD8 , Factores de Transcripción Forkhead , Lupus Eritematoso Cutáneo/inmunología , Linfocitos T Reguladores/química , Adulto , Anciano , Antígenos CD4/análisis , Antígenos CD8/análisis , Femenino , Humanos , Inmunidad Celular , Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Discoide/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Glutathione S-transferases (GSTs) are involved in detoxification of xenobiotics such as fumaric acid esters (FAE). OBJECTIVES: To perform GSTT1 geno- and phenotyping in psoriasis patients treated with FAE to find out whether the responder status and/or occurrence of side-effects are associated with allelic variants and enzymatic activity of GSTT1. METHODS: We treated 106 psoriasis patients with FAE. GSTT1 genotyping was performed using PCR, phenotyping was carried out by means of a validated high performance liquid chromatography assay at baseline and under treatment. RESULTS: The distribution of GSTT1 genotypes was as follows: 31% *A/*A; 49% *A/*0; 20% *0/*0. GSTT1 phenotypes as expressed in enzyme activity significantly differed between conjugators classes. (P < 0.001). GSTT1 activity under treatment was significantly (P = 0.0001) increased when compared with baseline. There were no significant associations between the aforementioned GSTT1 pheno- and genotypes and clinical parameters such as psoriasis area and severity index (PASI)50, adverse effects and FAE dosage (P > 0.05), except for the frequent occurrence of reduction (>50%) of circulating lymphocytes in patients with *0/*0 GSTT1 status (P = 0.036; odds ratio: 6, 95% CI: 1.1-32). CONCLUSION: GSTT1 geno- and phenotypes significantly correlate in psoriasis patients and do not substantially differ from healthy controls. Response to FAE does likely not depend on GSTT1. However, *0/*0 GSTT1 status is a predictor for the occurrence of marked reduction of lymphocyte counts under FAE therapy. Notably, FAE seem to enhance GSTT1 enzyme activity in high and low conjugators.