RESUMEN
Plasma concentration of TNF-alpha and its type I receptor (p55TNF-R) was examined in 126 patients with drug-induced skin reactions using immunoenzymatic ELISA method. Patients were subdivided into 6 groups: maculopapular eruptions (ME), erythema multiforme (EM), erythema multiforme coexisting with erythema nodosum (EMN), hyperergic vasculitis (HV), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). In the acute clinical stage highly significant (p<0.001) or significant (p<0.01) elevation of mean plasma concentrations of the cytokine and its receptor was found in all examined groups in comparison with the control. Clearing of clinical symptoms was connected with considerable decrease (p<0.001, p<0.01) of mean plasma levels of the both proteins in comparison with the before treatment values. TNF-alpha concentrations still remained significantly more elevated than those observed in the control. The results indicate that plasma activity of TNF-alpha and its p55 receptor change with the clinical course of the examined drug-induced skin reactions, which suggests the partake of both proteins in the pathogenesis of these diseases.
Asunto(s)
Erupciones por Medicamentos/sangre , Inmunoglobulina G/sangre , Receptores del Factor de Necrosis Tumoral/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Eritema/sangre , Eritema/inducido químicamente , Etanercept , Femenino , Humanos , Inmunosupresores/sangre , Masculino , Persona de Mediana Edad , Parapsoriasis/sangre , Parapsoriasis/inducido químicamente , Síndrome de Stevens-Johnson/sangre , Síndrome de Stevens-Johnson/inducido químicamente , Síndrome de Stevens-Johnson/etiología , Factores de Tiempo , Urticaria/sangre , Urticaria/inducido químicamente , Vasculitis/sangre , Vasculitis/inducido químicamenteRESUMEN
Cutaneous T cell lymphoma (CTCL) and reactive T cell skin diseases represent opposite ends of a spectrum of diseases ranging from overtly malignant to persistently benign. Within this spectrum, the parapsoriasis group is not clearly defined regarding malignant potential. In contrast to consistent findings in advanced-stage CTCL, clonality analysis of parapsoriasis has produced conflicting results in previous studies. As T cell receptor gamma-chain polymerase chain reaction GeneScan analysis (TCR-gamma-PCR-GSA) stands out by its sensitivity, its accuracy in size determination of PCR products, its capacity to identify false positives by repeated analysis and its easy applicability, this approach was used to analyse the clonality status of 41 patients with borderline T cell lymphoproliferative skin diseases, including parapsoriasis (n=27) and early-stage mycosis fungoides (MF) (n=14). A monoclonal T cell infiltrate was demonstrated by repeated TCR-gamma-PCR-GSA in lesional skin specimens in 19.2% of parapsoriasis patients and in 66.6% of early-stage MF cases (p=0.013). In peripheral blood, a monoclonal T cell population was found in a similar percentage of parapsoriasis and of early-stage MF patients (26.7% versus 12.5%; p=0.611). A detailed analysis of parapsoriasis subentities, namely small and large plaque parapsoriasis, and parapsoriasis lichenoides, revealed monoclonality in 2(6)/2(5), 3(14)/2(8) and 0(6)/0/(3) of the skin and peripheral blood specimens, respectively. The high detection rate of false positive cases by repeated analysis (20-37.5%) provides a corrected perspective for the high rates of dominant T cell clones found by others in the peripheral blood of such patients. From the results obtained, three major conclusions can be drawn: firstly, CTCL is clearly associated with detection of monoclonality, even in its early stages; secondly, monoclonality is not a prerequisite for potential CTCL precursor entities; and thirdly, recirculating malignant T cells identical to the skin clone are not readily detected in parapsoriasis or early-stage MF, but may rather indicate disease progression.
Asunto(s)
Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Micosis Fungoide/genética , Parapsoriasis/genética , Piel/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Células Clonales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/sangre , Parapsoriasis/sangre , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunologíaRESUMEN
We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.
Asunto(s)
Linfocitos T CD4-Positivos/enzimología , Micosis Fungoide/sangre , Parapsoriasis/sangre , Subgrupos de Linfocitos T/fisiología , Telomerasa/metabolismo , Telómero/genética , Anciano , Anciano de 80 o más Años , Antígenos de Diferenciación de Linfocitos T , Antígenos de Neoplasias , Linfocitos B/fisiología , Southern Blotting , Complejo CD3/análisis , Linfocitos T CD8-positivos/fisiología , Femenino , Humanos , Masculino , Glicoproteínas de Membrana/análisis , Persona de Mediana Edad , Micosis Fungoide/enzimología , Micosis Fungoide/genética , Micosis Fungoide/inmunología , Parapsoriasis/enzimología , Parapsoriasis/genética , Valores de Referencia , Mapeo Restrictivo , Linfocitos T/inmunología , Linfocitos T/fisiologíaRESUMEN
T-cell receptor gene rearrangement analysis is a useful technique to detect clonality and determine lineage of lymphoid neoplasms. We examined 103 patients with mycosis fungoides, Sézary syndrome, peripheral T cell lymphoma, potentially malignant lymphoproliferative disorders including pre-Sézary syndrome, large plaque parapsoriasis, lymphomatoid papulosis and follicular mucinosis, and various benign inflammatory infiltrates. A clonal rearrangement was detected in skin samples in 20 of 24 patients with mycosis fungoides and in peripheral blood samples in 19 of 21 patients with Sézary syndrome. A clonal population was also detected in seven of eight cases classified as peripheral T cell lymphoma. The potentially malignant dermatoses tended to have clonal rearrangement, with the exception of large plaque parapsoriasis, and further follow-up is needed to correlate clonality with the disease course. These studies demonstrate the value of molecular genetics as an adjunct to morphology in the examination of patients with cutaneous lymphoproliferative disease.