RESUMEN
With a cross sectional study of 465 consecutive systemic lupus erythematosus (SLE) patients tested for 13 autoantibodies (Aab) and two idiotypes we determined the prevalence of Aab according to disease activity, both general and at particular organ systems. Seventy seven percent of SLE sera had at least one Aab and 56% had it at high titres. Pathogenic idiotypes had a prevalence of less than 10% and 166 sera had Aab to 5 or more antigens and 9 sera had Aab against all 13 antigens tested. Patients with active disease had increased prevalence of Aab to DNP, ssDNA, ENA, mitochondria and histones when considered at 5 s.d. above the mean of normal controls. The higher positivity of Aab in patients with active disease was confirmed in logistic regression analysis adjusted by age, disease duration, and intensity of treatment. A trend was observed of increased prevalence and titres of Aab from inactive disease without treatment, to inactive disease but still being treated, to active disease. Only 22% of patients with active disease had no Aab and the higher the number of Aab the higher the frequency of active disease. Patients with active arthritis, and to a lesser degree those with active mucocutaneous involvement, had higher prevalence and titres of most autoantibodies than patients with disease activity at other organ systems. Active renal disease associated only with anti-dsDNA, whereas active CNS disease associated with anti-mitochondrial Aab. Our findings support the vision of SLE as an immune dysregulation leading to polyclonal B cell activation with resulting production of multiple Aab. Their profiles seem influenced by genetical, hormonal and environmental factors and, in turn, they contribute to the clinical picture in each patient. Disease activity influences the presence of some, but not all, Aab and some of them may remain present in some patients, even in remission.
Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Idiotipos de Inmunoglobulinas/sangre , Lupus Eritematoso Sistémico/inmunología , ARN Citoplasmático Pequeño , Adulto , Anticuerpos Anticardiolipina/sangre , Anticuerpos Anticardiolipina/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Especificidad de Anticuerpos , Autoantígenos/inmunología , Enfermedades Autoinmunes/sangre , Estudios Transversales , ADN/inmunología , ADN de Cadena Simple/inmunología , Femenino , Histonas/inmunología , Humanos , Lupus Eritematoso Sistémico/sangre , Masculino , México/epidemiología , Persona de Mediana Edad , Mitocondrias/inmunología , ARN de Transferencia/inmunología , Ribonucleoproteínas/inmunología , Ribonucleoproteínas Nucleares Pequeñas/inmunología , Índice de Severidad de la Enfermedad , Antígeno SS-BRESUMEN
Primary Sjögren's syndrome (PSS) is an autoimmune inflammatory disorder characterized by lymphocytic infiltration of exocrine glands, B cell hyperactivity and autoantibody production. The aim of this study was to determine the presence of IL-10 and IL-13 in this disease. We studied the IL-10 and IL-13 gene expression in vivo by peripheral blood mononuclear cells and minor salivary glands from PSS patients. We found a high expression of the IL-10 gene and its product by their peripheral blood mononuclear cells (PBMC) as well as by their salivary glands. Peripheral blood B cells and monocytes were responsible for 89% of total IL-10 secretion. IL-13 gene expression was not observed in PBMNC from either PSS patients or healthy controls, and was confined to PSS salivary glands. Our results suggest that IL-10 and IL-13 contribute to the pathogenesis of PSS and might explain the B cell abnormalities and the development of lymphoma observed in this autoimmune disease.
Asunto(s)
Regulación de la Expresión Génica/inmunología , Interleucina-10/biosíntesis , Interleucina-13/biosíntesis , Leucocitos Mononucleares/metabolismo , Glándulas Salivales/metabolismo , Síndrome de Sjögren/inmunología , Femenino , Humanos , Interleucina-10/genética , Interleucina-13/genética , Leucocitos Mononucleares/inmunología , Masculino , ARN Mensajero/análisis , Glándulas Salivales/inmunología , Síndrome de Sjögren/metabolismoRESUMEN
We studied mononuclear cell subsets in 17 patients with primary Sjögren's syndrome (PSS) and in 11 normal controls by flow cytometry. We found a decreased percentage of CD4+ cells (p = 0.027) and a higher percentage of CD8+ cells in patients as compared to controls. In both, CD4+ cells and CD8+ cells, CD25 antigen was overexpressed (p = 0.005 and p = 0.025, respectively as compared to controls). We then measured spontaneous mRNA cytokine expression by T cells from 7 PSS patients and 5 normal controls by coupled reverse transcription-polymerase chain reaction. We found spontaneous mRNA expression for IFN-gamma, IL-10, IL-13 as well as for CD25. Our results suggest an overall T cell activation in PSS patients and provides evidence of a T cell cytokine regulatory imbalance which may play a role in the pathogenesis of this disease.
Asunto(s)
Citocinas/genética , Receptores de Interleucina-2/análisis , Síndrome de Sjögren/inmunología , Linfocitos T/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Humanos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , ARN Mensajero/análisisRESUMEN
The pattern of inheritance of autoantibodies in eight families chosen from a pool of 110 families of patients with systemic lupus erythematosus (SLE) is described. In all the eight families at least two members were already affected by SLE. In total, 19 patients and 43 first degree relatives were examined. The inheritance of a large set of antinuclear antibodies (for example, DNA, Sm, RNP, Ro, La, histones) and 16/6 idiotype seemed to be related to some unknown genetic factors but not related to HLA. The presence of numerous antinuclear autoantibodies in the serum of a subject was not necessarily associated with overt disease. The incidence of the 16/6 idiotype among patients and their relatives was low. It is not yet clear whether the 'autoantibody burden' is greater in families with multiple cases of SLE than in families with single cases.
Asunto(s)
Autoanticuerpos/genética , Lupus Eritematoso Sistémico/genética , Diversidad de Anticuerpos , Susceptibilidad a Enfermedades , Familia , Femenino , Antígenos HLA/genética , Humanos , Lupus Eritematoso Sistémico/inmunología , Masculino , LinajeRESUMEN
Patients with primary antiphospholipid syndrome (PAPS) have few or no autoantibodies, other than the antiphospholipid antibodies (aPL) that could be natural autoantibodies encoded by germline genes. Some of the autoantibodies marked by the human anti-DNA common idiotype 16/6 have been found to be encoded by unmutated germline genes. Hence, we tested the sera of 19 patients with PAPS for the presence of the 16/6 idiotype which has also been found to be expressed on antibodies that bind cardiolipin. For this we used an ELISA method with antiserum against the SA1 idiotype which recognizes the 16/6. Five of our patients had the idiotype in at least one serum. Among the patients there was one with a variant of PAPS with hemolytic anemia and an IgM antibody to phosphatidylcholine that is akin to the natural autoantibody of normal mice encoded by germline genes VH11 and VH12. Inhibition studies with ssDNA, dsDNA and cardiolipin revealed that all 3 antigens decreased the serum levels of the SA1 idiotype despite absence of detectable anti-DNA antibodies by other methods. Our findings suggest that within the B cell clones that produce aPL in patients with PAPS there are some that produce immunoglobulins bearing 16/6 related idiotypes. This could indicate that some of the aPL present in patients with PAPS derive from natural autoantibody producing cell clones.