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1.
Lupus ; 17(4): 337-47, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18413417

RESUMO

Our objective was to characterize clinical features, laboratory findings, concomitant autoimmune diseases, and smoking habits of lupus erythematosus subgroups in genetically homogeneous patients from two Dermatology Departments of Finnish University hospitals. One hundred and seventy eight discoid lupus erythematosus, 55 subacute cutaneous lupus erythematosus, and 77 systemic lupus erythematosus patients were enrolled using patients' charts from institutional database (1995-2006) and during routine control visits. Clustering analysis was performed to reveal natural groupings. Smoking at the onset of disease was significantly more common in all subgroups (57% for discoid lupus erythematosus, 35% for subacute cutaneous lupus erythematosus, and 34% for systemic lupus erythematosus) compared with the age/gender-matched prevalence in the Finnish population, suggesting smoking to be a trigger factor for cutaneous lupus. Leukopenia (38%) and lymphopenia (52%) were observed more often in patients with systemic lupus erythematosus than reported previously. Photosensitivity characterized all groups, especially patients with subacute cutaneous lupus erythematosus (87%). Of the autoimmune diseases, Sjögren's syndrome was the most common (22% of patients with systemic lupus erythematosus), followed by autoimmune thyroid disease (13% of patients with subacute cutaneous lupus erythematosus). The clustering analysis showed environmental factors (smoking) to be more involved in disease development in discoid lupus erythematosus, whereas immunological factors were more significant in initiating systemic lupus erythematosus. The high prevalence of autoimmune thyroid disease, together with photosensitivity, and the clustering profiles suggest that lupus erythematosus subtypes, especially discoid lupus erythematosus, are heterogeneic in their pathomechanisms.


Assuntos
Lúpus Eritematoso Cutâneo/diagnóstico , Pele/patologia , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Lúpus Eritematoso Cutâneo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Br J Dermatol ; 157(5): 970-80, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17854363

RESUMO

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to tissue destruction, regeneration, inflammation and apoptosis and several of them are upregulated by ultraviolet (UV) radiation in skin. Although some MMPs associate with organ manifestations of systemic lupus erythematosus (SLE), their role in cutaneous lupus erythematosus (LE) is elusive. OBJECTIVES: Our aim was to evaluate the expression of MMPs in SLE, subacute cutaneous LE (SCLE) and discoid LE (DLE) skin lesions and their relation to apoptosis and epidermal changes. METHODS: Lesional skin biopsies from 20 patients with SLE, 20 with DLE and 17 with SCLE, and from UVA/UVB-photoprovoked skin of healthy volunteers were immunostained using antibodies to multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs). The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling) method was used for detection of apoptosis. RESULTS: MMP-3, -10, -19 and -26 were abundantly expressed by keratinocytes in SLE, DLE and SCLE skin samples. MMP-7 was detected in keratinocytes in regions of oedema and vacuolization especially in SLE and SCLE, while MMP-14 was only occasionally observed in keratinocytes. Photoprovocation did not induce MMP-10 or -26 expression in skin of healthy volunteers. Epithelial TIMP-1 expression was low while occasional positive fibroblasts were seen in the dermis. TIMP-3 was abundantly expressed in the epidermis, endothelial cells and macrophages. CONCLUSIONS: Different subtypes of cutaneous LE are fairly similar in their MMP expression profile. MMP-3 and -10 mediate both epidermal changes and dermal tissue remodelling but are not present in lymphocytes. Low expression of TIMP-1 suggests that lupus skin is characterized by proteolytic events, and targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues.


Assuntos
Lúpus Eritematoso Cutâneo/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Estudos de Casos e Controles , Epiderme/metabolismo , Feminino , Humanos , Marcação In Situ das Extremidades Cortadas , Queratinócitos/metabolismo , Lúpus Eritematoso Discoide/metabolismo , Masculino , Pessoa de Meia-Idade
3.
Scand J Rheumatol ; 33(4): 246-52, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15370721

RESUMO

OBJECTIVE: To determine the prevalence of antibodies to phospholipid-binding plasma proteins (aPL) and to oxidized low-density lipoprotein (OX-LDL), and to study the association of these antibodies with thrombosis and coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE). METHODS: Clinical data and sera from 89 Finnish patients with familial and 203 with sporadic SLE were available for the study. Enzyme-linked immunosorbent assays (ELISA) were used for antibody determination. RESULTS: The occurrence of thrombosis in our SLE patients was 13.7% (40/292) and of clinically diagnosed CHD was 1.4% (4/292). All antibody assays, except IgM-aCL, were significantly associated with thrombosis. IgG-aCL alone or in combination with anti beta 2-GPI or with anti OX-LDL were reasonably sensitive (38%, 48%, and 58%, respectively) and specific (87%, 80% and 72%, respectively) for a history of thrombosis. A high risk of arterial thrombosis (TIA or stroke) was associated with positivity of IgG-aCL, anti beta 2-GPI, and anti-prothrombin. Venous thrombosis was significantly associated with all other assays except IgM-aCL and anti-prothrombin. No test correlated with CHD, but the number of affected patients was small. There were three multiplex SLE families with two patients having a history of thrombosis: no consistent pattern of aPL or anti OX-LDL was found in these patients. CONCLUSION: IgG-aCL alone or in combination with anti beta 2-GPI or anti OX-LDL are sensitive and specific tests for detecting SLE patients at increased risk of thrombosis. The aetiopathogenesis of thrombosis in familial SLE appears to be multifactorial.


Assuntos
Anticoagulantes/imunologia , Cardiolipinas/imunologia , Glicoproteínas/imunologia , Imunoglobulina G/análise , Imunoglobulina M/análise , Lipoproteínas LDL/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Protrombina/imunologia , Trombose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/análise , Cardiolipinas/análise , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Finlândia , Glicoproteínas/análise , Humanos , Lipoproteínas LDL/análise , Masculino , Pessoa de Meia-Idade , Oxirredução , Valor Preditivo dos Testes , Protrombina/análise , Fatores de Risco , Sensibilidade e Especificidade , beta 2-Glicoproteína I
4.
Ann Rheum Dis ; 63(10): 1250-4, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15361381

RESUMO

OBJECTIVE: To investigate the prevalence and diagnostic significance of antibodies against telomeric DNA in systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases, and to make comparisons with five conventional anti-DNA or anti-nuclear antibody (ANA) assays. METHODS: Antibodies to telomeres, which are highly repetitive sequences of DNA (TTAGGG/CCCTAA) at the end of eukaryotic chromosomes, were measured by an enzyme linked immunosorbent assay (ELISA) in 305 patients with SLE and 125 patients with other autoimmune rheumatic diseases (78 rheumatoid arthritis, 32 primary Sjögren's syndrome, eight mixed connective tissue disease, seven miscellaneous rheumatic diseases). Other assays used were two commercial ELISA assays for anti-dsDNA using calf thymus as antigen, Crithidialuciliae immunofluorescence, and radioimmunoassay (RIA) for anti-dsDNA and immunofluorescence using Hep-2 cells for ANA. RESULTS: The prevalence of anti-telomere in SLE was 60%, v 5% in rheumatoid arthritis and 18% in other autoimmune rheumatic diseases. Specificity of anti-telomere for SLE was 91%; positive and negative predictive values were 95% and 46%, respectively. For anti-dsDNA by two ELISA assays using calf thymus as antigen, sensitivities were 69% and 29% and specificities 66% and 96%, respectively. Other anti-dsDNA assays had low sensitivities (RIA 43%, Crithidia immunofluorescence 13%). The association of anti-telomere with a history of nephritis in patients with SLE was stronger (p = 0.005) than by any other assay (p = 0.006-0.999). The correlations between the different assays were good (p<0.001 for all comparisons). CONCLUSIONS: The new ELISA for anti-telomere antibodies using standardised human dsDNA as antigen is a sensitive and highly specific test for SLE.


Assuntos
Anticorpos Antinucleares/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Telômero/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Biomarcadores/sangue , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/imunologia , Sensibilidade e Especificidade
6.
J Rheumatol ; 28(4): 758-60, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11327246

RESUMO

OBJECTIVE: To perform a cross sectional nation-wide clinical study of familial systemic lupus erythematosus (SLE) in Finland. METHODS: We sought to identify all Finnish families in which at least 2 members satisfied the classification criteria for SLE. About 1,200 patients with SLE (80-85% of all patients attending Finnish hospitals) were contacted. Personal and/or phone interviews and examination of medical records were used to verify the diagnoses. A comparison of clinical characteristics was made between familial cases of SLE and matched sporadic controls. RESULTS: We identified 53 multiplex families with 113 SLE patients. Forty-six families had 2 affected members and 7 families had 3 affected members. There were 3 pairs of monozygotic female twins and one pair of dizygotic twins of the opposite sex concordant for SLE. Eleven (9.7%) of the 113 familial cases of SLE were male. No differences were found in the clinical presentation of SLE between familial and sporadic cases (sex, age at onset, major clinical manifestations, and common laboratory tests). The incidence of familial SLE was approximately 4-5%. CONCLUSION: Our study shows that familial and sporadic SLE are not different disease entities; this means that we can extrapolate the results of future genetic analyses in multiplex SLE families to all patients with SLE.


Assuntos
Lúpus Eritematoso Sistêmico/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doenças em Gêmeos , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Lactente , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Gêmeos Dizigóticos , Gêmeos Monozigóticos
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