José Ordi-Ros

Libman-Sacks endocarditis in the antiphospholipid syndrome: immunopathologic findings in deformed heart valves:

Objective. To examine the potential immunologic mechanism and involvement of antiphos pholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphos pholipid syndrome (APS). Methods. Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immuno globulins, complement components, serum albumin and a monoclonal anti-idiotypic anti body to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls. Results. Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS. Conclusion. Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.

DNase 1 activity in patients with systemic lupus erythematosus: relationship with epidemiological, clinical, immunological and therapeutical features

The main objective of this study is to determine the relationship between the activity of DNase1 and the clinical and immunological features in patients with systemic lupus erythematosus (SLE). A total of 66 patients (8 men and 58 women) diagnosed with SLE according to the American College of Rheumatology (ACR) SLE classification criteria were included in the study. Sixty-two sera from healthy blood donors were also included as controls. Epidemiological, clinical, immunological and therapeutical features for each patient were obtained. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). DNase1 activity was determined by using a radial enzyme diffusion method. Statistical analysis was performed using SPSS 12.0 software, with significant P value <0.05. Dnase1 activity was lower in patients with SLE than in the control group: 13.69 ± 8.52 μg/mL vs 24.75 ± 12.32 μg/mL, respectively (P < 0.005). No statistical relationship was found between DNase1 activity and disease evolution time, hypertension, presence of absolute or relative proteinuria, SLEDAI, new clinical manifestations, anti-Ro antibodies, anti-La antibodies, anti-RNP antibodies, anti-DNA antibodies, anti-cardiolipin antibodies, lupus anticoagulant, or with the treatment pattern received by the patients. Although important differences in DNase1 activity were found between patients with or without anti-Sm antibodies, they did not reach statistical significance. DNase1 activity was significantly lower in patients with SLE. Nevertheless, we did not find further relationships with any other of the epidemiological, clinical, immunological or therapeutical variables considered.

Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in a patient with systemic lupus erythematosus

We present the case of a 57-year old female patient diagnosed with systemic lupus erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo-obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with malignant or litiasic obstruction is reported. The combination of bile duct associated with CIPO in a patient with lupus has not been previously reported in the literature and it probably suggests a smooth muscle dysmotility.

Echocardiography at diagnosis of antiphospholipid syndrome provides prognostic information on valvular disease evolution and identifies two subtypes of patients

The evolution of valvular disease in antiphospholipid syndrome (APS) is barely known. In order to evaluate whether the presence or absence of valvular disease at the time of diagnosis of APS, assessed by an initial echocardiogram, predicts its subsequent evolution, we performed a prospective cohort study. We included 53 patients with APS. An initial transthoracic echocardiogram was performed on patients at the time of diagnosis of APS. Serial echocardiograms were conducted along a 12-year follow-up. Final echocardiograms were used for comparative purposes. We started with 29 patients (54%) with and 24 (45%) without valvulopathy at initial echo. At the final echocardiogram, 27 of 29 patients with initial valvulopathy continued to have valvular disease (a 93% observed likelihood), and 22 of 24 patients without initial valvulopathy demonstrated an absence of valvular disease (a 91% observed likelihood). Patients with valvulopathy in comparison with those without presented more arterial thrombotic events (69% vs. 20%, P < 0.001), atherosclerotic risk factors (62% vs. 29%, P = 0.01), livedo (48% vs. 16%, P = 0.01) and migraine (41% vs. 12%, P = 0.02). We have identified two subtypes of APS patients with and without valvulopathy by defining differential clinical features and with little crossover in valvular involvement over a long follow-up period, giving a high prognostic value to the initial echocardiographic assessment. Lupus (2010) 19, 575—582.

Cardiac manifestations other than valvulopathy in antiphospholipid syndrome: long-time echocardiography follow-up study.

Non‐valvular cardiac disease in the antiphospholipid syndrome (APS) has been scanty studied. We wanted to assess the prevalence and evolution of left myocardial disease, pulmonary hypertension and intracardiac thrombi in a cohort of APS patients.

Acquired haemophilia A: Successful treatment with immunosuppression, methylprednisolone pulses and oral cyclosporin

Acquired haemophilia A: Successful treatment with immunosuppression, methylprednisolone pulses and oral cyclosporin -

Idiopathic retroperitoneal fibrosis: IgG4 infiltration in a cohort of Spanish patients

Sections were stained with haematoxylin and eosin as well as for Masson’s trichrome. Immunostaining for IgG4 was performed on 4-μm-thick paraffin-embedded human surgical biopsy sections using as the primary antibody a mouse anti-human IgG4 monoclonal antibody (clone MC011, the Binding Site, Birmingham, UK). Sections were also immunostained for anti-CD4 (clone 4B12, Master Diagnostica, Granada, Spain; commercial pre-concentrated dilution 1:2) and anti-CD8 (clone C8/144B, Dako Cytomation, Glostrup, Denmark; dilution 1:50) antibodies using an autostainer (Bond-Max Leica, Wetzlar, Germany). Immunohistochemistry slides were evaluated by two independent pathologists; discordant cases were re-evaluated. IgG4-positive plasmacytes were counted in 3 different high-power fields (hPF) at 400× for each specimen in the most prominently inflamed areas, and the results were compared. the stained cell recount was performed using Soft Imagin System Cell-B (Olympus, Spain). Nineteen patients were male. All patients were of Caucasian race/ethnicity except a North African subject. Mean ± standard deviation age at diagnosis was 51.8 ± 16.4 years. Mean time elapsed from onset of symptoms to diagnosis was 5.2 ± 5.13 months. histopathological features of the studied patients are shown in table 1 and Fig. 1. thirteen surgical biopsies were recovered. All patients presented 2 or more of the characteristic pathological features proposed by Deshpande et al. [4] (lymphoplasmacytic infiltrate, storiform fibrosis and obliterative phlebitis). IgG4-positive immunostaining was found in 8 individuals (61.5 %), but only 3 patients presented >30 IgG4 plasma cells/hPF × 400 (mean 45.4; range 37.2–65.5). the other 10 subjects showed <30 IgG4 plasma cells/hPF × 400 (mean 3.8; range 0–29.8). Only three patients fulfilled the requests for histological highly Sir,