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Biomedical subjects

D D'Cruz

Publications and source records attributed to D D'Cruz.

At least 55 records · Page 3Linked to original sources

Pneumonitis in a lupus twin pregnancy: a case report.

We describe a patient with systemic lupus erythematosus (SLE), whose pregnancy was complicated by fulminant lupus pneumonitis and pericarditis. Maternal disease responded to therapy and twin girls were delivered, both with thrombocytopenia, one of whom died of an intraventricular haemorrhage. Pneumonitis is a rare complication of lupus in pregnancy which may be fatal. We suggest patients with previous severe pneumonitis should have lung function tests at the onset of pregnancy, and treatment be modified to suppress flare if there is any indication of severe pneumonitis in early pregnancy.

Adult↗

Anti-endothelial cell antibodies, endothelial proliferation and von Willebrand factor antigen in Behçet's disease.

Endothelial cell dysfunction has previously been demonstrated in Behçet's disease which has vasculitic features. In this study we investigated anti-endothelial cell antibodies (AECA) and von Willebrand factor antigen (vWF) levels in patients with Behçet's disease. In vitro effects of patient sera on endothelial cell proliferation were also evaluated. AECAs were present in 29% of 70 Behçet's disease patients (Binding Index: 25 +/- 29% vs 9 +/- 7% in normal controls, p < 0.005). 95% of AECA positive patients were clinically active compared to 74% of AECA negative patients (p = 0.04). Among specific organ manifestations only active arthritis correlated with AECA positivity (6 of 7 patients vs 14 of 63, p = 0.002). AECA positive patients had a significantly higher mean ESR (37 +/- 24 mm/h vs 21 +/- 17 mm/h, p:0.006). Mean vWF levels were also significantly higher in patients compared to controls (166 +/- 75% vs 84 +/- 34%, p < 0.0001). No correlations were observed between AECA titres and vWF levels. No significant differences were observed between patients and controls when endothelial cell proliferation was studied (Proliferation Index: 1.25 +/- 0.28 vs 1.12 +/- 0.25, p = 0.5). Our results suggest that AECA may be related to disease activity in Behçet's disease. The presence of vWF, even in patients in complete remission, might be related to factors other than endothelial damage for vWF release from endothelial cells.

Adolescent↗

Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis associated with anti-thyroid drug treatment.

Two cases of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis following treatment with propylthiouracil and carbimazole are described. Both patients had crescentic glomerulonephritis proven by renal biopsy and responded to immunosuppressive therapy and withdrawal of the anti-thyroid drugs. Though systemic vasculitis associated with propylthiouracil is reported, this is the first report to our knowledge of renal biopsy-proven vasculitis associated with either of these drugs.

Adult↗

Autoantibodies against endothelial cells, extracellular matrix, and human collagen type IV in patients with systemic vasculitis.

Endothelial cells and subendothelial matrix (ECM) are involved in the pathogenesis of vasculitis. Exposure of the ECM following vascular damage may promote further immune and inflammatory response. To investigate this, we studied the prevalence of antibodies against endothelial cells (AECA), ECM, and its major component collagen type IV in systemic vasculitis patients. Seventy-one percent of patients had AECA (binding index, means +/- SD: 64.8 +/- 48.1%; normal controls: 8.9 +/- 6.9%, P < 0.001). Anti-ECM and anti-collagen type IV antibodies were also significantly higher in patients compared to normals (anti-ECM: 28.6 +/- 29.6% vs 9.0 +/- 11.3%, P < 0.002; anti-collagen type IV: 23.5 +/- 20.3% vs 8.1 +/- 9.1%, P < 0.002). AECA correlated with anti-ECM (r = 0.75, P < 0.0001) but not with anti-collagen type IV. Anti-ECM correlated with anti-collagen type IV (r = 0.45, P < 0.01). Positivity of cytoplasmic anti-neutrophil cytoplasmic antibodies (cANCA) was significantly lower in patients positive for anti-ECM and/or anti-collagen type IV antibodies (58% vs 11%, P = 0.048). AECA binding was partially reduced with ECM incubation by 25.1%. The addition of heparin caused a dose-dependent inhibition of binding activity (19.2-30.6%) in the AECA ELISA. These results support the hypothesis that there is a humoral response against ECM components in addition to endothelial cells in systemic vasculitis patients which might have pathological significance in vascular damage.

Adult↗

Characterization of the endothelial surface proteins recognized by anti-endothelial antibodies in primary and secondary autoimmune vasculitis.

The antigenic structures recognized by anti-endothelial cell antibodies (AECA) in sera from 10 Wegener's granulomatosis (WG) and 12 systemic lupus erythematosus (SLE) patients with signs of vasculitis were characterized by immunoprecipitation of selectively radiolabeled surface membrane proteins from human umbilical vein endothelial cells. Electrophoretic analysis of the immunoprecipitated proteins revealed reactivities against endothelial antigens ranging in size from 200 to 25 kDa. AECA antigens were not cell specific, since the same sera also reacted, at least in part, with radiolabeled human fibroblast surface proteins. The majority of WG patients displayed a constant precipitation pattern of five proteins (180, 155, 125, 68, and 25 kDa). On the contrary, AECA from SLE sera reacted with a more heterogeneous series of endothelial proteins. A group of four proteins, however, was also found in the majority of SLE sera: 200, 180, 155, and 25 kDa. In addition, some endothelial antigens were immunoprecipitated only by WG (125 kDa) or by SLE sera (200 kDa), suggesting a different endothelial reactivity in different vasculitic processes. The reaction did not involve intracellular proteins as demonstrated by the lack of reactivity of SLE sera negative for AECA but positive for anti-cytoplasmic or anti-nuclear antibodies. These data confirming that AECA recognize surface endothelial determinants further support a potential pathogenetic role for these antibodies in autoimmune vasculitis.

Antibodies↗

Allergic disorders in systemic vasculitis: a case-controlled study.

A number of the systemic vasculitides (SV) may have an allergic component although specific allergens remain unknown. We evaluated the prevalence of several types of allergy in 60 consecutive patients with SV and their families. Two control groups were studied. One included 60 healthy people and the other 60 unselected patients attending a general rheumatology clinic who did not have SV. Forty-four of the 60 patients (73%) had a history of at least one type of allergy. This was significantly higher than in either control group (P = 0.0001 and P = 0.0002). There was also a significantly higher prevalence of allergies among the families of the SV patients compared to the controls. This data supports the idea that an allergic response to an external allergen may play an important part in the aetiology of these diseases.

Adult↗

Systemic lupus erythematosus evolving into systemic vasculitis: a report of five cases.

Five patients with systemic lupus erythematosus are described who developed the disease in their second or third decade. The pattern of their disease then changed markedly and they developed the clinical features of a systemic vasculitis. The possible explanations for this transition of one connective tissue disease to another is discussed.

Adolescent↗

Environmental factors predicting nephritis in systemic lupus erythematosus.

OBJECTIVES: To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. RESULTS: Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. CONCLUSIONS: Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE.

Abortion, Spontaneous↗

[Anti-endothelial cell antibodies in systemic lupus erythematosus: association with vascular and renal lesions].

BACKGROUND: The aim of this study was to know the prevalence and characteristics of endothelial anticellular antibodies (EAA) in systemic lupus erythematosus and its relation with the clinical and immunologic manifestations of this entity. METHODS: A prospective study of 50 patients (44 females and 6 males) diagnosed with SLE was carried out. EAA and anticardiolipin antibodies (ACA) were determined by the ELISA technique, lupic anticoagulant by coagulometric techniques, antinuclear antibodies by indirect immunofluorescence, anti-DNA antibodies by the Farr technique, anti-ENA by contra-immunoelectrophoresis and the complement values by radial immunodiffusion. The statistical study was carried out by chi-square test and Fisher test. RESULTS: Positive titers of EAA were observed in 29 (58%) of the patients with SLE. The patients with EAA presented greater prevalence of both, vascular lesions (31% vs 5%, P < 0.05) and kidney involvement (62% vs 29%, p < 0.05) than those without EAA. Patients with EAA also presented a higher prevalence of antiphospholipid antibodies than patients without EAA (59% vs 10%, p < 0.001). No association was found between EAA and the titers of antinuclear antibodies, anti-DNA, anti-ENA or complement levels. CONCLUSIONS: Endothelial anticellular antibodies appear with greater frequency in patients with systemic lupus erythematosus and are more often associated with vascular and kidney involvement and with the detection of antiphospholipid antibodies suggesting that they may play an etiopathogenic role in the production of these lesions.

Adult↗

Antibodies to endothelial cells in primary vasculitides mediate in vitro endothelial cytotoxicity in the presence of normal peripheral blood mononuclear cells.

Twenty-eight out of 62 patients with Wegener's granulomatosis and micropolyarteritis display circulating antiendothelial cell antibodies (AECA) detectable by a cell surface radioimmunoassay. These antibodies do not induce an in vitro endothelial damage either alone or in the presence of fresh complement; however, 50% of IgG-AECA positive sera can be cytotoxic in the presence of human normal peripheral blood mononuclear cells (PBM) at high effector/target ratios. The specificity of the PBM-mediated cytotoxicity is supported by the absence of the phenomenon in AECA negative sera, by the disappearance of the lytic effect after absorption of AECA, and by the finding that cellular-mediated cytotoxicity can be reproduced by purified IgG-AECA positive fractions. On the contrary, polymorphonuclear leukocytes or adherent mononuclear cells are not involved in such a cytotoxic activity. AECA seem to be directed against determinants consitutively expressed on the endothelial surface since the activation of endothelial cells by interleukin-1 beta or interferon-gamma affects neither the antibody binding nor their ability to mediate 51Cr release in the presence of PBM. These findings favor the hypothesis for a possible direct pathogenetic role of circulating AECA in the in vivo vascular damage.

Adult↗

Complement factor 2 deficiency: a clinical and serological family study.

Inherited complement deficiencies are associated with a variety of connective tissue diseases. A family with inherited deficiency of complement factor 2 (C2) is described in which two family members with homozygous C2 deficiency developed cutaneous vasculitis and sicca syndrome. The other family members had heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15) haplotype. The mother had seropositive rheumatoid arthritis. Further studies showed the presence of cryoglobulins, antibodies against endothelial cells, and anticardiolipin antibodies.

Adult↗

Short term effects of intravenous pulses of cyclophosphamide in the treatment of connective tissue disease crisis.

A predominantly outpatient regimen of low dose intravenous cyclophosphamide was used to treat patients with serious progressive connective tissue diseases. Fifty five patients were treated with a total of 211 intravenous pulses of cyclophosphamide. Forty five patients had previously shown no response to a variety of other treatments. Low dose intravenous cyclophosphamide (500 mg) was given in 179 pulses and repeated pulses were given in most patients at weekly intervals for one to three weeks to induce disease remission. A good response was noted in 37 of 55 (67%) patients assessed four weeks after the pulses. Only 20 patients needed more than one such course of three pulses of intravenous cyclophosphamide during the observation period. The non-responders were characterised by longstanding disease and irreversible histological findings in renal and muscle biopsy samples. Patients with vasculitis, notably Wegener's granulomatosis, showed the most immediate response, and in most patients the amount of corticosteroids required was markedly reduced. In some patients steroids were completely stopped during the follow up period. The most striking observation of this effective but more conservative regimen was the low incidence of major side effects such as neutropenia and infections. It is concluded that low dose pulses of intravenous cyclophosphamide are well tolerated and are an effective treatment for patients with aggressive connective tissue diseases.

Adolescent↗

Anti-endothelial cell antibodies in retinal vasculitis.

Auto-antibodies to endothelial cells are found in a variety of vasculitic disorders including two diseases associated with retinal vasculitis: Behcet's disease and multiple sclerosis. In this study we have examined the prevalence of anti-endothelial cell antibodies [AECA] in 15 patients with retinal vasculitis [RV] associated with Behcet's disease, multiple sclerosis or sarcoidosis and 20 patients with idiopathic retinal vasculitis. 47% of patients with RV associated with systemic disease and 35% of patients with idiopathic RV had AECA, compared to 1% of 70 normal controls. The mean levels of AECA were similar in both groups of patients, and comparable to levels found in other systemic vasculitides.

Adult↗