PubMed Health⌕ Search

Biomedical subjects

M A Khamashta

Publications and source records attributed to M A Khamashta.

At least 19 recordsLinked to original sources
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

Thymulin and its role in immunomodulation.

Even though thymulin was isolated, sequenced and characterised some 20 years ago and later identified as a thymic hormone involved in immunomodulation, much more work is still required to further understanding of the mechanisms of action(s) of this peptide. Since the observation, by a semiquantitative bioassay, of diminished levels of thymulin in immunodeficiency and autoimmune disease, new data obtained by radioimmunoassay have not only confirmed previous observations but also demonstrated that thymulin plays a role in the interaction between the immune system and the neuro-endocrine system. In this paper we give an up to date account of recent developments in research into the role of thymulin in immunomodulation.

Amino Acid Sequence↗
PubMed1992

Anti-myeloperoxidase autoantibodies in patients with necrotizing glomerular and alveolar capillaritis.

We conducted a prospective study of 651 Mediterranean patients from Catalonia (Spain) with well-defined forms of systemic vasculitis, connective tissue diseases, and renal and pulmonary disorders to determine the prevalence and clinical value of antineutrophil cytoplasmic autoantibodies (ANCA) with myeloperoxidase (MPO) specificity (MPO-ANCA). ANCA were first tested by indirect immunofluorescence on ethanol-fixed neutrophils. When a positive result was obtained, then MPO-ANCA were identified by performing the immunofluorescence assay again on neutrophils from a voluntary donor known to have a complete and selective deficiency of MPO. This disorder was detected by automated flow cytochemistry with the Technicon system and was further verified by cytochemical and biochemical studies. We detected MPO-ANCA in 61 of 70 (87%) patients with a perinuclear pattern (p-ANCA), but in none of 25 with a cytoplasmic pattern (c-ANCA). These results were corroborated by enzyme-linked immunosorbent assay (ELISA) using human purified MPO as a substrate. On immunofluorescence microscopy, all patients with MPO-ANCA were found to have a typical and restrictive immunostaining pattern. In our study, while c-ANCA were mainly found in patients with biopsy-proven Wegener's granulomatosis, MPO-ANCA identified those with idiopathic and polyarteritis nodosa-associated necrotizing and crescentic glomerulonephritis. In addition, pulmonary hemorrhage with necrotizing alveolar capillaritis as the main morphologic substrate occurred frequently among patients with MPO-ANCA, including three affected by polyarteritis nodosa and three who had pulmonary hemorrhage as the only clinical finding. On the other hand, these antibodies could be also detected in 30% of patients with a proven diagnosis of anti-glomerular basement membrane (GBM) disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Reassessing the status of antiphospholipid syndrome in systemic lupus erythematosus.

The antiphospholipid syndrome was initially described in 1986. To reassess the validity of antiphospholipid antibodies in systemic lupus erythematosus (SLE), 95 patients with SLE were studied. Their antiphospholipid antibody profile was analysed and correlated with clinical findings such as thrombosis, abortions, or thrombocytopenia. A low prevalence of these antibodies was found (13 patients; 14%) with a high specificity for thrombosis (92%) and abortions (92%). The importance of anticardiolipin antibodies as a risk factor for thrombosis or abortions, or both, in patients with SLE is reaffirmed by this work.

Abortion, Spontaneous↗
PubMed1992

Antiphospholipid antibodies and HLA associations in primary Sjögren's syndrome.

Blood samples from 65 patients with primary Sjögren's syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjögren's syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjögren's syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjögren's syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjögren's syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjögren's syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjögren's syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement.

Female↗
PubMed1992

Antiphospholipid antibodies in homozygous sickle cell disease.

Serum samples from 108 unselected Jamaican patients with homozygous sickle cell disease and 116 control subjects with normal haemoglobin were screened for the presence of antiphospholipid antibodies. Slightly increased levels of IgG antiphospholipid antibodies were found in nine patients with sickle cell disease and in none of the control subjects. Serial control samples confirmed the increased levels of antiphospholipid antibodies. A comparison of the haematological and clinical features of patients with positive and negative antiphospholipid sickle cell disease did not highlight any differences between the groups.

Adolescent↗
PubMed1992

Isotype profile and clinical relevance of anticardiolipin antibodies in Sjögren's syndrome.

The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear.

Adult↗
PubMed1992

Distribution of two common idiotypes of anticardiolipin antibodies in sera of patients with primary antiphospholipid syndrome, systemic lupus erythematosus and monoclonal gammopathies.

The frequency of two common idiotypes of anticardiolipin antibodies (aCL) was determined in sera from three groups of subjects, patients with systemic lupus erythematosus (SLE), with primary antiphospholipid syndrome (PAPS) and with monoclonal gammopathies (MG), as compared to normal population. The idiotype 1.10, which was derived from a patient with active SLE and antiphospholipid syndrome, was found more frequently among patients with PAPS (10.5%, 10.5% and 22.2% in MG, SLE and PAPS, respectively) than the idiotype H3, which was derived from a human hybridoma monoclonal aCL generated from a healthy subject immunized with tetanus and diphtheria. The latter idiotype was detected in 8.7%, 6.5% and 11.7% of patients with MG, SLE and PAPS, respectively. Incidental findings in this study include a high prevalence of aCL among patients with MG (23%) and a high prevalence of anti-dsDNA antibodies, detected only by a sensitive enzyme-linked immunosorbent assay, among patients with PAPS. Our results indicate that idiotypic diversity exists among aCL derived from different sources. Some of these cross-reactive idiotypes may be more pathogenic than others.

Adult↗
PubMed1992

The heart and antiphospholipid antibodies in MRL-lpr/lpr mice.

Our objective in this study was to determine possible associations between antiphospholipid antibodies (aPL) and histologically defined heart valve lesions in the MRL-lpr/lpr mouse, a suitable model for the antiphospholipid syndrome (APS). At monthly intervals, from 2 to 6 months of age, three MRL-lpr/lpr mice (two with anticardiolipin antibodies, one without) and two sex- and age-matched Balb/c mice (controls) were sacrificed for histological studies. Serum binding to phospholipids and DNA was studied at this time. We found thickened heart valves in 68% of MRL-lpr/lpr mice and in 80% of Balb/c mice, and no association with any of the antibodies tested was found. No evidence of coronary vasculitis or thrombi was found in any of the mice studied. Platelet counts in MRL-lpr/lpr mice were significantly lower (640.550 +/- 211.818 x 10(6)/ml) than in Balb/c mice (780.0 + 112.5 x 10(6)/ml) (p < 0.05), and no association was found between platelet counts and aPL. In this model of murine APS, aPL bear no importance in heart valve pathology.

Animals↗
PubMed1992

Lack of association between anticardiolipin antibodies and migraine in systemic lupus erythematosus.

We carried out a prospective study of the prevalence and characteristics of anticardiolipin antibodies (aCL) and migraine on 103 consecutive patients with systemic lupus erythematosus (SLE) derived from three European referral university centers. We also included a control group of 58 patients with migraine not associated with SLE. We interviewed all patients using a data collection form designed to provide a complete record of the clinical characteristics of headache. Fifty-four (52%) patients with SLE suffered recurrent headache. We diagnosed migraine in 32 patients, tension headache in 21, and cluster headache in one. Thirty (29%) patients with SLE had aCL. Migraine was present in five patients with aCL and in 27 patients without aCL (17% versus 37%, p = 0.07). No migraine control patient had aCL. Our study highlights the frequency of headache in SLE, but does not support an association between the presence of aCL and migraine in this disease.

Adolescent↗
PubMed1992

Systemic lupus erythematosus in males: analysis of clinical and laboratory features.

We analysed the clinical and laboratory features of 16 males in comparison with 231 females from a series of 247 unselected patients with systemic lupus erythematosus (SLE). There was no significant difference between male and female patients with regard to age at onset and age at diagnosis. Apart from serositis, which was found to occur at a significantly higher frequency in male patients, the incidence of clinical features at disease onset was similar in both sexes. Analysis of clinical findings during the evolution of the disease showed no significant difference between male and female patients. Similarly, no significant immunological difference was found between the two groups. Thus, except for a higher frequency of serositis as the presenting symptom in males, we could not find any notable differences in clinical and serological parameters of male and female patients with SLE.

Adolescent↗
PubMed1992

Clinical, endoscopic, immunologic, and therapeutic aspects of oropharyngeal and esophageal candidiasis in HIV-infected patients: a survey of 114 cases.

The medical records of 114 consecutive HIV-infected patients with oropharyngeal and esophageal candidiasis, in whom esophagoscopy was performed, were reviewed. Esophageal candidiasis and isolated oral candidiasis were found in 75% and 25% of patients, respectively. Esophageal candidiasis was the AIDS-defining illness in 65 patients and dysphagia was the commonest symptom, but asymptomatic Candida esophagitis was observed in 43% of them. Symptoms were present in six patients with oropharyngeal candidiasis; three of them had a normal esophagoscopy and the other three had acute nonfungal esophagitis. Invasive fungal esophagitis was confirmed by biopsy in 47/74 patients (64%). The patients with esophageal candidiasis had lower CD4+ cell counts (129/microliter) and CD4:CD8 ratios (0.23) than those with oropharyngeal candidiasis (CD4 179/microliter; CD4:CD8 0.35). Thirty-six patients with esophageal candidiasis were treated with fluconazole, 100 mg/daily, for 28 days, and another 34 patients received the same dose for 10 days. A similar efficacy was seen in both regimens, but a higher incidence of oropharyngeal fungal colonization and liver dysfunction was observed in the longer therapy (p < 0.001). We conclude that asymptomatic C. esophagitis is common in HIV-infected patients. Patients with oropharyngeal candidiasis may complain of esophageal symptoms; it could be due to superficial C. infection or another not-identified opportunistic infection. More severe immunologic impairment was required to develop esophageal candidiasis than oropharyngeal candidiasis. A short course of 10 days of fluconazole therapy could be the standard regimen for the treatment of C. esophagitis in AIDS.

Biopsy↗
PubMed1992

HLA-DP genotyping in patients with systemic lupus erythematosus: correlations with autoantibody subsets.

In order to ascertain whether the HLA-DP locus plays a role in the genetic predisposition for systemic lupus erythematosus (SLE), 42 patients with SLE were typed for 17 different DPBeta haplotypes by locus specific amplification followed by allele specific oligonucleotide hybridization. Sera from the same patients were assayed for the presence of autoantibodies to Sm, RNP, Ro, La and of anticardiolipin antibodies (aCL). DPB1*0301 and DPB1*1401 were increased in patients compared with 107 healthy controls, mainly in those anti-Sm/RNP positive and aCL positive. Remarkably, DPB1*1401 and DPB1*0301 have a nearly identical nucleotide sequence, suggesting that an epitope shared by their membrane products is of major importance for the DP related susceptibility to SLE.

Adult↗
PubMed1992

Low dose methotrexate treatment in adult Still's disease.

Six patients with adult Still's disease who had either failed to respond to or had adverse effects from previous therapy were given weekly low dose methotrexate (MTX) therapy. They were followed for 4-28 months (mean 14 +/- 9 months). At 12 months of therapy 3 patients were evaluated as having a complete response. One patient had a partial response to MTX after 7 months. Therapy was discontinued in 1 patient at 4 months due to flares of rash and arthralgias after each MTX administration. One patient failed to respond to therapy despite maximum dosage, but was able to reduce his corticosteroid dose. MTX may be a useful therapy to consider in patients with adult Still's disease who are resistant to conventional therapy and may allow a reduction in the concomitant dose of corticosteroids.

Adult↗