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P Langevitz

Publications and source records attributed to P Langevitz.

At least 55 records · Page 3Linked to original sources
PubMed1999

A novel 26 kilodalton antigen expressed on the surface membrane of activated T cells.

We have identified and characterized the tissue distribution of the antigen recognized by a novel monoclonal antibody (mAb) 1B10, raised against an activated gammadelta T cell clone. Immunohistochemistry of tissue sections, and analysis of single cell suspensions by flow cytometry revealed that mAb 1B10 weakly reacted with <6% of normal human peripheral blood mononuclear cells (PBMC). After 5-6 days of in vitro culture of PBMC activated with phytohemagglutinin (PHA), 55% of the CD4+ and 25% of the CD8+ T cells became 1B10+. 1B10 expression was maintained on long term cultured interleukin 2 (IL-2)-dependent T cell receptor (TCR) alphabeta+ and gammadelta+ clones, and importantly, in contrast to resting T cells, the majority of in vivo activated synovial T lymphocytes from a patient with rheumatoid arthritis were 1B10+. In addition, myelo-monocytic U927 cells, tissue macrophages and some epithelia and fibroblasts were found to react with mAb 1B10. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of molecules immuno-precipitated by mAb 1B10 from radio-iodinated cell surface membrane lysates of T lymphocyte and U937 cells revealed 26 and 29 kiloDalton (kDa) glycoproteins respectively. In conclusion, mAb 1B10 recognizes a novel < > appearing 26 kDa T cell activation antigen that may be useful for further studies of activated T cells in health and disease.

Antibodies, Monoclonal↗
PubMed1999

Pulmonary associations in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome expressed by acute episodes of fever and painful manifestations. In this report, the pulmonary manifestations of FMF are reviewed, the most prominent of which are chest attacks due to pleuritis. Nephropathic amyloidosis of the AA type, which complicates FMF in most untreated patients, may progress to affect other organs, including the lungs, but this rarely produces noticeable symptoms. The common association between FMF and vasculitis makes pulmonary hemorrhage, infarction, or infiltrates highly possible. These complications, however, have been reported only rarely. Asthma was found to occur less often than expected in patients with FMF, but methodologic faults make this finding doubtful. Finally, the occurrence of mesothelioma in five patients with FMF who were not exposed to asbestos suggests a role for recurrent FMF serositis in the pathogenesis of this malignancy.

Amyloidosis↗
PubMed1999

Relapsing acute pancreatitis induced by re-exposure to the cholesterol lowering agent bezafibrate.

We report a 75-yr-old patient, who presented three times with acute pancreatitis, accompanied by high temperature, shock, and multiorgan involvement and associated each time with exposure to the cholesterol lowering agent bezafibrate. Extensive workup excluded other possible causes for recurrent pancreatitis in this patient, further supporting bezafibrate as the cause of the patient's acute illness. Based on the short time elapsing between rechallenge and development of manifestations and the specific features of the attacks, we proposed hypersensitivity to bezafibrate as the underlying mechanism. The present report includes, for the first time, bezafibrate among definite causes of acute pancreatitis.

Acute Disease↗
PubMed1999

Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin.

BACKGROUND: Autoimmune vasculitides cannot always be controlled by steroids and immunosuppressive drugs. Intravenous immunoglobulin (IVIg) treatment was found beneficial in several vasculitides including systemic and organ-specific diseases. In this article we tested whether the beneficial clinical response of IVIg treatment in vasculitides was accompanied by a decrease in vasculitis-associated autoantibody levels. METHODS: Ten patients diagnosed as having vasculitis were treated with high-dose (2 g/kg) IVIg monthly, in a 5-day schedule. In all the patients, other therapeutic measures failed to control disease progression prior to IVIg treatment. Each patient received between 1 and 6 treatment courses. All patients were evaluated for the levels of 5 autoantibodies (Abs) related to vasculitis before and after each treatment course. RESULTS: In 6 out of the 10 patients, a beneficial clinical response followed IVIg treatment. Moreover, no treatment-related adverse effects were observed in any of the patients. Anti-myeloperoxidase antibodies and cytoplasmic-antineutrophil cytoplasmic antibodies levels decreased concomitantly with the clinical improvement observed in the patients with Churg-Strauss vasculitis and Wegener's granulomatosis, respectively. Levels of cytoplasmic-antineutrophil cytoplasmic antibodies (ANCA) with specificity for bacteridial/permeability-increasing protein and human lysosomal-associated membrane protein increased after each treatment course, but returned to normal values before the following one. CONCLUSIONS: When other therapeutic measures, such as immunosuppressive therapy, fails to control disease manifestations in patients with vasculitides, IVIg is a possible effective intervention method with a high response rate. IVIg probably exerted its effects on disease progression via different mechanisms. Among these mechanisms, a decrease in relevant Ab levels is often found (probably by anti-idiotypes in IVIg), and thus ANCA levels are expected to associate with disease activity.

Adult↗
PubMed1999

A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response.

OBJECTIVE: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels. METHODS: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course. RESULTS: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 patients evaluated before and after IVIg, mean SLAM score decreased from 19. 3+/-4.7 to 4+/-2.9 (P<0.0001). There was a tendency towards abnormal levels of complement and Abs before IVIg courses among the treatment responders compared with the non-responders, and similarly the former tended to have normalization of their abnormal levels more than the latter. These differences were found statistically significant only with respect to C4 and SS-A or SS-B levels before IVIg courses. CONCLUSION: IVIg has a high response rate among SLE patients. A combination of clinical manifestations, Abs and complement levels may aid in the future in predicting who among SLE patients will benefit more from IVIg treatment.

Adult↗
PubMed1999

Beta2 glycoprotein I containing immune-complexes in lupus patients: association with thrombocytopenia and lipoprotein (a) levels.

In this study we determined the prevalence and clinical associations of immune-complexes-containing beta-2-glycoprotein I (beta2GPI) in randomly selected SLE patients. We studied 38 consecutive SLE patients attending the Rheumatology Unit. Previous arterial or venous-thrombosis were documented by the appropriate diagnostic test. Lipid profile including total cholesterol, LDL, VLDL, HDL and Lp(a) levels were determined from the sera of the fasting patients. Antibodies to cardiolipin, oxidized LDL and beta2GPI were detected employing ELISA. Beta2GPI containing IgG immune-complexes were assayed by using a dot-blot assay. Fourteen SLE patients (36.8%) were found to be positive for the presence of IgG anti-beta2GPI antibodies. Ten of the SLE patients (26.3%) were found to have high levels of beta2GPI containing immune-complexes. There was a positive correlation between beta2GPI-IC levels and the occurrence of thrombocytopenia in the patients (P < 0.05). Furthermore, patients with SLE and venous thrombosis had higher levels of beta2GPI-IC when compared with thrombosis-free patients or with healthy controls (P < 0.05). Patients with higher Lp(a) levels (> 50 mg/dl) possessed higher levels of beta2GPI-IC as compared with patients with lower Lp(a) concentration (< 20 mg/dl) (P < 0.05). These results suggest that IC-containing beta2GPI can help in defining a subpopulation of SLE patients with increased risk of thrombocytopenia and further aid in resolving mechanisms of immune-mediated tissue damage.

Adult↗
PubMed1999

Atherosclerosis-related markers in systemic lupus erythematosus patients: the role of humoral immunity in enhanced atherogenesis.

Systemic Lupus Erythematosus (SLE) patients experience premature atherosclerosis. A deranged lipid metabolism and use of immunosuppressive medications accounts partially for the accelerated process. The role of autoimmunity in atherosclerosis has recently been highlighted. Autoantigenic determinants thought to play a role in the development of atherosclerosis include: modified lipoproteins, heat shock proteins and beta2-glycoprotein I (a target of 'autoimmune' anticardiolipin antibodies). In this present work we determined autoimmune markers which may be associated with premature atherosclerotic process found in SLE patients. We have found that antibodies to oxLDL were raised in the sera of lupus patients and cross-reacted with cardiolipin and with beta2GPI. OxLDL containing immune-complexes of the IgG and IgM isotypes were both elevated in the SLE patients as compared with healthy controls. Patients with high Lipoprotein (a) concentrations (>30 mg/dl) had higher levels of IgM oxLDL-containing immune-complexes. IgM but not IgG anti-HSP-65 antibodies were elevated in the lupus patients and levels of oxLDL containing immune-complexes correlated positively with the presence of anti-HSP 65 antibodies. Lysophosphatidylcholine (LPC) is a peroxide-derivative formed during LDL oxidation, was shown to evoke a humoral response in healthy subjects. Antibodies to lysophosphatidylcholine of the IgG but not the IgM isotype were reduced in SLE patients compared with controls, suggesting it may be 'consumed' into oxLDL containing immune complexes. Therefore, SLE patients exhibit a humoral autoimmune response towards the antigenic candidates incriminated in the progression of atherosclerosis. These findings may help identify factors that are involved in accelerating atherogenesis in SLE patients.

Adult↗
PubMed1999

Treatment of chronic bilateral pleural effusions with intravenous immunoglobulin and cyclosporin.

A 48 y old woman with unremarkable medical history was admitted with bilateral pleural effusions; even though the fluid was drained, it re-accumulated and necessitated many repeated drainages in the following 2.5 y (56 hospitalisations). The patient underwent an extensive diagnostic work-up that disclosed elevated serum antinuclear antibodies, serum anti-dsDNA antibodies, pleural fluid anti-dsDNA and decreased pleural fluid C3 and C4. During that period she has been treated with a variety of immunomodulating agents, several pleural talcage and pleurectomy, without any apparent response. Thereafter, she received six courses of IVIg (2 g/kg body weight) in monthly intervals, followed by four months treatment with cyclosporin. This treatment resulted in gradual and eventually complete disappearance of the pleural effusion, and now after more than 2 y the patient is free of symptoms and receives no further medications.

Antibodies, Antinuclear↗
PubMed1999

Positive antineutrophil cytoplasmic antibodies-associated vasculitis presenting with hemoptysis and a mediastinal mass.

A patient with end-stage renal failure, due to IgA nephropathy, was found to have a mediastinal mass. Biopsy specimen of the mass showed a necrotizing vasculitis. Antineutrophil antibodies to myeloperoxidase were strongly positive. To our knowledge, no case of a mediastinal mass due vasculitis has been reported in the literature, and our observation should lead to broadening of the spectrum of clinical manifestations of vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q. In another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P < 0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease.

Amyloidosis↗
PubMed1999

Activation of the cytokine network in familial Mediterranean fever.

OBJECTIVE: To elucidate the role of cytokines in the pathogenesis of familial Mediterranean fever (FMF), an inherited disease characterized by attacks of serosal membrane inflammation. METHODS: Blood samples were obtained from patients with FMF during attacks and remission. The cytokine concentrations in plasma and in supernatants from whole blood stimulated by bacterial lipopolysaccharide (LPS) were determined. RESULTS: There were 27 patients with FMF, of whom 8 were studied during attacks, 9 during remission and 10 during both attack and remission. FMF attacks did not affect levels of plasma tumor necrosis factor-alpha (TNF-alpha) or interleukin 1beta (IL-1beta). In contrast, compared to remission, FMF attacks were associated with significantly higher mean levels of plasma IL-6 [8.4 pg/ml, 95% confidence interval (CI) 7.8-8.9 in remission vs 59 pg/ml, CI 21.4-96.7 during attacks; p=0.0005], sTNFr p55 (1.3 ng/ml, CI 1.2-1.4, vs 1.98 ng/ml, CI 1.6-2.3; p=0.005), and sTNFr p75 (2.9 ng/ml, CI 2.5-3.3, vs 4.09 ng/ml, CI 3.2-4.9; p=0.0249). The TNF-alpha, IL-1beta, and IL-6 content in supernatants derived from LPS stimulated blood cells was not modified by the attacks of FMF. Significant lower TNF-alpha release in LPS stimulated whole blood was detected in patients who were sampled in a later stage of the attacks (r=-0.54, p=0.047). CONCLUSION: Our results suggest that the cytokine network is activated during attacks of FMF. IL-6 appears to play an important role in the evolution of FMF attacks. Whether TNF-alpha or IL-1beta has a function in initiating the attacks remains to be established.

Acute Disease↗
PubMed1999

Elevated homocysteine levels in patients with Raynaud's syndrome.

OBJECTIVE: Patients with Raynaud's phenomenon (RP) have vasomotor dysregulation, the etiology of which has not yet been elucidated. We investigated plasma levels of homocysteine and folate in patients with primary or secondary RP in comparison with healthy subjects. METHODS: Plasma from patients with RP, either primary (n = 10) or secondary to scleroderma (n = 10), and from healthy subjects (n = 20) was obtained for homocysteine determination using high performance liquid chromatography. RESULTS: Patients with primary and secondary RP had significantly higher homocysteine concentrations (mean 15.5 +/- 4.1 and 11.6 +/- 6.2 micromol/l, respectively; p < 0.05) compared to healthy individuals (mean 5.9 +/- 2.0 micromol/l). Patients with primary RP had significantly lower plasma levels of folate in comparison with patients with secondary RP or healthy individuals. CONCLUSION: This is the first study to show higher plasma levels of homocysteine in patients with RP. Given the obscure etiology of this disorder, these findings may provide new clues in the understanding of vasomotor dysfunction in RP.

Adult↗
PubMed1999

Quality of life in systemic lupus erythematosus: a controlled study.

OBJECTIVE: To assess the quality of life (QOL) of patients with systemic lupus erythematosus (SLE) and to compare it with that of healthy women and patients with primary fibromyalgia (FM). METHODS: QOL was evaluated using the QOL scale, which includes 16 items, each scored on a 7 point scale. Healthy controls were chosen from hospital personnel. RESULTS: The study population comprised 75 female patients with SLE, 50 healthy women, and 30 women with primary FM. Compared to controls, patients with SLE had significantly lower scores for the health, work, active recreation, and independence items. The QOL scores were not associated with disease activity. Patients with SLE and FM had significantly lower scores for the health related items compared with patients with SLE without FM. CONCLUSION: The QOL of patients with SLE was found to be impaired compared with controls. FM adversely affects the QOL of patients with SLE.

Adult↗
PubMed1998

Target recognition of beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of beta2GPI in antibody binding.

Beta2-glycoprotein I (beta2GPI) is an absolute requirement for the binding of autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target recognition of human beta2GPI by IgG derived from two patients with primary and two with secondary antiphospholipid syndrome. The total IgG serum fractions and beta2GPI affinity-purified IgGs were assessed by using various domain-deleted mutants (DM) of human beta2GPI (DMs: I-III, I-IV, II-V, III-V, IV-V, and V) and mouse mAbs against individual beta2GPI domains. The four IgGs bound slightly to CL in the absence of beta2GPI and showed increased binding in the beta2GPI presence. Following affinity purification of the IgGs on a beta2GPI column, reactivity toward CL was absent. DMs containing domain V inhibited the binding of biotinylated beta2GPI to CL. The addition to CL-coated plates of DM V, but not the other DMs, reduced the binding of all four IgGs. The anti-beta2GPI IgGs bound only to complete beta2GPI and DM I-IV coated on the plates. The binding to plate-adsorbed beta2GPI could be inhibited by complete beta2GPI and DM I-IV, the latter being a more efficient inhibitor. Further, the human anti-beta2GPI IgGs could compete with the binding to beta2GPI of Cof-21 mouse mAb (directed at domain IV), but not with the two other mouse mAbs. The results suggest that some "autoimmune:" beta2GPI-dependent anticardiolipin Abs recognize a beta2GPI target that is distinct from the CL-binding site in domain V. The target site for some antiphospholipid syndrome IgGs appear to reside in domain IV of beta2GPI.

Animals↗
PubMed1998

Clinical differences between North African and Iraqi Jews with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The gene causing this disease, designated MEFV, was mapped to the short arm of chromosome 16, but has not yet been cloned. North African and Iraqi Jews constitute the two largest population groups suffering from the disease in Israel. In this report we compared the severity of the disease between these two populations. North African Jews were found to have a more severe disease manifested by an earlier age of onset, an increase in frequency and severity of joint involvement, a higher incidence of erysipelas-like erythema, and a higher dose of colchicine required to control symptoms. The involvement of additional genes, environmental factors, and different mutations in MEFV, may explain the clinical variation in disease severity between these two population groups.

Adult↗
PubMed1998

Outcome of pregnancy in three patients with primary antiphospholipid syndrome after stroke.

OBJECTIVE: Ischemic stroke is the most common neurological manifestation in patients with antiphospholipid syndrome (APS). Pregnancy in APS patients markedly increases the risk of thrombosis. There is no data on pregnancy outcome in patients with APS with a history of an ischemic stroke. We report our experience with three APS patients with a history of stroke who had successful pregnancies and deliveries. PATIENTS: Three patients with APS and previous stroke were treated with small doses of aspirin and anticoagulants during pregnancy. RESULTS: The patients remained free of attacks of cerebral ischemia during their pregnancies and at follow-up periods of 1 to 4 years. CONCLUSIONS: Successful pregnancy and delivery is possible in APS patients with a history of stroke, treated with low-dose aspirin and anticoagulants. A previous episode of cerebral ischemia should not be considered an absolute contraindication for an APS patient to become pregnant.

Adult↗