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2.
Lupus ; 5(5): 418-24, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8902773

ABSTRACT

Information regarding the antiphospholipid antibody syndrome is accessible on the Internet, and encompasses both physician specific and patient specific files. The quantity and quality of data available at these sites, however, varies greatly and both search-refining and data manipulating protocols and software need improvement.


Subject(s)
Antiphospholipid Syndrome , Computer Communication Networks , Antibodies, Antiphospholipid , Humans
3.
Hum Pathol ; 26(7): 716-24, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7628842

ABSTRACT

A thrombotic microangiopathy that is identified in patients with the antiphospholipid syndrome (APS) represents only a part of the vascular pathology that can be associated with antiphospholipid antibodies (aPL). Tissues from two autopsies, four renal biopsies, two skin biopsies, and one amputated leg were obtained from six patients who met criteria for the diagnosis of APS. Three patients had systemic lupus erythematosus (SLE), one had lupus-like disease, and two had a primary APS. Five of the patients were hypertensive. Arteries of three patients disclosed fibrin thrombi along with widespread obstruction by recanalized intimal connective tissue. Small renal, leptomeningeal, and pulmonary arteries showed concentric cellular and fibrous intimal hyperplasia indistinguishable from hypertensive vascular disease. Glomerular capillary and afferent arteriolar thrombi were found in renal biopsies from two SLE patients. One of these SLE patients required a leg amputation in which the popliteal artery demonstrated thrombosis, intimal hyperplasia, and acute inflammation. The findings support clinical and experimental data that indicate aPLs cause thrombosis but suggest diversity in the pathogenetic mechanisms aPLs are capable of promoting. Inflammation seems to be rare and to accompany thrombosis. Intimal hyperplasia is particularly common. Its involvement of renal arteries may contribute to hypertension that develops in some APS patients.


Subject(s)
Antiphospholipid Syndrome/pathology , Vascular Diseases/pathology , Adult , Arteries/pathology , Female , Humans , Kidney/blood supply , Leg/blood supply , Lung/blood supply , Male , Middle Aged , Skin/blood supply , Thrombosis/pathology
4.
Arthritis Rheum ; 36(11): 1560-5, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8240432

ABSTRACT

OBJECTIVE: Lupus nephritis has often been associated with anti-DNA, but, based on the findings in eluate studies, it appears that other antigen-antibody reactions, such as those involving anti-Ro/SS-A, anti-nuclear RNP (anti-nRNP), and/or anti-Sm, may also contribute to the pathogenesis of nephritis. In the present investigation, we identified and further studied a distinctive precipitin profile present in black women with nephritis. METHODS: Longitudinal clinical and serologic studies of a cohort of university-based systemic lupus erythematosus (SLE) patients (n = 120) were carried out over an 8-year period. RESULTS: A subset of 20 black female patients was identified, of whom 8 had lupus nephritis (group I) and 12 did not (group II). Group I was characterized by a distinct precipitin profile consisting of anti-Ro/SS-A, anti-SM, and anti-nRNP, but no anti-La/SS-B. SLE disease duration at presentation was significantly shorter in group I than in group II (mean 1.94 years versus 5.21 years; P = 0.02). The distinctive precipitin profile of anti-Ro/SS-A, anti-Sm, and anti-nRNP occurred exclusively in group I patients (6 of 8, versus 0 of 12 in group II; P < 0.001). In white lupus nephritis patients, this precipitin profile was not seen. CONCLUSION: While the mechanism responsible for the relationship of this distinctive serologic profile to the development of nephritis in black female lupus patients remains to be determined, its presence may be used as a marker for severe and progressive renal disease.


Subject(s)
Autoantibodies/analysis , Black People/genetics , Lupus Nephritis/genetics , Lupus Nephritis/immunology , RNA, Small Cytoplasmic , Ribonucleoproteins, Small Nuclear , Autoantigens/immunology , Enzyme-Linked Immunosorbent Assay , Female , Histocompatibility Testing , Humans , Lupus Nephritis/pathology , Ribonucleoproteins/immunology , White People/genetics , snRNP Core Proteins , SS-B Antigen
5.
Mod Pathol ; 6(6): 644-53, 1993 Nov.
Article in English | MEDLINE | ID: mdl-8302806

ABSTRACT

OBJECTIVE: A distinctive type of chronic cerebral vasculopathy was identified in the small leptomeningeal arteries of patients with high levels of serum antiphospholipid antibodies. This study characterizes the vascular lesions and investigates their pathogenesis. DESIGN: A comparative study of cerebrovascular disease in patients dying of systemic lupus erythematosus (SLE) and the antiphospholipid syndrome. PATIENTS: Cerebrovascular disease observed in autopsies on a patient with primary antiphospholipid syndrome and a patient with SLE and antiphospholipid syndrome was compared with findings on two SLE patients who did not have serum antiphospholipid antibodies and with findings on 15 patients having diseases in which pathological changes of meningeal arteries might be anticipated or are known to occur (six patients with hypertensive cerebrovascular disease, one patient with thrombotic thrombocytopenic purpura, seven patients with marantic or bacterial endocarditis, and one patient with a left ventricular mural thrombus). Multiple blocks of brain tissue were studied by serial histologic sections and histochemical and immunohistochemical methods. Immunofluorescent and electron microscopic (EM) studies were performed on kidneys and EM studies on brain and choroid plexus in each case of antiphospholipid syndrome. RESULTS: Leptomeningeal arteries of antiphospholipid syndrome patients disclosed fibrin thrombi and widespread obstruction by a proliferation of intimal fibrous tissue or myointimal cells. The fibrous and cellular segments of obstructed arteries frequently contained fibrin thrombi and displayed varying stages of recanalization. In late stages of organization, fibrous webs were formed across arterial lumens. Obstructed arteries were traced to small infarcts localized to an underlying column of cortical gray matter. None of the tissues from antiphospholipid syndrome patients showed evidence of an active or healed inflammatory vasculitis or of vascular immune complex deposits. Recanalized thrombi, fibrous and cellular occlusions, and fibrous webs were not found in the leptomeningeal arteries of patients who did not have the antiphospholipid syndrome. CONCLUSIONS: The cerebrovascular changes of the antiphospholipid syndrome are derived from a chronic thrombotic microangiopathy. The findings support the hypothesis that antiphospholipid antibodies can cause recurring episodes of intravascular thrombosis.


Subject(s)
Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/pathology , Intracranial Embolism and Thrombosis/complications , Intracranial Embolism and Thrombosis/pathology , Adult , Aged , Aged, 80 and over , Blood Vessels/pathology , Brain/pathology , Cerebral Arteries , Cerebrovascular Circulation , Female , Humans , Lupus Erythematosus, Systemic/complications , Male , Microscopy, Electron , Middle Aged
6.
Am J Kidney Dis ; 20(2): 150-8, 1992 Aug.
Article in English | MEDLINE | ID: mdl-1496968

ABSTRACT

Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.


Subject(s)
Acute Kidney Injury/etiology , Antiphospholipid Syndrome/complications , Lupus Erythematosus, Systemic/complications , Renal Artery Obstruction/etiology , Thrombosis/etiology , Acute Kidney Injury/pathology , Adolescent , Adult , Antiphospholipid Syndrome/pathology , Biopsy , Female , Humans , Lupus Erythematosus, Systemic/pathology , Male , Renal Artery Obstruction/complications , Renal Artery Obstruction/pathology , Thrombosis/complications , Thrombosis/pathology
7.
Lupus ; 1(3): 187-9, 1992 May.
Article in English | MEDLINE | ID: mdl-1301980

ABSTRACT

Current management of primary or secondary antiphospholipid antibody (aPL) syndromes with known embolic phenomena requiring anticoagulation is empiric in the setting of elective orthopedic procedures. Short-term withdrawal of warfarin with continuance of aspirin and glucocorticoid therapy was undertaken for sequential bilateral knee replacements in a lupus patient with aPL. Her course was successfully managed without thrombo-embolic complications.


Subject(s)
Antibodies, Antiphospholipid/blood , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/surgery , Adult , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/drug therapy , Antiphospholipid Syndrome/immunology , Female , Humans , Knee Prosthesis/adverse effects , Lupus Erythematosus, Systemic/complications , Osteonecrosis/complications , Osteonecrosis/immunology , Osteonecrosis/surgery , Postoperative Complications/prevention & control , Thromboembolism/prevention & control
8.
J Okla State Med Assoc ; 85(2): 61-8, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1573472

ABSTRACT

Antibodies to negatively charged phospholipids (aPL) are associated with a wide clinical spectrum. Primarily the clinical problems present as localized and/or generalized thromboses, recurrent fetal loss, strokes, and various cytopenias. The clinical settings which would prompt the physician to consider aPL as causal or contributory to pathology in many organ systems are reviewed, and guidelines for screening and confirmatory testing are defined. Since effective treatments do exist to decrease or prevent morbidity, and in some cases, mortality, the generalist as well as the specialist should be aware of the many faces these primary and secondary syndromes present to them in daily practice.


Subject(s)
Antiphospholipid Syndrome , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/etiology , Antiphospholipid Syndrome/therapy , Clinical Protocols/standards , Enzyme-Linked Immunosorbent Assay , Humans , Mass Screening , Partial Thromboplastin Time , Research
9.
Ann Emerg Med ; 21(2): 207-11, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1739215

ABSTRACT

We present the case of a 26-year-old man with an exacerbation of apparent chronic asthma with chronic peripheral vascular disease due to recurrent venous thrombosis. Localized livedo reticularis, new cutaneous infarctions, severe venous insufficiency, thrombocytopenia, renal failure, and cerebral supratentorial dysfunction were noted. During hospital admission, antibodies to phospholipids in high titer were present by three different testing methods. Renal biopsy demonstrated significant renal vasculature abnormalities characteristic of hemolytic endovasculopathy, and magnetic resonance imaging showed multiple cerebral infarctions. This case exemplifies the spectrum of presentations and management of the primary antiphospholipid antibody syndrome. The clue to its presence in this patient was the livedo reticularis rash, a cutaneous marker for this syndrome that was evident in the emergency department.


Subject(s)
Antiphospholipid Syndrome/diagnosis , Dyspnea/etiology , Skin Diseases/etiology , Thrombophlebitis/etiology , Adult , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , Asthma/complications , Diagnostic Errors , Emergency Service, Hospital , Humans , Male , Recurrence , Skin/blood supply , Skin Diseases/diagnosis
12.
Semin Dermatol ; 10(3): 206-16, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1931570

ABSTRACT

Cutaneous manifestations of systemic connective tissue diseases, such as scleroderma and its variants, polymyositis, and dermatomyositis, often prompt early dermatologic consultation. Indirect immunofluorescent autoantibody determinations using tissue culture substrates are initial screening tests that are highly positive in the majority of patients with scleroderma and its variants, but are less frequently positive in patients with polymyositis and dermatomyositis. When combined with second-level analyses for the multiplicity of precipitin autoantibodies that have been defined in both these major classes of rheumatic diseases, most autoantibodies of both diagnostic and prognostic significance can be defined efficiently and cost-effectively. The major autoantibody specificities characteristic of these connective tissue diseases are summarized in this article, with emphasis on current concepts of their clinical molecular, and possible pathogenetic significance.


Subject(s)
Autoantibodies/analysis , Dermatomyositis/immunology , Myositis/immunology , Scleroderma, Systemic/immunology , Humans
13.
Clin Exp Rheumatol ; 5(4): 317-21, 1987.
Article in English | MEDLINE | ID: mdl-3326691

ABSTRACT

The relationship between anticentromere antibodies (ACA), antitopoisomerase I or Scleroderma 70 (Scl-70) antibodies, HLA-DR antigens, and clinical manifestations of scleroderma were examined in 51 patients defined by ARA criteria. No association between a given HLA-DR antigen and either ACA or anti-Scl-70 was found. Statistically significant associations were noted for patients with ACA who had a lower frequency of arthritis and longer disease duration; anti-Scl-70 patients were more likely to be males with a higher frequency of pulmonary, cardiac and sicca symptoms.


Subject(s)
Autoantibodies/analysis , HLA-D Antigens/analysis , HLA-DR Antigens/analysis , Scleroderma, Systemic/immunology , Adult , Aged , Antibodies, Antinuclear/analysis , Centromere/immunology , DNA Topoisomerases, Type I , Female , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Nuclear Proteins/immunology
14.
Med Clin North Am ; 70(2): 237-61, 1986 Mar.
Article in English | MEDLINE | ID: mdl-2419715

ABSTRACT

The use of tissue culture substrates for immunofluorescence determinations of nuclear, cytoplasmic, and mitotic cell-related autoantibodies has resulted in the delineation of diverse new specificities, whose clinical correlates are now becoming apparent. This review details both major and minor autoantibody specificities, the status of knowledge regarding their target antigens, and the relation of these serologic systems to distinctive rheumatic disease syndromes.


Subject(s)
Autoantibodies/analysis , Nuclear Proteins , RNA, Small Cytoplasmic , Rheumatic Diseases/diagnosis , Ribonucleoproteins, Small Nuclear , Antibody Specificity , Arthritis, Rheumatoid/immunology , Autoantigens/immunology , Cell Nucleolus/metabolism , Centromere/immunology , DNA/immunology , DNA Topoisomerases, Type I , DNA, Single-Stranded/immunology , Deoxyribonucleoproteins/immunology , Dermatomyositis/immunology , Fluorescent Antibody Technique , Histones/immunology , Humans , Lupus Erythematosus, Systemic/immunology , Mass Screening , Myositis/immunology , Nucleoproteins/immunology , Phospholipids/immunology , RNA/immunology , RNA/metabolism , Ribonucleoproteins/immunology , Scleroderma, Systemic/immunology , snRNP Core Proteins , SS-B Antigen
17.
Ann Allergy ; 55(3): 421-33, 1985 Sep.
Article in English | MEDLINE | ID: mdl-2412470

ABSTRACT

Guidelines have been presented for the optimal selection and interpretation of various laboratory tests related to rheumatologic, immunologic, and allergic disorders. The last decade has witnessed many technologic changes in the performance of screening tests for autoantibodies, and an expeditious approach to the detection of the clinically useful autoantibody system has been outlined. When both an immunofluorescent assay using an actively dividing substrate such as HEp-2 and an immunodiffusion test for precipitin autoantibodies are performed on patient sera, it is likely that most of the significant diagnostic and prognostic systems will be detected. Although exact pathogenetic roles have not been defined for all autoantibodies, it is apparent that highly specific markers for certain rheumatic diseases exist and the pertinent clinical aspects of each individual autoantibody-autoantigen system has been summarized. Why so many autoantibodies are cross-reactive with seemingly unrelated antigens is a perplexing aspect of autoimmunity, a disease process for which the necessary and sufficient conditions of development have not been defined even after decades of research. One recent hypothesis regarding the generation of diverse autoantibodies is the tenet that production is interrelated in an auto-anti-idiotypic network. Support for this hypothesis comes from the recent successful use of anti-idiotypes to DNA autoantibodies in an attempt to abrogate pathogenetic effects of target organ damage in murine models of SLE. A similar approach might be undertaken with some of the other autoantibody systems in an attempt at a novel therapy for disorders of immunoregulation.


Subject(s)
Clinical Laboratory Techniques/trends , Hypersensitivity/diagnosis , Immune System Diseases/diagnosis , Rheumatic Diseases/diagnosis , Animals , Antibodies, Antinuclear/analysis , Autoantibodies/analysis , Blood Sedimentation , C-Reactive Protein/analysis , Counterimmunoelectrophoresis , Creatine Kinase/metabolism , DNA/immunology , DNA, Single-Stranded/immunology , Dinitrobenzenes/immunology , Hemagglutination Tests , Histones/immunology , Humans , Immunodiffusion , Immunoglobulins/analysis , Mice , RNA/immunology , Rheumatoid Factor/analysis
19.
Med Clin North Am ; 69(3): 599-615, 1985 May.
Article in English | MEDLINE | ID: mdl-3892193

ABSTRACT

This article reviews the theoretical and clinical relationships among autoimmune, musculoskeletal, connective tissue syndromes, and various malignancies. The most common tumors encountered in clinical practice, and the syndromes with which patients present, are approached in terms of their direct or indirect relationship to the malignancies.


Subject(s)
Autoimmune Diseases/complications , Neoplasms/complications , Aged , Autoantibodies/analysis , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Connective Tissue Diseases/complications , Connective Tissue Diseases/immunology , Connective Tissue Diseases/pathology , Female , Humans , Male , Middle Aged , Muscular Diseases/complications , Muscular Diseases/immunology , Muscular Diseases/pathology , Neoplasms/immunology , Neoplasms/pathology , Rheumatic Diseases/complications , Rheumatic Diseases/immunology , Rheumatic Diseases/pathology
20.
Arthritis Rheum ; 27(7): 774-9, 1984 Jul.
Article in English | MEDLINE | ID: mdl-6378210

ABSTRACT

Routine examination of sera from patients with suspected or confirmed connective tissue disease has revealed the presence of autoantibodies directed against an unusual nuclear antigen. As characterized by immunofluorescence studies, the antigen is found exclusively in the nuclei of interphase cells, but appears to be part of the spindle pole in mitotic cells. Similar distributions in interphase and mitotic cells have been reported for the recently discovered nuclear mitotic apparatus (NuMA) protein. Using immunoblot analysis we have demonstrated that the autoantibodies that decorate the mitotic spindle poles are specific for the NuMA protein. Therefore, we conclude that the NuMA protein is a human autoantigen.


Subject(s)
Antigens/immunology , Autoantigens/immunology , Antibodies/immunology , Antibodies, Monoclonal/immunology , Fluorescent Antibody Technique , Humans , Immunologic Techniques , Molecular Weight , Peptide Fragments/immunology , Spindle Apparatus/immunology
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