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Biomedical subjects

W L Gross

Publications and source records attributed to W L Gross.

At least 19 recordsLinked to original sources
PubMed1992

Elevated serum levels of soluble interleukin-2 receptor in patients with Wegener's granulomatosis. Association with disease activity.

OBJECTIVE: To investigate whether soluble interleukin-2 receptor (sIL-2R), a marker of T cell activation, could be a useful marker of disease activity in Wegener's granulomatosis (WG). METHODS: Soluble IL-2R levels were determined by enzyme-linked immunosorbent assay. WG disease activity in 102 patients was assessed according to clinical features and levels of classic antineutrophil cytoplasmic antibody (c-ANCA) and C-reactive protein (CRP). RESULTS: Soluble IL-2R levels were higher in patients with generalized and active disease than in those with limited and inactive disease. In 25 patients with complete clinical remission, sIL-2R levels were significantly elevated, although levels of CRP and c-ANCA were normal. Eight of these 25 patients had disease relapses within 6 months. Levels of sIL-2R were significantly higher in patients who had relapses than in those who did not. Patients with clinically active WG but low c-ANCA or CRP levels had elevated levels of sIL-2R. CONCLUSION: Levels of sIL-2R correlate with disease activity in patients with WG, and may indicate imminent relapse.

Adult↗
PubMed1992

Mesna side effects which imitate vasculitis.

Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated with "low dose" CYC and prednisone for vasculitis developed severe side effects to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane lesions, and abdominal complaints with profuse diarrhea were noted approximately 3 weeks after the initiation of therapy for CYC-induced leukopenia and a conservatively reduced prednisone dosage. Positive reexposure tests confirmed the association to Mesna use, and hypersensitivity skin tests demonstrated a delayed hypersensitivity reaction.

Adult↗
PubMed1992

[The magnetic resonance tomographic signs of Wegener's granulomatosis in the head area].

MRI of the head was performed in 25 patients suffering from Wegener's granuloma. 23 patients showed evidence of mucosal thickening in the paranasal sinuses, the middle and inner ears and in the mastoid cells; these were characterised by low signal intensity of T1-weighted and high signal intensity of T2-weighted images. In 10 patients there were granulomas in the paranasal sinuses and in the orbits which showed low signal intensity of both T1-weighted and T2-weighted images. In 4 patients, additional images were obtained after the intravenous injection of Gd-DTPA. In 2 patients this resulted in non-homogeneous contrast accumulation in the granuloma. In 7 patients there were signal changes in the brain which were typical of infarcts. The complete extent of bone destruction in the facial skeleton was visible only by CT.

Adult↗
PubMed1992

[Orbital involvement in Wegener's granulomatosis].

BACKGROUND: Granulomas of the orbit can complicate Wegener's granulomatosis (WG). If they compress the optic nerve, blindness of one or both eyes may result. Therefore, early detection and sufficient treatment are important. MATERIAL AND METHODS: Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit and CNS were performed in patients suffering from WG and orbital granulomas (n = 6). The patients were seen interdisciplinary by internists, ENT-specialists, radiologists and ophthalmologists. RESULTS: 12 out of 121 biopsy proven WG-patients showed orbital granulomas during their disease process. Granulomas of the orbit could be best visualized by MRI. However, MRI and CT taken together were most informative. 6 patients with orbital granulomas are presented as case reports, in four of them WG lead to blindness of one eye. The course of orbital granulomas may be chronic progressive or acutely fulminant. Therapy of first choice is a high dosage, long-term immunosuppression with cyclophosphamide and prednisolone. CONCLUSIONS: The detection of orbital granulomas in WG is most successful using CT and MRI. In addition to that, the analysis of visual acuity and visual field are the most important parameters in the detection and follow-up of orbital granulomas. A high dosage, long-term immunosuppression is the treatment of first choice, but in rapidly progressive cases an early decompression of the orbit has to be discussed additionally.

Abscess↗
PubMed1992

Immunodiagnostic aspects of autoantibodies against myeloperoxidase.

The antigen specificity of autoantibodies causing perinuclear staining of granulocytes and monocytes (pANCA) was evaluated by analyzing 3000 sera, which were sent to us for screening of anticytoplasmic antibodies (ACPA, synonym: cANCA, anti-proteinase 3). In 620 sera, perinuclear staining was found. Antigen specificity was investigated by a myeloperoxidase ELISA and indirect immunofluorescence with Hep2 cells specific for antinuclear antibodies (ANA). Only 9.8% of the 620 sera showed reactivity with myeloperoxidase (AMPO), while 85.6% contained ANA which induced a pANCA-like staining. A further 4.6% of the 620 sera were neither ANA nor AMPO positive. Therefore, pANCA in general is only an indication that one should look for AMPO or other antilysosomal autoantibodies, when ANA have been excluded. To investigate the disease specificity of AMPO, we examined sera from patients with several well-defined autoimmune diseases. There were only very few positive results in collagen vascular diseases (3/114) (positive/total), primary systemic vasculitis (1/116) and clinically and histologically proven Wegener's granulomatosis (2/213). On the other hand, AMPO were present in patients with different forms of glomerulonephritis (45/192), especially crescentic glomerulonephritis (CGN) (34/79) without immune deposits in their biopsy specimen (3/30 showed trace deposits of IgM). There were, however, additionally 11 patients with symptoms resembling WG (who were cANCA negative, w/o characteristic WG biopsy), who had no obvious renal symptoms. These findings indicate that AMPO are primarily associated with idiopathic GN, especially CGN. Together with anti-proteinase-3 antibodies and anti-glomerular basement membrane antibodies they are an essential serologic parameter in the diagnosis of unclear systemic diseases with renal involvement.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

B-lymphocyte response in peripheral blood of patients with pulmonary sarcoidosis.

Sarcoidosis is a granulomatous disorder which can be characterized by various immunologic abnormalities including lymphocyte dysfunctions. The purpose of this study was to investigate the B-lymphocyte reactivity in the peripheral blood of 29 various patients with pulmonary sarcoidosis. A significant decrease in the production of IgG, IgM and IgA in supernatants of cultivated sarcoidosis B-cells both after stimulation with a T-cell dependent polyclonal B-cell activator (pokeweed mitogen) and with a T-cell independent polyclonal B-lymphocyte activator (Klebsiella pneumoniae) was seen, which suggested a disturbance in the B-cell differentiation of sarcoidosis patients. Those patients which were known to have a clinically active disease or a high intensity alveolitis in the bronchoalveolar lavage fluid showed a greater reduction in the B-cell differentiation response. Further evaluation of Ig-G subclasses displayed a significant decrease in the secretion of IgG1, IgG3 and IgG4. In contrast to the differentiation, the proliferation response of sarcoidotic peripheral blood lymphocytes to different mitogens did not differ from healthy controls.

Adult↗
PubMed1992

[Elevated serum levels of ICAM-1 in Wegener's granulomatosis].

Circulating soluble ICAM-1 (sICAM-1) isoforms are known to be elevated in inflammatory and autoimmune disorders (SLE, RA). A correlation between levels of circulating sICAM-1 and disease activity was described (5). In sera from 31 patients suffering from histologically confirmed Wegener's granulomatosis (WG) elevated levels of ICAM-1 were now detected in this primary systemic vasculitis. In generalized active disease circulating ICAM-1 levels were significantly higher when compared to remission and healthy control individuals. Sera from WG patients collected during intercurrent infections while on immunosuppressive drugs showed no elevation of circulating ICAM-1.

Antigens, CD↗
PubMed1992

[A new type of ANCA in sera of patients with ulcerative colitis: effects of therapy and disease severity on serum titer].

Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 control sera were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typically diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA) seen in active Wegener's granulomatosis (WG). Only 1 of the 44 sera from patients with Crohn's disease and none of the control sera showed positive p-ANCA reactions. Only 1 of the 64 CU sera was positive for antinuclear antibodies, and another one showed a positive reaction in the anti-proteinase-3 ELISA which is specific for WG. Antibodies against myeloperoxidase were negative in the CU sera. 31 out of the 37 p-ANCA-positive sera (84%) were obtained from patients with high disease activity. p-ANCA titers became negative after long-term steroid therapy and after complete colectomy. These preliminary data suggest that ANCA screening may be of value in differentiating IBD and in monitoring disease activity and drug effects in UC patients.

Adult↗
PubMed1991

A human renal cancer line as a new antigen source for the detection of antibodies to cytoplasmic and nuclear antigens in sera of patients with Wegener's granulomatosis.

Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (C-ANCA), have proved to be a useful clinical tool to support the diagnosis or to monitor disease activity in Wegener's granulomatosis (WG). Till now, human neutrophil granulocytes have represented the major antigen source used to detect antibodies in WG by the immunofluorescence technique (IFT). We have tested serum samples of 164 patients with different connective tissue diseases (50 suffering from clinically active WG) performing IFT on a human renal cancer line (SK-RC11) and have found antibodies against the nuclear and cytoplasmic antigens in 39 patients. C-ANCA+ sera displayed a characteristic diffuse cytoplasmic staining pattern. Antibody titers measured with human granulocytes were comparable to titers obtained using culture cells. Antibody binding could be inhibited by preabsorption with an extract of human granulocytes or purified proteinase 3. A protein of 29 kDa MW could be isolated by affinity purification using a SK-RC11 extract and a high-titer C-ANCA+ serum and antigenic identity was further confirmed by IFT using a monoclonal antibody to proteinase 3. Treatment of tumor cells with cytokines (interferon, tumor necrosis factor) led to a time dependent translocation of the antigen into the nucleus and back to the cytoplasm. The antigen was also expressed on the surface of live cells colocalized with MHC II. In addition, 21 WG patients had antibodies to cytoplasmic organelles identified by laser scanning microscopy as secretory vesicles of the Golgi complex, and five had antibodies to nuclear antigens. This is, to the best of our knowledge, the first report of proteinase 3 in human non-leukemic cells. Our data demonstrate, that the repertoire of antigens recognized by antibodies in WG sera is not limited to human neutrophils and monocytes and indicates a possible functional role of the antigenic proteins.

Antibodies, Antinuclear↗
PubMed1991

Antineutrophil cytoplasmic autoantibodies: immunobiological aspects.

Antineutrophil cytoplasmic autoantibodies (ANCA) specific for constituents of neutrophil primary granules and monocyte lysosomes have been demonstrated in various vasculitic disorders. The staining pattern in indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate allows distinction among 3 types of ANCA: 1) classic anti-neutrophil cytoplasmic antibody (cANCA, formerly known as ACPA); 2) a type with a perinuclear/nuclear staining pattern produced when alcohol-fixed neutrophils are used as substrate (pANCA); and 3) a mixture of both of the above types (xANCA, also described recently as pANCA). Most cANCA are directed against proteinase 3 ("Wegener's autoantigen"). Some pANCA have specificity for myeloperoxidase and are associated with idiopathic crescentic glomerulonephritis ("renal vasculitis") and other systemic vasculitides exhibiting a paucity of immune deposits in blood vessels. In addition to being a useful serological marker, ANCA appear to be directly involved in the pathogenesis of systemic vasculitis. ANCA can activate cytokine-primed granulocytes and monocytes to undergo a respiratory burst and degranulation. This effect leads to vasculitis through the attachment of these cells to the vascular endothelium primed by cytokine-induced expression of adhesion molecules (E-LAM 1) on the endothelium. Thus, the release of toxic oxygen radicals and lytic enzymes is capable of causing vascular damage. In the present paper we report on the main target antigens and on the history, nomenclature, laboratory methods, and etiopathological implication of ANCA. Additional pathophysiological aspects of ANCA and/or autoreactive T cells and immunoregulatory events are also discussed.

Autoantibodies↗
PubMed1991

[Tryptophan-induced fasciitis-scleroderma-eosinophilia syndrome].

A fasciitis-sclerodermia-eosinophilia syndrome developed in four female patients, aged between 55 and 75 years, after the ingestion of tryptophan, 1.5-6.0 g daily, for 13 months to 7 years. It began characteristically with hard oedema of the limbs, sometimes also of the trunk. Later there occurred diffuse indurations of the body surface with fixation of the skin to fascial planes. This was associated with mainly sensory peripheral neuropathy. Three of the patients had an eosinophilia (12-30%). Histological examination revealed a cell-poor fasciitis, fibrosis of the cutis and subcutis, perimyositis and epidermal atrophy of varying degree. Erythrocyte sedimentation rate was at most slightly increased. Antinuclear antibodies were demonstrated in one patient (1:80). Serum aldolase concentration was raised (3.4-5.4 U/l), while creatine kinase was normal. The disease progressed even after tryptophan was discontinued, in only one patient there was improvement during glucocorticoid treatment. In two cases the skin induration regressed slowly after administration of methotrexate (15 mg weekly) and hydroxychloroquine (400 mg daily).

Aged↗
PubMed1991

Antineutrophil cytoplasmic autoantibody-associated diseases: a rheumatologist's perspective.

Autoantibodies against neutrophil cytoplasmic antigens (ANCA) produce two major immunofluorescence (IF) patterns on ethanol-fixed granulocytes: the "classical" (centrally accentuated) C-ANCA, associated with Wegener's granulomatosis (WG), and P-ANCA (perinuclear), which mainly occur in renal vasculitis. Rheumatic manifestations are an important clinical finding in systemic vasculitis, often preceding a fulminant course and sometimes imitating various rheumatic disorders. We analyzed the incidence of ANCA in rheumatic patients and looked for the frequency of rheumatic symptoms in systemic vasculitis. In WG (n = 186), we found rheumatic symptoms in 55% (myalgia, 45%; arthritis, 21%); in 90%, rheumatic complaints were associated with active vasculitis. In 730 patients with various rheumatic conditions (eg, 268 rheumatoid arthritis, 130 systemic lupus erythematosis [SLE], 32 sharp-S, 50 ankylosing spondylitis, 43 systemic sclerosis) no C-ANCA were found. On the contrary, the P-ANCA pattern was seen in seven of 62 giant cell arteritis, five of 27 Felty's/Still's syndrome, and four of 130 SLE patients in addition to renal vasculitis (21/74). We demonstrated that 95% of C-ANCA-positive sera react with proteinase 3 (PR3 or myeloblastin). Using monoclonal antibodies, we showed that PR3 is expressed on the plasma membrane of neutrophil granulocytes and monocytes; thus, PR3 autoantigens are accessible for circulating antibodies. The detection of ANCA in sera from vasculitis and other rheumatic diseases is of immunodiagnostic value and provides new insight in the pathogenesis of systemic vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗