Hydroxychloroquine treatment for primary Sjögren's syndrome: a two year double blind crossover trial.

Objectives: In 1985 and 1988 a positive effect of treatment of primary Sjögren's syndrome with hydroxychloroquine was reported in two small open studies. To investigate further the clinical and laboratory effects of hydroxychloroquine in primary Sjögren's syndrome a two year study was performed.

Methods: The design of the study included a prospective, placebo controlled, two year double blind crossover trial in 19 patients.

Antimyeloperoxidase-associated proliferative glomerulonephritis: an animal model.

To develop an animal model for antimyeloperoxidase (MPO)-associated necrotizing crescentic glomerulonephritis (NCGN), we immunized Brown Norway rats with MPO and localized a neutrophil lysosomal enzyme extract, primarily consisting of MPO and elastinolytic enzymes, plus H2O2, the substrate of MPO, to the glomerular basement membrane (GBM). Upon immunization rats developed antibodies and positive skin tests to MPO. After unilateral perfusion of the left kidney with the lysosomal enzyme extract and H2O2, MPO and immunoglobulin (Ig)G localized transiently along the GMB.

Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases.

To evaluate the diagnostic significance of neutrophil cytoplasmic antibodies in chronic liver diseases, we assessed the prevalence of neutrophil cytoplasmic antibodies in autoimmune liver diseases, in particular in primary sclerosing cholangitis, autoimmune chronic active hepatitis and primary biliary cirrhosis, and we also determined the specificity of perinuclear-pattern neutrophil cytoplasmic antibodies for these autoimmune liver diseases by testing sera from patients with nonautoimmune chronic liver diseases. Neutrophil cytoplasmic antibodies were detected in 79% of sera from patients with primary sclerosing cholangitis (n = 24), in 88% of sera from patients with autoimmune chronic active hepatitis (n = 24) and in 28% of sera from patients with primary biliary cirrhosis (n = 25). The presence of neutrophil cytoplasmic antibodies in these diseases correlated significantly (p < 0.

Serum markers of T cell activation in relapses of Wegener's granulomatosis.

Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml) 6 months before the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P = 0.10).

Occurrence of autoantibodies to human leucocyte elastase in Wegener's granulomatosis and other inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCAs) constitute a new class of autoantibodies that seem to recognise myeloid lysosomal enzymes. The occurrence of ANCAs with specificity for human leucocyte elastase (HLE) was assessed in serum samples that were routinely submitted for ANCA determination. During a study period of more than six years anti-HLE was found in only six out of 1102 serum samples that produced a perinuclear or an atypical cytoplasmic staining pattern on ethanol fixed granulocytes.

Anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease.

ANCA were detected in 67% of sera from patients with primary sclerosing cholangitis (n = 15), in 83% of sera from patients with autoimmune chronic active hepatitis (n = 18) and in 35% of sera from patients with primary biliary cirrhosis (n = 20). ANCA were not detected in non-autoimmune chronic liver diseases. Characterization studies of the antigens involved showed that ANCA in autoimmune liver disease are not directed against myeloperoxidase (mpo), proteinase 3 (pr3) or elastase (hle), but the ANCA in autoimmune liver disease show reactivity with lactoferrin, a 67/66 kD protein combination or a 63/54 kD protein combination on Western Blots.

Antineutrophil antibodies in inflammatory bowel disease recognize different antigens.

Anti-neutrophil cytoplasmic antibodies (ANCA) were observed in 31 out of 68 sera (45%) from Ulcerative Colitis (UC) patients and in 13 out of 38 Crohn's Disease (CD) sera (34%). The presence of ANCA was not related to disease activity, nor to the localization of the disease manifestations. By Western Blotting ANCA showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD MW, or polypeptides occurring as a doublet of 63/54 kD MW.

Serum markers of T-cell activation in relapses of Wegener's granulomatosis.

Levels of soluble IL-2 receptor (sIL-2R), soluble CD4 (sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T-cell activation in serial serum samples drawn monthly from 16 patients showing 18 histologically proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1162 U/ml (median, 95% CI 843 to 1814 U/ml) at three months before the relapse to 1684 U/ml (95% CI 1254 to 2202 U/ml) at the time of relapse for the whole group (P = 0.10).

Anti-neutrophil cytoplasmic antibodies in giant cell arteritis and polymyalgia rheumatica.

Antineutrophil cytoplasmic antibodies (ANCA) were demonstrated in all sera from 11 patients with active giant cell arteritis (GCA) using indirect immunofluorescence on 9% paraformaldehyde(PF)-fixed neutrophils according to Pryzwanski (median titer 1:256, range 1:64 to 1:512). After treatment during inactive disease titers decreased in all sera. Eight out of 9 sera from patients with active polymyalgia rheumatica (PMR) produced a cytoplasmic staining on Pryzwanski-fixed neutrophils in low titers (median titer 1:16, range 0 to 1:32), as did 8 out of 25 sera from healthy blood donors.

Perinuclear antineutrophil cytoplasmic antibodies (p-ANCA): clinical significance and relation to antibodies against myeloid lysosomal enzymes.

In a prospective study of 27 months duration p-ANCA were found in 120 patients. 35% of these patients had vasculitis and/or glomerulonephritis. 28% of the p-ANCA positive sera reacted with myeloid lysosomal enzymes.

Induction of an humoral and cellular (auto) immune response to human and rat myeloperoxidase(MPO) in Brown-Norway(BN), Lewis and Wistar Kyoto(WKY) rat strains.

Anti-MPO and anti-proteinase 3 antibodies are strongly associated with certain forms of vasculitis and glomerulonephritis and a pathophysiological role for the antibodies has been hypothesized (Kallenberg et al. 1991). To test this hypothesis WKY, Lewis and BN rats were immunized with human MPO.

Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis.

Pulmonary function in systemic lupus erythematosus is related to distinct clinical, serologic, and nailfold capillary patterns.

Purpose: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serologic, and nailfold capillary patterns overlapping scleroderma.

Patients And Methods: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serologic studies directed at the antigenic specificities of antinuclear antibodies were performed.

Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.

Many patients presenting with symptoms suggestive of a connective tissue disease do not fulfill criteria for a specific connective tissue disease at initial presentation. Some of these patients with undifferentiated connective tissue disease eventually develop a specific connective tissue disease. Recently, a large cohort of 213 patients from different centers with undifferentiated connective tissue disease of early onset were enrolled in a prospective protocoled study.

Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity?

To investigate the possible role of IL-6 in the activation of the autoimmune process in systemic lupus erythematosus (SLE), we serially measured concentrations of IL-6, IgG, and anti-dsDNA antibodies before and during exacerbations in patients with SLE. In addition, we serially related the IL-6 response to the generation of the acute phase reactant C-reactive protein (CRP). Sixteen consecutive patients who developed an exacerbation were analysed in this study.

Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin.

Three patients with lupus with severe auto-immune thrombocytopenia were treated with high doses of intravenous gammaglobulin. In the patient with active disease a prolonged but partial response with respect to platelet counts was observed. In the two other patients who had no disease activity other than thrombocytopenia at the time of intravenous gammaglobulin treatment a minor (and only transient) increase in platelet counts was seen after treatment.

Patients with systemic lupus erythematosus and Jaccoud's arthropathy: a clinical subset with an increased C reactive protein response?

Jaccoud's arthropathy is a chronic deforming synovitis occurring in a subset of patients with systemic lupus erythematosus (SLE). To evaluate whether patients with SLE and Jaccoud's arthropathy behave differently in their acute phase reaction from patients with SLE without Jaccoud's arthropathy, a prospective study was carried out on 72 consecutive patients with SLE. Patients were assessed for Jaccoud's arthropathy according to a protocol, disease activity was scored, and laboratory tests, including tests for C reactive protein, were performed.

Raynaud's phenomenon as an early sign of connective tissue diseases.

Raynaud's phenomenon (RP) is seen in 5-10% of the population and generally follows an indolent course. In some cases it may be the first sign of a connective tissue disease (CTD). In patients referred to the clinician because of their RP, obviously the more severe cases, CTD, in particular scleroderma, will develop, however, in a considerable percentage.

Influence of ageing on antibody formation in vivo after immunisation with the primary T-cell dependent antigen Helix pomatia haemocyanin.

The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a dose of HPH which could be used to discriminate between the responsiveness of healthy and immunocompromised individuals, we first established a dose-response curve for this antigen in 60 healthy young volunteers.