A novel assay for neutrophil clustering activity of human sera: relation to disease activity and neutropenia in systemic lupus erythematosus.

A simple and reproducible method for the measurement of serum neutrophil clustering activity was developed. High clustering activity was found in 19/30 patients with active systemic lupus erythematosus (SLE), and 14/20 of those with severe disease flares. In contrast, 0/10 patients with quiescent SLE and 2/20 patients with rheumatoid arthritis had high neutrophil clustering activity. Particularly high clustering activity was found in patients with SLE with lupus glomerulonephritis and in certain patients with central nervous system disease. An inverse correlation was found between neutrophil clustering activity and peripheral blood neutrophil count in patients with SLE not treated with glucocorticoids, and clustering activity was high in all patients with low neutrophil counts in this group. A moderate correlation was found between neutrophil clustering activity and C1q binding circulating immune complexes. Non-steroidal anti-inflammatory drugs and glucocorticoids had little direct effect on neutrophil clustering activity.     

Elevated plasma interleukin-6 in patient with idiopathic thrombocytopenic purpura

Plasma Interleukin-6 (IL-6) level was measured in patients with idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), rheumatoid arthritis and aplastic anemia. Increase in the plasma level of IL-6 was observed in patients with ITP and SLE. The plasma IL-6 level decreased with progression of the treatment for ITP, and it showed weak negative correlations with the platelet count at the onset of ITP. The increases in the plasma IL-6 level suggest the involvement of activation of the immune system in the pathogenesis of ITP.     

Rheumatoid factor in rheumatoid arthritis associated renal disease and in lupus nephritis.

To test the hypothesis that rheumatoid factor (RF) protects against (immune complex mediated) renal disease, patients with rheumatoid arthritis (RA; 48 with nephropathy of various types, 35 without renal disease) and systemic lupus erythematosus (SLE; 35 with and 17 without nephritis) were evaluated for the presence and titre of RF. There was no correlation between RF and nephropathy in RA, whereas in SLE RFs were almost exclusively seen in patients without nephropathy. This result supports the above hypothesis for lupus nephropathy but not for RA associated renal disease, and it may be explained by a more pronounced role for immune complexes in SLE and interference of RFs with the complexes.     

The CD14+ CD16+ monocyte subset in rheumatoid arthritis and systemic lupus erythematosus

Most human peripheral blood monocytes strongly express surface CD14, but not CD16 (CD14+ +/CD 16-). A smaller group of monocytes express lower levels of CD14 and also express CD16 (CD14+/CD16+). This subgroup has different functional characteristics and is expanded in a number of disease states. We aimed to determine the percentage of circulating CD14+ /CD16+ monocytes in rheumatoid arthritis and systemic lupus erythematosus (SLE) and relate this to disease measures. Peripheral blood was sampled from 31 SLE patients, 19 rheumatoid arthritis patients, and 19 healthy controls. The percentage of CD14+/CD16+ monocytes was determined by immunofluorescence labelling and dual colour flow cytometry. The percentage of CD14+/CD16+ monocytes was significantly lower in rheumatoid arthritis (median 4.90%) than in normal subjects (median 7.30%, P = 0.014), and in rheumatoid arthritis than in SLE patients (median 9.40%, P = 0.009). The percentage of CD14+/CD16+ monocytes in SLE was not significantly different from that in healthy subjects. This lower percentage of CD14+/CD16+ monocytes in rheumatoid arthritis may be important in the pathogenesis of this disease.     

Multiple coronary aneurysms and acute myocardial infarction in a female patient with rhupus: case report and literature review

Clinical Rheumatology - Coronary artery aneurysms (CAA) are an infrequent cause of coronary artery disease in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), most occurring...     

Neutrophil aggregation induced by sera from patients with active systemic lupus erythematosus

Activated complement components and immune complexes cause neutrophil (PMN) aggregation in vitro and in vivo, as in dialysis-induced neutropenia and adult respiratory distress syndrome. To investigate the possible role of PMN aggregation in systemic lupus erythematosus (SLE), we studied the capacity of 59 sera from 53 patients to induce aggregation of normal PMN in vitro. Neutrophil aggregating activity (NAA) was present in the sera of 26 of 28 patients with active SLE. The mean NAA in this group was significantly greater than that found in 13 patients with inactive SLE, 20 patients with rheumatoid arthritis, and 17 normal controls. In patients with SLE there was a positive correlation between disease severity and the quantitative measure of NAA. NAA did not correlate with serum C3 or C4 nor with the presence or absence of circulating immune complexes. High levels of NAA were particularly characteristic of central nervous system lupus. These data suggest that the formation of intravascular leukoaggregates may contribute to morbidity in SLE.     

Platelets as target cells in rheumatoid arthritis and systemic lupus erythematosus: A platelet specific immunoglobulin inducing the release reaction

Summary Sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were assessed for in vitro platelet activation as measured by serotonin release; 24% (30) of 124 tested RA sera and 51% (35) of 69 SLE sera induced a significant 3H serotonin release. Investigation of 17 synovial fluid samples from RA patients revealed significant release in 82%. Concomitant testing for lymphocytotoxic antibodies and immune complexes did not show any correlation to platelet activation. Upon gel filtration the release-inducing activity of positive sera was localized in the region of 160 000 Daltons. Further characterization by ion exchange chromatography, immune electrophoresis, chromatographic and SDS PAGE molecular weight determinations, as well as analytical ultracentrifugation all confirmed the IgG nature of the release-inducing protein. Negative blocking experiments performed by preincubation of platelets with Fc-IgG fragments prior to challenge with a release-inducing serum excluded the participation of Fc receptors in the reaction. It was concluded that the release was caused by a platelet reactive IgG antibody. This antibody may also cause release of platelet mediators in vivo and may thus contribute to the pathogenesis of the generalized vasculopathy in both diseases.     

Thyroid disease in systemic lupus erythematosus and rheumatoid arthritis

SIR, We determined the degree of overlap between autoimmunethyroid disease and two non-organ-specific autoimmune diseases,systemic lupus erythematosus (SLE) and rheumatoid arthritis(RA). Both SLE and RA are commonly encountered in our out-patientpractice and were chosen because of their clinical relevance. Sixty-nine SLE and 64 RA patients fulfilling the American RheumatismAssociation criteria for SLE [1] and RA [2] were selected forthis study. Patients from both groups were found     

Serum leucine aminopeptidase as an activity indicator in systemic lupus erythematosus: a study of 46 consecutive cases.

OBJECTIVE: To determine whether elevations in serum leucine aminopeptidase (LAP) levels reflected the underlying evolution of active disease in systemic lupus erythematosus (SLE). METHODS: We studied serum LAP levels, other laboratory indicators, and SLE Disease Activity Index (SLEDAI) scores, in 46 consecutive patients with SLE admitted to Tokyo Metropolitan Komagome Hospital. LAP levels in 46 patients with rheumatoid arthritis were also measured. RESULTS: Thirty-three SLE patients had elevated LAP levels. LAP levels correlated positively with levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase, and negatively with the total serum haemolytic complement and leucocyte, neutrophil and lymphocyte counts, but showed no correlation with alkaline phosphatase, gamma-globulin, beta2-microglobulin or C-reactive protein levels, or platelet count. The SLEDAI score correlated positively with LAP levels. The LAP level in patients with rheumatoid arthritis was near normal. CONCLUSION: The serum LAP level may be a potential activity indicator for SLE.     

The central role of dendritic cells and interferon-alpha in SLE

PURPOSE OF REVIEW: Until recently, systemic lupus erythematosus has been viewed mainly as a B-cell disease resulting from altered T cell-B cell interactions. The recognition of the fundamental role of dendritic cells in the control of tolerance and immunity led to the hypothesis that systemic lupus erythematosus may be driven through unabated dendritic cell activation. This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-alpha, in the pathophysiology of systemic lupus erythematosus. RECENT FINDINGS: CD14+ monocytes isolated from the blood of patients with systemic lupus erythematosus, but not those from healthy individuals, act as dendritic cells. Their activation is driven by circulating interferon-alpha that may come from one of the dendritic cell subsets (ie, plasmacytoid dendritic cells that infiltrate systemic lupus erythematosus skin lesions). Although only a fraction of patients with active systemic lupus erythematosus show circulating interferon-alpha, blood mononuclear cells from all of them display an interferon-alpha signature. SUMMARY: The disease model that the authors propose places interferon-alpha at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-alpha and/or interferon-alpha-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.     

Histone antibodies in systemic lupus erythematosus. A possible diagnostic tool

Antibodies to total histones and histone fractions H1, H2a-H4, H2b, and H3 were measured in serum samples from 61 patients with systemic lupus erythematosus (SLE), 33 with rheumatoid arthritis, 17 with systemic sclerosis, and 20 with various other diseases by use of a sensitive immunoenzymatic assay. Histone antibodies were present in 52.4% of the SLE samples whereas only 1 of the samples from other diseases was positive (systemic sclerosis). The presence of these antibodies in SLE patients was not associated with any specific clinical manifestations, but was correlated with activity of the disease: 87% (20 of 23) of patients with active SLE, in particular 9 of 9 not yet treated, showed histone antibody whereas only 18% (4 of 22) of samples from patients with inactive SLE were positive. We believe that the measurement of histone antibodies would be a useful addition to the present laboratory parameters (antinuclear and double-stranded DNA antibodies and circulating immune complexes) for the diagnosis and progression of systemic lupus erythematosus, particularly since they seem to appear during or just before the onset of an active phase and tend to be absent during remission.     

Rheumatoid factor isotypes and renal disease in systemic lupus erythematosus

There is no agreement on whether rheumatoid factor (RF) exerts protection, injury, or is an epiphenomenon with regard to kidney disease in systemic lupus erythematosus (SLE). In this study we examined the occurrence and isotype distribution of rheumatoid factor in SLE in relation to some clinical parameters, including renal function and arthritis. A highly significant correlation (p less than 0.001) was noted between the presence of IgG RF and absence of kidney disease. The IgG RF also seemed to protect SLE patients from developing arthritis (p less than 0.01). On the other hand, elevated IgM RF levels indicated active SLE disease. The results obtained are discussed in relation to the ability of RF to interact with immune complexes in vitro and in vivo.     

Decreased platelet serotonin levels in systemic lupus erythematosus

Platelet serotonin levels were measured in 41 patients with systemic lupus erythematosus (SLE) and 36 normal controls. SLE patients had significantly lower mean serotonin levels (243 +/- 131 versus 414 +/- 175 ng/10(9) platelets, P less than 0.001); the lowest levels occurred in those patients with active disease. No differences in mean platelet serotonin levels were found when we compared patients with or without a history of renal disease, thrombocytopenia, or neuropsychiatric involvement. Decreased release of platelet granule constituents, as measured by plasma levels of the alpha-granule protein, beta-thromboglobulin.     

The frequency of circulating immune complexes in rheumatoid arthritis and systemic lupus erythematosus

Summary Sera from patients with rheumatoid arthritis and systemic lupus erythematosus have been examined for the presence of complement-fixing immune complexes using three assays, (a) a fluid phase Clq binding assay, (b) a solid phase Clq binding assay and (c) the Raji cell assay.By simultaneously screening all the sera within each disease group we established that circulating immune complexes frequently occur but that there is a discordance between the assays, even between the two assays involving binding to Clq. Distinct clinical profiles emerged with the fluid phase Clq binding assay being most frequently positive in sera from patients with extra-articular rheumatoid arthritis. The solid phase Clq binding assay and the Raji cell assay were more frequently positive in sera from patients with systemic lupus erythematosus. The prevalence of circulating immune complexes and the comparative performance of the three assays in each disease is examined in detail.     

Studies of a common idiotype PR4 in autoimmune rheumatic disease

A new common idiotype, designated PR4, is described. This idiotype was originally identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy, which binds the major Mycobacterium leprae-derived antigen, phenolic glycolipid-1, poly(ADP)-ribose, DNA, and poly(dT). The PR4 idiotype was found in patients with systemic lupus erythematosus (SLE) (70%), rheumatoid arthritis (40%), and Sj?gren's syndrome (15%). It was not, however, found in the spouses of the SLE patients or (unlike other lupus idiotypes) in their healthy first-degree relatives. Although no correlation between PR4 idiotype levels and disease activity in SLE was found, a subset of rheumatoid arthritis patients with high levels of the idiotype was identified.     

Perforation of nasal septum in rheumatic diseases.

Perforation of the nasal septum was noted in 12 patients with rheumatic disease, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). Biopsies were taken from the rim of the perforation in 7 of the 12 and revealed no vasculitis, immunoglobulin deposition, or consistent abnormality. Nasal septal perforation is an occasional finding in rheumatic disease and the cause is unknown.     

A meta-analysis of structural MRI studies of the brain in systemic lupus erythematosus (SLE)

Clinical Rheumatology - A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis...     

Penicillamine associated pulmonary hemorrhage

Penicillamine is the drug of choice in Wilson's disease and a therapeutic alternative in rheumatoid arthritis. Autoimmune complications associated with penicillamine include cases resembling systemic lupus erythematosus and Goodpasture's syndrome. We report a case of diffuse pulmonary hemorrhage associated with prolonged penicillamine use in a patient with Wilson's disease with evidence of circulating immune complexes and complement activation, but without serologic or morphologic evidence of systemic lupus erythematosus, Goodpasture's syndrome or renal disease.     

Coffee consumption and the risk of rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization study

Clinical Rheumatology - We aimed to analyze the causal association between coffee consumption and the risk of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We performed a...     

Perforation of nasal septum in rheumatic diseases

Perforation of the nasal septum was noted in 12 patients with rheumatic disease, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), and mixed connective tissue disease (MCTD). Biopsies were taken from the rim of the perforation in 7 of the 12 and revealed no vasculitis, immunoglobulin deposition, or consistent abnormality. Nasal septal perforation is an occassional finding in rheumatic disease and the cause is unknown.