Reticuloendothelial system Fc receptor function in the drug induced lupus erythematosus syndrome.

In view of reported delayed clearance of 51Cr labelled IgG sensitized autologous erythrocytes in systemic lupus erythematosus, we measured clearance half-time (t1/2) in 16 patients with the drug induced lupus erythematosus syndrome. The mean t1/2 for the patients with drug induced lupus was 52 min, and for 16 normals mean was 48 min, a difference without statistical significance. Nine of the patients with drug induced lupus had laboratory abnormalities only, and mean t1/2 in this group was not significantly different from that in the 7 symptomatic patients. T1/2 was not significantly associated with Clq or DNA binding levels in symptomatic or asymptomatic patients. Normal mean clearance of model immune complexes was thus present in patients with drug induced lupus, with and without symptoms, and may protect against renal and central nervous system disease in drug induced lupus erythematosus.

Visual evoked potentials altered by serum IgG of patients with multiple sclerosis.

Immunoglobulin G, isolated from serum of patients with multiple sclerosis was repeatedly injected into guinea pigs and serial visual evoked potentials were recorded. Latency changes indicated a reversible delay in conduction velocity in the central visual pathways. This finding suggests that some component of immunoglobulin plays a role in the pathogenesis of multiple sclerosis.

Reticuloendothelial system fc receptor function in rheumatoid arthritis.

Patients with systemic lupus erythematosus (SLE) have abnormal reticuloendothelial system (RES) IgG Fc receptor function which is correlated with disease activity and levels of immune complexes (IC). We studied RES function, IC levels, clinical and laboratory manifestations in 43 patients with RA. The articular index was abnormal in 42 patients (range of 6 to 153). Thirty were seropositive; 31 had an elevated erythrocyte sedimentation rate. Extraarticular manifestations included nodules (25), anemia (19), Sjögren's syndrome (6), vasculitis (4), and Felty's syndrome (2). Medication included corticosteroids (32), nonsteroidal antiinflammatory drugs (33), slow acting antirheumatic drugs (18), and cytotoxics (2). Thirty-three patients had IC (30 by the Clq binding assay, 21 by the Raji cell assay); 13 patients had normal RES function (t 1/2-24-60 min; upper 95% confidence limit in normals = 62 min). Thirty had prolonged clearance times (65-210 min, mean 106 min). In contrast to SLE, clearance times were not found to be correlated with IC levels, or clinical or laboratory measures of disease activity. Defective RES immune clearance may not be an important determinant in the pathogenesis of immunologic tissue damage in rheumatoid arthritis.

NIH Conference: Immunoglobulin G Fc receptor-mediated clearance in autoimmune diseases.

The reticuloendothelial system is thought to play an important role in removing immune complexes and other immunologically active substances from the circulation via interaction with specific cell-surface receptors. The function of the reticuloendothelial system in humans with autoimmune diseases was studied in vivo by measuring the rate of removal of IgG-coated, radio-labeled autologous erythrocytes. Such cells are removed by phagocytic cells of the spleen, and the process depends on the presence of an intact IgG Fc fragment. Studies in patients with active systemic lupus erythematosus show a profound defect in Fc-receptor-specific clearance that correlates with disease activity. Patients with other autoimmune diseases have defects in Fc receptor functional activity when their illness is characterized by tissue deposition of immune complexes. Normal patients with HLA-B8/DRw3, an HLA type associated with an increased incidence of autoimmune disease, also have an increased incidence of defective Fc receptor-specific functional activity, suggesting that this defect may predispose patients with this haplotype to develop manifestations of immune complex-mediated disease.

Immunoresponsiveness in acute babesiosis in humans.

Immunoresponsiveness in patients with acute babesiosis was characterized. Lymphocyte subpopulations, mononuclear cell responses to nonspecific mitogens, and serum immunochemical values were studied in patients during acute babesiosis and after recovery (four to 40 months), controls, and seropositive individuals. Serum studies were also carried out retrospectively on stored sera from patients with babesiosis. Mean and differential lymphocyte counts and percentages of B lymphocytes were higher than in controls in patients with acute babesiosis, and levels of T lymphocytes bearing the IgG Fc receptor (T gamma) were significantly (P less than 0.01) elevated. Responses to nonspecific mitogens were suppressed during acute babesiosis. Levels of serum IgG and IgM and Clq binding were significantly increased whereas C3 and C4 levels and hemolytic activity were suppressed in acute-phase sera. The apparent paradox of an increased T suppressor/cytotoxic population in the presence of evidence of increased in vivo lymphocyte function is discussed in terms of the heterogeneity of the T gamma subpopulation.

A serial study of splenic reticuloendothelial system Fc receptor functional activity in systemic lupus erythematosus.

A serial study of reticuloendothelial system splenic Fc receptor function was undertaken in 13 patients with systemic lupus erythematosus (SLE). Fc receptor function was assessed by measuring the clearance half times of IgG-sensitized 51Cr-labeled autologous erythrocytes from the circulation. Prolonged clearance half times were initially detected in all patients, and the magnitude of the clearance defect was significantly correlated with disease activity (P less than 0.01, Spearman rank correlation) and immune complex levels (P less than 0.01). Clinical course and changes in receptor functional activity over time were found to be significantly correlated. Clearance half-times tended to return to normal in all 11 patients who clinically improved. The clearance half-time remained unchanged in 1 patient whose disease activity was stable, and it worsened in 1 patient whose illness flared. Levels of immune complexes also changed concordantly with clearance half-times and disease activity. These studies underscore the interrelationship between the presence of circulating immune complexes, defects in Fc receptor function that might lead to prolonged circulation of these complexes, and disease activity in SLE.

Inheritance of mixed cryoglobulinemia.

This paper describes a family in which 10 members of 3 generations have IgM-IgG cryoglobulinemia. Their pedigree is characteristic of autosomal dominant inheritance. No underlying disease that could account for the cryoglobulinemia has been identified in any patient, and no linkage of the cryoglobulinemia to HLA-A and -B locus haplotypes, blood group antigens, or immunoglobulin Gm allotypes has been detected. The rheumatoid factors of this kindred react with some, but not all, human IgG; however, their rheumatoid factors are not antibodies to any known human Gm or Km allotype. This family demonstrates that "essential" mixed cryoglobulinemia can be inherited, and that the clinical manifestations of an inherited cryoglobulinemia may vary among family members.

Reticuloendothelial system Fc receptor function and plasmapheresis in systemic lupus erythematosus: a preliminary report.

Reticuloendothelial System (RES) Fc receptor-mediated immune clearance and levels of immune complexes were measured in patients with systemic lupus erythematosus undergoing plasmapheresis. RES clearance defects improved and disease manifestations and levels of circulating immune complexes decreased after plasmapheresis. Patients with initially abnormal reticuloendothelial system function, elevated levels of circulating immune complexes, and active acute illness appeared to respond to plasmapheresis. One patient with normal immune clearance, lacking measureable immune complexes, and manifesting chronic disease remained unchanged. Improvements seen following plasmapheresis were best maintained in patients receiving parenteral cyclophosphamide in the post-pheresis period. The correlation of clinical response, improved RES function, and decreased levels of immune complexes suggests the interaction of the latter two parameters in disease pathogenesis. Plasmapheresis has an important role as a research tool, and may be of clinical usefulness in a small number of patients with serious complications of systemic lupus erythematosus.

Opsonic requirements for intravascular clearance after splenectomy.

We investigated the opsonic requirements for intravascular clearance of pneumococci in guinea pigs and of sensitized erythrocytes in human beings after splenectomy. The impaired clearance of injected pneumococci in splenectomized guinea pigs was corrected by immunization. This improvement in clearance was due to increased hepatic sequestration of organisms. There was a significant delay in antibody-mediated clearance of autologous erythrocytes sensitized with IgG (P < 0.001), although the rate of complement-mediated clearance in splenectomized patients was normal. A fourfold increase in sensitizing antibody resulted in a significant improvement in clearance that was due to increased hepatic sequestration (P < 0.005). One patient who had an intact spleen and who had previously received Thorotrast (thorium oxide) had impaired antibody-mediated clearance despite increased sensitization. These observations suggest that, after splenectomy the remaining macrophages of the reticuloendothelial system require increased amounts of antibody to mediate efficient intravascular clearance of opsonized particles.

Defective Fc-receptor functions associated with the HLA-B8/DRw3 haplotype: studies in patients with dermatitis herpetiformis and normal subjects.

Dermatitis herpetiformis is associated with the HLA-B8/DRw3 haplotype in over 90 per cent of patients, and various percentages have been reported to have circulating immune complexes. Since removal of immune complexes from the circulation is thought to depend on the Fc-receptor function of tissue macrophages, we studied this function by measuring the clearance of IgG-sensitized autologous erythrocytes in 16 patients with dermatitis herpetiformis, in normal controls with the HLA-B8/DRw3 haplotype, and in randomly selected controls. All patients were HLA-B8 positive, and all of 12 patients tested were HLA-DRw3 positive. Erythrocyte clearance was reduced in eight of the 16 patients, but did not correlate with immune-complex levels. Four of eight controls with HLA-B8/DRw3 also had delayed Fc-receptor-mediated clearance as compared with normal controls. In addition, both patients and HLA-B8/DRw3-positive controls had decreased percentages and total numbers of T cells bearing Fc receptors for IgG. These findings indicate a functional Fc-receptor defect associated with the HLA-B8/DRw3 antigens.

Sjögren's syndrome (Sicca syndrome): current issues.

This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjögren's syndrome alone (primary) and Sjögren's syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjögren's syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.

Sjögren's syndrome: a defect in reticuloendothelial system Fc-receptor-specific clearance.

To determine the functional status of reticuloendothelial system Fc receptors in patients with Sjögren's syndrome, we studied the rate of clearance from the circulation of 51Cr-labeled IgG-sensitized autologous erythrocytes in 19 patients. Fc-receptor-mediated clearance was abnormal in 12 of the 19 patients, with half-lives ranging from 80 to 356 min. There was a significant correlation between clearance rates and clinical manifestations of disease. Clearance rates tended to be normal in patients with disease limited to exocrine glands and abnormal in patients with widespread disease. In contrast, there were no correlations between the rate of clearance of IgG-sensitized erythrocytes and serum immune complex levels, serum complement component levels, or rheumatoid factor titers. The striking correlation between clearance rates and disease manifestations suggests that decreased clearance of immune complexes by defective reticuloendothelial system Fc receptors may contribute to disease pathogenesis.

Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus.

To determine whether reticuloendothelial-system immunospecific Fc-receptor function is abnormal in patients with systemic lupus erythematosus, we studied the clearance of IgG-sensitized 51Cr-labeled erythrocytes by these splenic macrophage membrane receptors in 15 untreated patients. Fc-specific clearance rates were strikingly abnormal in 13 of 15 patients (half-times ranging from 80 to 2256 minutes, P less than 0.001 as compared to controls). Abnormal clearances correlated with immune-complex levels (as measured by the C1q-binding assay) and with disease activity. C1q-binding activity and anti-DNA titers also correlated with disease activity. The correlations of C3, C4, CH50 and factor B with abnormal clearance and disease activity were weaker or nonexistent. The significant correlations among clearance, disease activity and C1q-binding activity suggest that the defect in Fc-receptor function may lead to the prolonged circulation of immune complexes, thereby contributing to tissue deposition and damage.