Defective Reticuloendothelial System Fc-Receptor Function in Systemic Lupus Erythematosus

Frank, Michael M.; Hamburger, Max I.; Lawley, Thomas J.; Kimberly, Robert P.; Plötz, Paul H.

doi:10.1056/nejm197903083001002

Cited by 478 publications

(144 citation statements)

References 17 publications

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“…It has been postulated that complement deficiency may predispose to the disease as a consequence of impairment of the processing of immune complexes, and there is direct experimental evidence, obtained from the study of immune complex processing in patients with SLE, that this is the case [12]. However, Fc receptors are also of major importance in immune complex processing, and there is evidence from the study of the clearance of IgG-opsonized erythrocytes in SLE patients that Fc-receptor function in SLE may be impaired [2]. These observations suggest that Fc R genes are good candidates for causing disease susceptibilty or disease modification.…”

Section: Discussionmentioning

confidence: 99%

FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease

Botto¹,

Theodoridis²,

Thompson

et al. 1996

Clinical and Experimental Immunology

109

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SUMMARYAn allotypic variant of Fc°RIIa, Fc°RIIa-HR (Fc°RIIa-R131), has been shown in vitro to reduce the capacity of phagocytic cells to bind and internalize IgG-containing immune complexes. Our aim was to determine whether this allotypic variant was associated with susceptibility to SLE and the development of lupus nephritis, as previous studies have suggested. Fc°RIIA genotype analysis was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 215 Caucasoid, 70 Afro-Caribbean, and 46 Chinese patients with SLE, and in 259, 77, and 49 ethnically matched controls, respectively. Distribution of Fc°RIIa genotypes between the patients and ethnically matched controls was not significantly different in the three populations studied. No association between the Fc°RIIa-HR allotype and nephritis was found. Our results suggest that the Fc°RIIa-HR allotype is not a major factor predisposing to the development of SLE, or to lupus nephritis.

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Section: Discussionmentioning

confidence: 99%

FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease

Botto¹,

Theodoridis²,

Thompson

et al. 1996

Clinical and Experimental Immunology

109

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“…This was based on 4 patients, however, without a defined selection process (3). A more recent study (12) reporting a positive correlation of Clq and a graded scale of disease activity was based on single point assessment in each patient, and details of clinical activity, including renal involvement, were not stated. Immune complex measurement in SLE by other assays have had variable results.…”

Section: Discussionmentioning

confidence: 99%

The C1q binding assay in systemic lupus erythematosus

Inman

Fong

Pussell

et al. 1980

Arthritis & Rheumatism

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To investigate the relationship of Clq binding assay (ClqBA) to disease activity in systemic lupus erythematosus (SLE), a retrospective study was carried out on 232 ClqBA performed in 33 patients with SLE.When initial values only were assessed (33 tests in 33 patients), there was no relationship between positive and negative ClqBA and abnormal renal function (P = 0.482, Fisher exact test). Of 87 tests performed during active renal disease, 34 (39%) were positive; of 48 tests during active non-renal disease, 25 (52%) were positive; of 83 tests when the disease was inactive, 45 (54%) were positive; and of 14 tests during episodes of infection, 10 (71%) were positive. Corresponding means for the ClqBA were as follows: renal 65.66, non-renal78.02, inactive 56.04, infection 135.79 (no significant diarerences by Student's f-test). There was no significant relationship with the ClqBA when comparing active disease (renal and non-renal) with inactive disease ($ Yates = 1.875, P = 0.171). When renal function abnormalities were analyzed separately, the ClqBA values were inde-

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“…Annealing temperatures were 55°C for Fc␥RI and GAPDH, 60°C for Fc␥RIIa and Fc␥RIIb, and 62°C for Fc␥RIII. The PCR reaction was stopped after 20,23,26,29,32,35,38,41, and 44 cycles at the very end of the extension phase (72°C), and 5-l samples were obtained.…”

Section: Methodsmentioning

confidence: 99%

“…The function of Fc␥RIIIb, which lacks an intracellular domain, is still unknown (18). Coordinate expression of Fc␥R has been implicated in various diseases involving ICs, such as diabetes (19), systemic lupus erythematosus (20,21), multiple sclerosis (22,23), autoimmune anemia (24,25), and RA (26).…”

mentioning

confidence: 99%

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

Blom¹,

Radstake²,

Holthuysen³

et al. 2003

Arthritis & Rheumatism

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Objective. To evaluate Fc␥ receptor (Fc␥R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor ␣ (TNF␣), interleukin-1␤ (IL-1␤), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc␥RI, Fc␥RII, and Fc␥RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation.Methods. Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc␥R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF␣, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc␥RI, Fc␥RII, and Fc␥RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/ collagenases was measured by degradation of fluorescent gelatin.Results. Immunohistochemistry showed higher Fc␥RII and Fc␥RIII expression in RA synovium than in controls. Fc␥RII and Fc␥RIII, but not Fc␥RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF␣ expression correlated positively with Fc␥RIII expression. Moreover, MMP-1 expression strongly correlated with Fc␥R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc␥RII and Fc␥RIII compared with controls. Twentyfour hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF␣ and gelatinase/collagenase was measured.Conclusion. RA synovium and mature RA macrophages express significantly elevated levels of Fc␥RII and Fc␥RIII, resulting in much higher production of TNF␣ and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc␥R on mature synovial macrophages is involved in the pathology of RA.

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Defective Reticuloendothelial System Fc-Receptor Function in Systemic Lupus Erythematosus

Cited by 478 publications

References 17 publications

FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease

FcγRIIa polymorphism in systemic lupus erythematosus (SLE): no association with disease

The C1q binding assay in systemic lupus erythematosus

Increased expression of Fcγ receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor α and matrix metalloproteinase

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