Immune Complex Disease in Experimental Animals and Man

Cochrane, Charles G.; Koffler, David

doi:10.1016/s0065-2776(08)60298-9

Cited by 517 publications

(168 citation statements)

References 266 publications

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“…With respect to the first possibility, immune complexes bearing fragments of C3 are present in patients with SLE (49), and these may interact with CR1 and CR2 to cause their removal from the cell surface, as has been demonstrated in vitro with receptor-specific antibodies (50,51). Secondary deficiencies of CR1 on erythrocytes have been shown to occur in SLE and in autoimmune hemolytic anemias in association with the generation of C3 cleavage fragments (6,7,52).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus

Wilson

Ratnoff

Schur

et al. 1986

Arthritis & Rheumatism

167

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Decreased numbers of complement receptor type 1 (CR1) have been observed on erythrocytes of patients wilh systemic lupus erythematosus (SLE) and on glomerular podocytes of patients having proliferative nephritis of SLE. In the present study, the analysis of the cellular expression of CR1 has been extended to include leukocytes. In addition, expression by B lymphocytes of the C3d receptor (CR2), which also serves as the receptor for the Epstein-Barr virus, was assessed. Receptor expression was measured by 2-color fluorescent flow cytometry of peripheral blood B cells, identified by the presence of the B1 antigen, that had also been stained with anti-CR1 or anti-CR2. B cells from 17 patients with SLE exhibited a mean relative fluorescence for CR1 that was 61% of that found in 17 normal individuals (P < 0.001). The expression of CR2 by the patients' B cells (n = 14) was 62% of that of the B cells fraim normal subjects (n = 17) (P < 0.001). The expression of CR1 correlated with that of CR2 among patients (r = 0.63; P < 0.01) but not with the expression of CR2 among normal individuals (r = 0.36; P > 0.1).Thle mean CR1 content of the patients' neutrophils was only 59% of the normal mean (P < 0.001). Thus, abnormalities of complement receptor expression occur

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Section: Discussionmentioning

confidence: 99%

Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus

Wilson

Ratnoff

Schur

et al. 1986

Arthritis & Rheumatism

167

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“…Various genetic and environmental factors, including B cell hyperactivity, T cell dysfunction, and cytokine dysregulation, initiate immune activation in SLE that culminates in organ inflammation and damage (1)(2)(3)(4)(5)(6)(7)(8)(9). It has been considered that B cells are innocent bystanders that are activated secondarily by autoreactive T lymphocytes.…”

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confidence: 99%

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

Otsuka

Horiuchi

Yoshizawa

et al. 2004

Arthritis & Rheumatism

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Objective. To investigate whether polymorphism(s) or mutation(s) in the hematopoietic cellspecific Lyn substrate 1 (HS1) gene are involved in the pathogenesis of systemic lupus erythematosus (SLE).Methods. The entire coding region of the HS1 gene was analyzed by reverse transcriptase-polymerase chain reaction/single-strand conformational polymorphism analysis. HS1-transfected WEHI-231 cells or B lymphocytes from patients with SLE were studied for apoptosis, activation, and proliferation by flow cytometric analysis and MTT assay.Results. We identified a glutamic acid-prolineglutamic acid-proline insertion between codons 366 and 367 (EPEP366-367ins) and 2 amino acid substitutions (A235T and E361K). The genotype frequency among individuals homozygous for the EPEP؉ allele was 0.184 in 201 patients with SLE but only 0.098 in 184 healthy individuals (P ‫؍‬ 0.016). The allele frequency of EPEP366-367ins was 0.408 in patients with SLE; this frequency was significantly higher than that in healthy controls (0.312) (P ‫؍‬ 0.006). WEHI-231 cells transfected with EPEP؉ HS1 were 100-fold more sensitive to B cell receptor (BCR)-mediated apoptosis than were those transfected with HS1 without EPEP. B lymphocytes from SLE patients with the EPEP؉ allele were significantly more apoptotic without BCR stimulation and less activated after BCR stimulation than were those from SLE patients without the EPEP allele. Conclusion. These results suggest that HS1 with the EPEP insertion polymorphism transmits accelerated signals from BCR and is involved in the pathogenesis of SLE.Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the presence of a variety of autoantibodies. Various genetic and environmental factors, including B cell hyperactivity, T cell dysfunction, and cytokine dysregulation, initiate immune activation in SLE that culminates in organ inflammation and damage (1-9). It has been considered that B cells are innocent bystanders that are activated secondarily by autoreactive T lymphocytes. However, recent evidence from the study of human SLE and its murine models suggests that B lymphocytes are intrinsically defective and are primarily essential for the maintenance of activated/memory T cells by presenting antigens to T cells.B cells from mice deficient in Lyn (10-12), CD22 (13-16), SHP-1 (17,18) exhibit a hyperreactive phenotype and produce autoantibodies. Indeed, Lyn-deficient mice demonstrate activation of autoreactive B cells and subsequent SLE-like symptoms, such as the production of anti-double-stranded DNA (anti-dsDNA)

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“…Circulating immune complexes are a characteristic feature of both human and murine systemic lupus erythematosus (9). Although many antibody systems have been identified in this disease, there is little information available so far regarding the nature of the antigen or antibody within the circulating immune complex.…”

Section: Discussionmentioning

confidence: 99%

Circulating c1q binding immune complexes in relatives of patients with systemic lupus erythematosus

Elkon

Walport

Rynes

et al. 1983

Arthritis & Rheumatism

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Immune Complex Disease in Experimental Animals and Man

Cited by 517 publications

References 266 publications

Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus

Decreased expression of the C3b/C4b receptor (CR1) and the C3d receptor (CR2) on B lymphocytes and of CR1 on neutrophils of patients with systemic lupus erythematosus

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

Circulating c1q binding immune complexes in relatives of patients with systemic lupus erythematosus

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