Complement-regulatory protein expression and activation of complement cascade on erythrocytes from patients with rheumatoid arthritis (RA)

Arora, Meenakshi; Kumar, Ashok; Das, Srinibas; Srivastava, Lalit M.

doi:10.1046/j.1365-2249.1998.00449.x

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…Complement activation plays a pathogenic role in human RA, as suggested by the decreased levels of decay-accelerating factor (DAF) on the erythrocytes of RA patients (76), the activated phenotype of their polymorphonuclear cells (PMN) and monocytes (76)(77)(78), and the increased levels of complement regulatory proteins the DAF (CD55) and CR1 on PMN from RA synovial fluid (79). Among the several complement control proteins prepared by molecular biologic techniques, recombinant soluble CR1 has demonstrated the Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Dreja¹,

Annenkov

Chernajovsky

2000

Arthritis & Rheumatism

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Objective. The complement system is important in the development of autoimmune inflammation, including rheumatoid arthritis (RA) and collagen-induced arthritis (CIA). Complement receptor 1 (CR1) is involved in regulation of complement activity. Studies on models of autoimmunity have demonstrated that soluble CR1 (sCR1) is a potent therapeutic agent. The present study was thus undertaken to investigate the feasibility of antiinflammatory gene therapy to prevent CIA by delivery of genes encoding truncated sCR1 (tsCR1) and dimeric tsCR1-Ig.Methods. Syngeneic fibroblasts or arthritogenic splenocytes, engineered to express tsCR1 using retrovirus-mediated gene transfer, were injected into DBA/1 recipients that had been immunized with bovine type II collagen (CII). In separate experiments, naked DNA containing tsCR1 and tsCR1-Ig genes was injected intramuscularly into the immunized animals. The clinical development of arthritis was monitored, anti-CII levels measured, and antigenic T cell response studied. Affinity-purified tsCR1-Ig was assayed for its inhibitory effect on the alternative complement pathway in mouse serum.Results. Treatment of CII-immunized mice with the tsCR1-expressing cells inhibited development of CIA, reduced anti-CII antibody levels, and inhibited T cell response to CII in vitro. Intramuscular injections of DNA encoding the CR1 genes prevented the progression of disease. Furthermore, compared with full-length sCR1, purified tsCR1-Ig was more active in inhibiting the murine alternative complement pathway.Conclusion. Our findings demonstrated that tsCR1 and tsCR1-Ig, when delivered via gene therapy, had a beneficial effect on autoimmune inflammation. These results indicate that targeting the complement system in RA patients may be of clinical importance.

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Section: Discussionmentioning

confidence: 99%

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Dreja¹,

Annenkov

Chernajovsky

2000

Arthritis & Rheumatism

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“…These findings were reiterated in the passive K/BxN serum–transfer model (18, 19). The observation that CD55 is expressed at very high levels on fibroblast‐like synoviocytes (FLS) (20–23) has prompted speculation on its role in RA in connection with the complement system (24, 25).…”

mentioning

confidence: 99%

Deletion of either CD55 or CD97 ameliorates arthritis in mouse models

Hoek¹,

Launay²,

Kop³

et al. 2010

Arthritis & Rheumatism

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Objective. CD55 (decay-accelerating factor) is best known for its role in the negative regulation of the complement system. Indeed, lack of this molecule leads to disease aggravation in many autoimmune disease models. However, CD55 is abundantly present on fibroblast-like synoviocytes and is also a ligand of the adhesion-class heptahelical receptor CD97, which is expressed by infiltrating macrophages. Treatment with antibodies to CD97 ameliorates the collagen-induced model of rheumatoid arthritis (RA) in DBA/1 mice, but the net contribution of CD55 is unknown. This study was undertaken to investigate the role of CD55 in experimental RA.Methods. Arthritis was induced in wild-type, CD55 ؊/؊ , and CD97 ؊/؊ mice using collagen-induced and K/BxN serum-transfer models. Incidence of arthritis was monitored over time, and disease activity was assessed by clinical and immunohistochemical evaluation.Results. In contrast to observations in many inflammatory disease models, lack of CD55 resulted in decreased arthritis in experimental models of RA. Consistent with the previously reported effects of anti-CD97 antibody treatment, CD97 ؊/؊ mice had reduced arthritis activity compared with wild-type controls.Conclusion. Our findings indicate that the lack of CD55 or CD97 in 2 different models of arthritis increases resistance to the disease. These findings provide insight into a role for CD55 interaction with CD97 in the pathogenesis of RA and suggest that therapeutic strategies that disrupt CD55/CD97 may be clinically beneficial.

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“…This was doubted by the experimental evidence, since Arora et al observed no alteration in the expression of DAF and MIRL after incubating normal erythrocytes with RA patient sera whose RBCs exhibited significantly diminished expression of CD55 and CD59 [67]. In addition, the authors proposed as the cause, the spontaneous vesiculation that occurred to erythrocytes incubated with MAC, whose vesicles contained DAF, MIRL, and CR1[86,87].…”

Section: Discussionmentioning

confidence: 99%

“…Since 1981, when Miyakawa et al initially managed to demonstrate the diminished expression of Cregs, particularly that of CR1 (C3b receptor), on red-cell membrane of patients with SLE [ 79 ], several flow-cytometric and immunofluorescence studies have evaluated the presence of DAF and MIRL on erythrocytes in autoimmune diseases like SLE [ 59 , 60 , 63 – 65 ] and RA [ 67 , 68 ], without determining a specific pattern of the expression of these antigens. Primarily performed on a small sample of patients, they revealed a significant deficiency of these molecules – either jointly or separately – on RBCs, although without association with complement activity, the presence of anemia or antiphospholipid antibodies (aPLA) and clinical status [ 61 , 63 – 65 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

The presence of CD55- and/or CD59-deficient erythrocytic populations in patients with rheumatic diseases reflects an immune-mediated bone-marrow derived phenomenon

et al. 2014

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BackgroundComplement has the potential to provoke severe impairment to host tissues, as shown in autoimmune diseases where complement activation has been associated with diminished CD55 and/or CD59 expression on peripheral blood cell membranes. The aim of this study was to evaluate the presence of CD55- and/or CD59-deficient erythrocytic populations in patients with different rheumatic diseases and to investigate possible correlations with clinical or laboratory parameters.Material/MethodsCD55 and CD59 expression was evaluated in erythrocytes of 113 patients with rheumatic diseases, 121 normal individuals, and 10 patients with paroxysmal nocturnal hemoglobinuria (PNH) using the Sephacryl gel microtyping system. Ham and sucrose tests were also performed.ResultsInterestingly, the majority of patients (104/113, 92%) demonstrated CD55- and/or CD59-deficient erythrocytes: 47 (41.6%) with concomitant deficiency of CD55 and CD59, 50 (44.2%) with isolated deficiency of CD55, and 6 (6.2%) with isolated deficiency of CD59. In normal individuals, only 2 (1%) had concomitant CD55/CD59 negativity and 3 (2%) had isolated CD55 or CD59 deficiency. All PNH patients exhibited simultaneous CD55/CD59 deficiency. Positive Ham and sucrose tests were found only in PNH patients. There was no association between the CD55- and/or CD59-deficient erythrocytes and hemocytopenias or undergoing treatment. However, CD55 expression significantly influenced hemoglobin values (F=6.092, p=0.015).ConclusionsThis study provides evidence supporting the presence of erythrocytes with CD55 and/or CD59 deficiency in patients with rheumatic diseases. Moreover, CD55 deficiency on red cells influences hemoglobin concentration. Further studies using molecular techniques will clarify the exact pathophysiological mechanisms of this deficiency.

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Complement-regulatory protein expression and activation of complement cascade on erythrocytes from patients with rheumatoid arthritis (RA)

Cited by 12 publications

References 31 publications

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Soluble complement receptor 1 (CD35) delivered by retrovirally infected syngeneic cells or by naked DNA injection prevents the progression of collagen-induced arthritis

Deletion of either CD55 or CD97 ameliorates arthritis in mouse models

The presence of CD55- and/or CD59-deficient erythrocytic populations in patients with rheumatic diseases reflects an immune-mediated bone-marrow derived phenomenon

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