Factor B activation products in patients with systemic lupus erythematosus. A marker of severe disease activity

Kerr, Leslie Dubin; Adelsberg, Bernard R.; Schulman, Paul; Spiera, Harry

doi:10.1002/anr.1780321109

Cited by 33 publications

(16 citation statements)

References 16 publications

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“…Thus in LCV. as in SLE or RA [6][7][8][9][10], C3d,g and TCC appear to be sensitive indicators of systemic eomplement aetivation. Measurements of CH^o in plasma revealed a significant increase in (i5% of lhe patients.…”

Section: Discussionmentioning

confidence: 99%

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Dauchel

Joly

Delpech

et al. 1993

Clinical and Experimental Immunology

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SUMMARY We have studied complement activation both in plasma samples and In lesional skin from palients with leukocytoclaslic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers. C3d,g and fhe terminal complement complex (TCC) in plasma, showed lhal their levels were significantly increased in 66% and 55% of the patienis, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, Clq, C4and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were signifieantly eorrelated. Importantly, a signifieant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of peri vascular dermal deposits of C3d,g and TCC in lesional skin from 96 Mi and 80% respectively of the patients (n= 25). There was a significant eorrelation between the intensity of the deposits of bolh markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits, Immunofluorescence studies at the epidermal basemenl membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presenee of both C3d,g and clusterin‐associatcd TCC perivascular deposits suggests an intervention of a regulatory mechanism oflocal complement activation in LCV. Einally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV.

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Section: Discussionmentioning

confidence: 99%

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Dauchel

Joly

Delpech

et al. 1993

Clinical and Experimental Immunology

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“…Elevated mean Ba concentrations were measured in 22 of 28 (79%) patients with RA and in 12 of 15 (80%) patients with SLE [90], The mean Ba fragment concentrations in plasma samples obtained from patients with gram-negative bacteremia were significantly elevated as compared with normal control donors. However, plasma samples from patients with gram-positive bacteremia or RA did not show elevated Ba fragment levels in this study [97], Adelsberg and coworkers [98][99][100] have published a series of reports describing a quantitative procedure utilizing isoelectric focusing in agarose, followed by immunofixation, to identify the presence of factor B activation fragments in patient plasma sam ples. Ba activation fragments were detected in 15 of 51 (29%) EDTA plasma samples obtained from a cross-sectional population of SLE patients [98,99], 2 of 25 plasma sam ples obtained from seropositive RA patients [100], and 6 of 6 plasma samples obtained from hemodialysis patients [100].…”

Section: Factor B Activation Catabolism and Fragment Production In Hmentioning

confidence: 54%

“…However, plasma samples from patients with gram-positive bacteremia or RA did not show elevated Ba fragment levels in this study [97], Adelsberg and coworkers [98][99][100] have published a series of reports describing a quantitative procedure utilizing isoelectric focusing in agarose, followed by immunofixation, to identify the presence of factor B activation fragments in patient plasma sam ples. Ba activation fragments were detected in 15 of 51 (29%) EDTA plasma samples obtained from a cross-sectional population of SLE patients [98,99], 2 of 25 plasma sam ples obtained from seropositive RA patients [100], and 6 of 6 plasma samples obtained from hemodialysis patients [100]. Bb frag ments could not be identified in any of the patient plasma samples evaluated.…”

Section: Factor B Activation Catabolism and Fragment Production In Hmentioning

confidence: 54%

Ba and Bb Fragments of Factor B Activation: Fragment Production, Biological Activities, Neoepitope Expression and Quantitation in Clinical Samples

Kolb¹,

Morrow²,

Tamerius³

1989

Complement Inflamm

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Factor B is a centrally important component of the alternative complement pathway. Alternative pathway activation results in factor B cleavage and production of the amino-terminal Ba and the carboxyl-terminal Bb fragments which have molecular weights of approximately 30,000 and 63,000 daltons, respectively. Both Ba and Bb fragments have been reported to express a variety of biological activities in vitro. Thus, binding of Ba and Bb fragments to specific B lymphocyte surface receptors modulates proliferation of prestimulated B cells. In addition, the enzymatically active Bb fragment induces activation and spreading of human and murine macrophages and monocytes as well as regulates C5a des Arg chemotactic activity. The fractional catabolic rate and metabolism of factor B in vivo is similar to that of C3, C4 and C5 complement proteins, which are among the most metabol- ically active plasma proteins in the circulatory system. Factor B hyperconsumption and increased catabolism, concomitant with factor B fragment production, occurs in a wide variety of diseases, including gram-negative sepsis, autoimmune diseases and burns. Measurement of alternative pathway activation in vivo has been attempted utilized a number of different techniques to quantitate factor B fragments in biological fluids. However, the recent development of enzyme immunoassays (EIA) employing monoclonal antibodies (MoAbs) reactive with factor B fragment neoepitopes provides the best approach currently available for the quantitation of factor B activation fragments. Results obtained using these new MoAb-based EIAs have indicated that factor B fragment concentrations were elevated, as compared with normal donor levels, in EDTA plasma samples obtained from patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). Plasma concentrations of factor B fragments, especially Ba fragment levels, in these patients showed a positive correlation with disease activity scores. One of the highest disease activity correlations was obtained with Ba fragment measurements in SLE plasma samples. In fact, the results strongly suggested that quantitation of Ba fragment levels in SLE plasma samples more accurately reflected disease activity and was a more sensitive predictor of impending flare in these patients than any other test(s) currently available.

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“…Complement activation, notably of the alternative pathway, can occur during pregnancy in a patient with SLE and frequently accompanies a flare of disease. High circulating levels of Ba have been reported to predict poor outcome in nonpregnant lupus patients (15). Similar complement activation can be observed in individuals with preeclampsia, but is distinguished in these cases by the apparent ability to maintain synthesis.…”

Section: Discussionmentioning

confidence: 66%

Activation of the Alternative Complement Pathway Accompanies Disease Flares in Systemic Lupus Erythematosus During Pregnancy

Buyon

Tamerius

Ordorica

et al. 1992

Arthritis & Rheumatism

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Objective. To assess the activity of systemic lupus erythematosus (SLE) during pregnancy and to distinguish it from preeclampsia.Methods. We prospectively measured the complement activation products Ba, Bb, SC5b-9, and C4d, as well as the conventional complement determinants C3, C4, and CH50, during pregnancy in 14 patients with SLE and 10 women with preeclampsia.Results. Four of the 14 SLE patients were considered to have disease flares, 3 occurring in the second trimester and 1 postpartum. In these patients, significant abnormalities of Ba, Bb, SC5b-9, and CH50 were noted. In contrast, measures of C4d did not distinguish between pregnant patients who had flares and those whose SLE remained stable. Although decreased values of C3 were rarely seen in the patients with stable disease, normal values of C3 during lupus pregnancy were not reliably associated with stable disease. Three of Submitted for publication January 17, 1991; accepted in revised form August 12, 1991.10 non-SLE patients with preeclampsia had elevated levels of Ba; however, in each case, the CH50 level was close to or within the normal range. This was in sharp contrast to the findings observed in the 4 patients with active SLE, in whom high levels of plasma Ba were always associated with low CH50 values. Moreover, the ratio of CH50 to Ba was significantly lower in the patients with lupus flares than in the non-SLE patients with preeclampsia.Conclusion. While a decline in the C W O level alone could otherwise be attributed to decreased synthesis of complement components, these data demonstrate that ongoing activation of the alternative complement pathway can accompany disease flares in pregnant women with SLE.

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Factor B activation products in patients with systemic lupus erythematosus. A marker of severe disease activity

Cited by 33 publications

References 16 publications

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Local and systemic activationofthe whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers

Ba and Bb Fragments of Factor B Activation: Fragment Production, Biological Activities, Neoepitope Expression and Quantitation in Clinical Samples

Activation of the Alternative Complement Pathway Accompanies Disease Flares in Systemic Lupus Erythematosus During Pregnancy

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