Complement Diagnostics: Concepts, Indications, and Practical Guidelines

Nilsson, Bo; Ekdahl, Kristina Nilsson

doi:10.1155/2012/962702

Cited by 67 publications

(71 citation statements)

References 44 publications

(55 reference statements)

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“…We correlated eculizumab drug levels with the degree of complement blockade as measured by CH50. A normal CH50 level was 60 to 144 complement activity enzyme (CAE) units (ARUP Laboratories, Salt Lake City, UT) [32]. …”

Section: Methodsmentioning

confidence: 99%

Eculizumab Therapy in Children with Severe Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy

Jodele

Fukuda

Vinks

et al. 2014

Biology of Blood and Marrow Transplantation

212

225

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We recently observed that dysregulation of the complement system may be involved in the pathogenesis of hematopoietic stem cell transplantation–associated thrombotic microangiopathy (HSCT-TMA). These findings suggest that the complement inhibitor eculizumab could be a therapeutic option for this severe HSCT complication with high mortality. However, the efficacy of eculizumab in children with HSCT-TMA and its dosing requirements are not known. We treated 6 children with severe HSCT-TMA using eculizumab and adjusted the dose to achieve a therapeutic level >99 μg/mL. HSCT-TMA resolved over time in 4 of 6 children after achieving therapeutic eculizumab levels and complete complement blockade, as measured by low total hemolytic complement activity (CH50). To achieve therapeutic drug levels and a clinical response, children with HSCT-TMA required higher doses or more frequent eculizumab infusions than currently recommended for children with atypical hemolytic uremic syndrome. Two critically ill patients failed to reach therapeutic eculizumab levels, even after dose escalation, and subsequently died. Our data indicate that eculizumab may be a therapeutic option for HSCT-TMA, but HSCT patients appear to require higher medication dosing than recommended for other conditions. We also observed that a CH50 level ≤ 4 complement activity enzyme units correlated with therapeutic eculizumab levels and clinical response, and therefore CH50 may be useful to guide eculizumab dosing in HSCT patients as drug level monitoring is not readily available.

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Section: Methodsmentioning

confidence: 99%

Eculizumab Therapy in Children with Severe Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy

Jodele

Fukuda

Vinks

et al. 2014

Biology of Blood and Marrow Transplantation

212

225

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“…Compared to CB‐CAPs, soluble complement split products confer the advantage of shorter half‐lives and more rapid turnaround of the results. One such split product, iC3b, is the breakdown product of C3b (for a detailed outline, see Supplementary Figure 1, available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.40747/abstract) with a half‐life of ~90 minutes , compared to 2 minutes for C3a and C3b , and 50 hours for C3d . These properties offer the potential for employing iC3b to measure complement activation at the time of sampling.…”

Section: Introductionmentioning

confidence: 99%

Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity

Kim

Strand

Sen

et al. 2019

Arthritis & Rheumatology

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Objective To examine correlations between blood levels of complement split product iC 3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus ( SLE ). Methods A total of 159 consecutive patients with SLE , diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1–7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC 3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood iC 3b levels were measured by a lateral flow assay. SLE disease activity was monitored with the Responder Index 50 instrument of the SLE Disease Activity Index 2000. Results Relative changes in the iC 3b:C3 ratio, levels of anti–double‐stranded DNA (anti‐ds DNA ) antibodies, and use of a supraphysiologic dose of prednisone (>7.5 mg/day) each independently correlated with SLE disease activity, as determined in multilevel multiple logistic regression analyses. Only the iC 3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with SLE who were receiving a supraphysiologic dose of prednisone. The iC 3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active SLE from inactive SLE , and major flares from no disease activity. The iC 3:C3 ratio, anti‐ds DNA antibody levels, erythrocyte sedimentation rate, and use of a supraphysiologic prednisone dose were each independently associated with the presence of lupus nephritis, whereas none of these measures was associated with SLE rash. The association of the iC 3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations. Conclusion The ratio of blood iC 3b to serum C3 concentrations correlates with the extent of SLE disease activity and with clinically meaningful changes in disease activity in patients with SLE . Furthermore, the iC 3b:C3 ratio may discriminate between active and inactive...

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“…Compared to CB-CAPs, soluble complement split products confer the advantage of shorter half-lives and more rapid turnaround of the results. One such split product, iC3b, is the breakdown product of C3b (35) (for a detailed outline, see Supplementary Figure 1, available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/doi/10.1002/art.40747/abstract) with a half-life of ~90 minutes (36), compared to 2 minutes for C3a (37) and C3b (36), and 50 hours for C3d (38). These properties offer the potential for employing iC3b to measure complement activation at the time of sampling.…”

Section: Introductionmentioning

confidence: 99%

54 Blood concentrations of complement split product iC3b and serum C3 associate with systemic lupus erythematosus disease activity

Kim¹,

Strand

Sen³

et al. 2019

Abstracts

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Objective. To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE).Methods. A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CAS-TLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b to serum C3 concentrations. Serum C3 and C4 levels were measured by nephelometry, and blood iC3b levels were measured by a lateral flow assay. SLE disease activity was monitored with the Responder Index 50 instrument of the SLE Disease Activity Index 2000.Results. Relative changes in the iC3b:C3 ratio, levels of anti-double-stranded DNA (anti-dsDNA) antibodies, and use of a supraphysiologic dose of prednisone (>7.5 mg/day) each independently correlated with SLE disease activity, as determined in multilevel multiple logistic regression analyses. Only the iC3b:C3 ratio was significantly associated with clinically meaningful improvements in disease activity among patients with SLE who were receiving a supraphysiologic dose of prednisone. The iC3b:C3 ratio outperformed C3 and C4 levels with regard to discriminating active SLE from inactive SLE, and major flares from no disease activity. The iC3:C3 ratio, anti-dsDNA antibody levels, erythrocyte sedimentation rate, and use of a supraphysiologic prednisone dose were each independently associated with the presence of lupus nephritis, whereas none of these measures was associated with SLE rash. The association of the iC3b:C3 ratio with lupus nephritis was independent of other observed clinical manifestations.Conclusion. The ratio of blood iC3b to serum C3 concentrations correlates with the extent of SLE disease activity and with clinically meaningful changes in disease activity in patients with SLE. Furthermore, the iC3b:C3 ratio may discriminate between active and inactive SLE, and between major flares and no active disease.

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Complement Diagnostics: Concepts, Indications, and Practical Guidelines

Cited by 67 publications

References 44 publications

Eculizumab Therapy in Children with Severe Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy

Eculizumab Therapy in Children with Severe Hematopoietic Stem Cell Transplantation–Associated Thrombotic Microangiopathy

Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity

54 Blood concentrations of complement split product iC3b and serum C3 associate with systemic lupus erythematosus disease activity

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