NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Effect of time, temperature and additives on a functional assay of C1 inhibitor.

Author(s): Nielsen EW, Johansen HT, Straume B, Mollnes TE

Publication: J Immunol Methods, 1994, Vol. 173, Page 245-51

PubMed ID: 8046257 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to determine the optimal conditions for blood specimen collection and storage when diagnosing hereditary angioedema (HAE) through measurement of the C1 inhibitor (C1-INH).

Conclusion of Paper

C1-INH activity was elevated in heparin treated plasma and depressed in polybrene-EDTA treated plasma. Significant declines in C1-INH levels were found in specimens stored at 4 degrees C and 37 degrees C. The decline in C1-INH activity with storage at either temperature was more pronounced in HAE patients than in normal patients. Storage of serum for 5 days at room temperature reduced C1-INH activity, but an observable effect on C1-INH levels by Western blot was only found in HAE patients. EDTA-treated plasma or serum were the best choices for measurement of C1-INH activity and while C1-INH activity levels declined with storage, HAE and normal specimens were still distinguishable after storage of serum for 5 days at room temperature.

Studies

  1. Study Purpose

    The purpose of this study was to determine the effects of anticoagulant and storage at 4 or 37 degrees C for up to 24 h on the activity of C1-INH in plasma and serum from normal and HAE patients. Serum specimens were allowed to coagulate for 2 h at room temperature prior to centrifugation. After the allotted storage time, all specimens were stored at -70 degrees C until analysis.

    Summary of Findings:

    C1-INH activity was falsely elevated in heparin treated plasma and falsely depressed in polybrene-EDTA treated plasma. Significantly higher C1-INH activity was observed in serum, EDTA-treated plasma and heparin-treated plasma, then in citrate-treated plasma from healthy volunteers (p=0.0003-0.0025), but not from HAE patients (p=0.055-0.8). Activity of C1-INH decreased by 12-19% after storage of normal plasma (EDTA, heparin, or citrate-treated) or serum for 24 h at 37 degrees C. A decline in C1-INH activity of 5-14% was noted after 24 h at 4 degrees C for normal plasma (EDTA, heparin, or citrate-treated) or serum. The decline in C1-INH activity was far more pronounced in HAE patients after storage at either 37 (48-83%) or 4 degrees C (35-80%) and was also found for polybrene-EDTA-treated plasma. Although a significant effect of storage was found for both healthy volunteers (p=0.039) and HAE patients (0.0002) there was no significant difference between the two temperatures. In conclusion, EDTA-treated plasma or serum were the best choices for measurement of C1-INH activity and C1-INH activity declines with storage at 4 or 37 degrees C.

    Biospecimens
    Preservative Types
    • Frozen
    Diagnoses:
    • Normal
    • Other diagnoses
    Platform:
    AnalyteTechnology Platform
    Protein Enzyme assay
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Preaquisition Diagnosis/ patient condition Hereditary angioedema
    Storage Storage temperature -70 degrees C
    4 degrees C
    37 degrees C
    Storage Storage conditions 0 h
    6 h
    24 h
    Biospecimen Acquisition Anticoagulant EDTA
    Heparin
    Sodium citrate
    Polybrene EDTA
    Biospecimen Aliquots and Components Blood and blood products Plasma
    Serum
  2. Study Purpose

    The purpose of this study was to determine the effect of storage of serum at room temperature for up to 5 days on the activity and protein levels of C1-INH from healthy volunteers and HAE patients. After the allotted storage time, all specimens were stored at -70 degrees C until analysis.

    Summary of Findings:

    Storage of pooled serum at room temperature decreased C1-INH activity levels by 15% after 1 day, 20% after 2 days, 24% after 3 days, and 22% after 5 days (p=0.055). While no changes in C1-INH levels in healthy individuals were observed by Western blot after 5 days of storage at room temperature, in HAE patients, the band representing intact C1-INH disappeared and a faint smaller band appeared after 5 days at room temperature. In addition, a new higher molecular weight band appeared both in serum from healthy volunteers and HAE patients. In conclusion, storage of serum at room temperature reduces C1-INH activity, but an observable effect on C1-INH levels by Western blot was only found in HAE patients.

    Biospecimens
    Preservative Types
    • Frozen
    Diagnoses:
    • Normal
    • Other diagnoses
    Platform:
    AnalyteTechnology Platform
    Protein Enzyme assay
    Protein Western blot
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Storage Time at room temperature 0 days
    1 day
    2 days
    3 days
    5 days
    Storage Storage temperature -70 degrees C
    Preaquisition Diagnosis/ patient condition Hereditary angioedema

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