PMID- 16181211
OWN - NLM
STAT- MEDLINE
DCOM- 20051107
LR  - 20081121
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 45
IP  - 10
DP  - 2005 Oct
TI  - Characterization of immunoglobulin G fragments in liquid intravenous 
      immunoglobulin products.
PG  - 1601-9
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) products formulated as a liquid 
      instead of a powder have become commercially available. Preferably, such liquid 
      products should not alter after storage outside the refrigerator. Therefore, a 
      thorough characterization of immunoglobulin G (IgG) fragmentation at various 
      storage temperatures is required. STUDY DESIGN AND METHODS: Storage experiments 
      with liquid IVIG products from five manufacturers were performed at 4, 25, and 37 
      degrees C and IgG fragments were analyzed. RESULTS: Storage of liquid IVIG 
      products at 4 degrees C resulted in negligible alterations, whereas an increase 
      of IgG fragments was observed after prolonged storage at elevated temperatures. 
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot 
      analysis of five liquid IVIG products revealed three IgG fragments (12, 26, and 
      54 kDa) in all products. Fragments of similar molecular mass were produced upon 
      incubations of IgG with blood-derived proteases. N-terminal amino acid sequencing 
      revealed the cleavage site of these fragments, suggesting human neutrophil 
      elastase to cause the 12-kDa fragment. The presence of elastase in liquid IVIG 
      was confirmed by enzyme-linked immunosorbent assay. The origin of the 26- and 
      54-kDa fragments, both with an aspartic acid residue at the cleavage site, could 
      not be determined unambiguously. CONCLUSION: IgG fragmentation in liquid IVIG is 
      negligible when stored in the refrigerator. Only after prolonged storage at 
      elevated temperature does proteolytic degradation of IgG become apparent.
FAU - Diemel, Robert V
AU  - Diemel RV
AD  - Department of Immunopathology, Section of Immunoglobulin Research, Sanquin 
      Research at CLB, Amsterdam, the Netherlands.
FAU - ter Hart, Hendricus G J
AU  - ter Hart HG
FAU - Derksen, Gerardus J A
AU  - Derksen GJ
FAU - Koenderman, Anky H L
AU  - Koenderman AH
FAU - Aalberse, Rob C
AU  - Aalberse RC
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Immunoglobulin Fragments)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
SB  - IM
MH  - Blotting, Western
MH  - Chromatography, Liquid
MH  - Cold Temperature
MH  - Drug Storage
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Immunoglobulin Fragments/*analysis
MH  - Immunoglobulin G/*analysis/metabolism
MH  - Immunoglobulins, Intravenous/*chemistry
MH  - Leukocyte Elastase/analysis/metabolism
MH  - Molecular Weight
MH  - Peptide Hydrolases/metabolism
MH  - Refrigeration
MH  - Sequence Analysis, Protein
MH  - Temperature
EDAT- 2005/09/27 09:00
MHDA- 2005/11/08 09:00
CRDT- 2005/09/27 09:00
PHST- 2005/09/27 09:00 [pubmed]
PHST- 2005/11/08 09:00 [medline]
PHST- 2005/09/27 09:00 [entrez]
AID - TRF00549 [pii]
AID - 10.1111/j.1537-2995.2005.00549.x [doi]
PST - ppublish
SO  - Transfusion. 2005 Oct;45(10):1601-9. doi: 10.1111/j.1537-2995.2005.00549.x.