Antibodies to calnexin and mutated calreticulin are common in human sera
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Antibodies to calnexin and mutated calreticulin are common in human sera. / Kyllesbech, Cecilie ; Trier, Nicole Hartwig; Mughal, Farah Perveen ; Hansen, Paul Robert; Holmström, Morten Orebo; el Fassi, Daniel; Hasselbalch, Hans; Skov, Vibe ; Kjær, Lasse ; Andersen, Mads Hald; Ciplys, Evaldas; Slibinskas, Rimantas ; Fredriksen, Jette Lautrup; Højrup, Peter; Houen, Gunnar .
I: Current Research in Translational Medicine, Bind 71, Nr. 2, 103380, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Antibodies to calnexin and mutated calreticulin are common in human sera
AU - Kyllesbech, Cecilie
AU - Trier, Nicole Hartwig
AU - Mughal, Farah Perveen
AU - Hansen, Paul Robert
AU - Holmström, Morten Orebo
AU - el Fassi, Daniel
AU - Hasselbalch, Hans
AU - Skov, Vibe
AU - Kjær, Lasse
AU - Andersen, Mads Hald
AU - Ciplys, Evaldas
AU - Slibinskas, Rimantas
AU - Fredriksen, Jette Lautrup
AU - Højrup, Peter
AU - Houen, Gunnar
PY - 2023
Y1 - 2023
N2 - Purpose of the studyCalreticulin is an endoplasmic reticulum chaperone protein, which is involved in protein folding and in peptide loading of major histocompatibility complex class I molecules together with its homolog calnexin. Mutated calreticulin is associated with a group of hemopoietic disorders, especially myeloproliferative neoplasms. Currently only the cellular immune response to mutated calreticulin has been described, although preliminary findings have indicated that antibodies to mutated calreticulin are not specific for myeloproliferative disorders. These findings have prompted us to characterize the humoral immune response to mutated calreticulin and its chaperone homologue calnexin.Patients and methodsWe analyzed sera from myeloproliferative neoplasm patients, healthy donors and relapsing-remitting multiple sclerosis patients for the occurrence of autoantibodies to wild type and mutated calreticulin forms and to calnexin by enzyme-linked immunosorbent assay.ResultsAntibodies to mutated calreticulin and calnexin were present at similar levels in serum samples of myeloproliferative neoplasm and multiple sclerosis patients as well as healthy donors. Moreover, a high correlation between antibodies to mutated calreticulin and calnexin was seen for all patient and control groups. Epitope binding studies indicated that cross-reactive antibodies bound to a three-dimensional epitope encompassing a short linear sequence in the C-terminal of mutated calreticulin and calnexin.ConclusionCollectively, these findings indicate that calreticulin mutations may be common and not necessarily lead to onset of myeloproliferative neoplasm, possibly due to elimination of cells with mutations. This, in turn, may suggest that additional molecular changes may be required for development of myeloproliferative neoplasm.
AB - Purpose of the studyCalreticulin is an endoplasmic reticulum chaperone protein, which is involved in protein folding and in peptide loading of major histocompatibility complex class I molecules together with its homolog calnexin. Mutated calreticulin is associated with a group of hemopoietic disorders, especially myeloproliferative neoplasms. Currently only the cellular immune response to mutated calreticulin has been described, although preliminary findings have indicated that antibodies to mutated calreticulin are not specific for myeloproliferative disorders. These findings have prompted us to characterize the humoral immune response to mutated calreticulin and its chaperone homologue calnexin.Patients and methodsWe analyzed sera from myeloproliferative neoplasm patients, healthy donors and relapsing-remitting multiple sclerosis patients for the occurrence of autoantibodies to wild type and mutated calreticulin forms and to calnexin by enzyme-linked immunosorbent assay.ResultsAntibodies to mutated calreticulin and calnexin were present at similar levels in serum samples of myeloproliferative neoplasm and multiple sclerosis patients as well as healthy donors. Moreover, a high correlation between antibodies to mutated calreticulin and calnexin was seen for all patient and control groups. Epitope binding studies indicated that cross-reactive antibodies bound to a three-dimensional epitope encompassing a short linear sequence in the C-terminal of mutated calreticulin and calnexin.ConclusionCollectively, these findings indicate that calreticulin mutations may be common and not necessarily lead to onset of myeloproliferative neoplasm, possibly due to elimination of cells with mutations. This, in turn, may suggest that additional molecular changes may be required for development of myeloproliferative neoplasm.
U2 - 10.1016/j.retram.2023.103380
DO - 10.1016/j.retram.2023.103380
M3 - Journal article
C2 - 36738659
VL - 71
JO - Current Research in Translational Medicine
JF - Current Research in Translational Medicine
SN - 2452-3186
IS - 2
M1 - 103380
ER -
ID: 333700710