Editing Calreticulin (section)

== Clinical significance ==

Calreticulin binds to [[antibody|antibodies]] in certain area of [[Lupus erythematosus|systemic lupus]] and [[Sjögren syndrome|Sjögren]] patients that contain [[Anti-SSA/Ro autoantibodies|anti-Ro/SSA antibodies]]. Systemic lupus erythematosus is associated with increased autoantibody titers against calreticulin, but calreticulin is not a Ro/SS-A antigen. Earlier papers referred to calreticulin as an Ro/SS-A antigen, but this was later disproven. Increased autoantibody titer against human calreticulin is found in infants with complete congenital heart block of both the [[Immunoglobulin G|IgG]] and [[IgM]] classes.<ref>{{cite web | title = Entrez Gene: CALR calreticulin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=811}}</ref>

In 2013, two groups detected calreticulin mutations in a majority of [[Janus kinase 2|JAK2]]-negative/[[thrombopoietin receptor|MPL]]-negative patients with [[essential thrombocythemia]] and [[myelofibrosis|primary myelofibrosis]], which makes ''CALR'' mutations the second most common in [[myeloproliferative disease|myeloproliferative neoplasms]]. All mutations (insertions or deletions) affected the last exon, generating a reading [[Frameshift mutation|frame shift]] of the resulting protein, that creates a novel terminal peptide and causes a loss of endoplasmic reticulum [[ER retention|KDEL retention signal]].<ref name="pmid24325359">{{cite journal | vauthors = Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorena I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O'Meara S, McLaren S, Bianchi M, Silber Y, Dimitropoulou D, Bloxham D, Mudie L, Maddison M, Robinson B, Keohane C, Maclean C, Hill K, Orchard K, Tauro S, Du MQ, Greaves M, Bowen D, Huntly BJ, Harrison CN, Cross NC, Ron D, Vannucchi AM, Papaemmanuil E, Campbell PJ, Green AR | title = Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2 | journal = The New England Journal of Medicine | volume = 369 | issue = 25 | pages = 2391–405 | date = Dec 2013 | pmid = 24325359 | pmc = 3966280 | doi = 10.1056/NEJMoa1312542 }}</ref><ref name="pmid24325356">{{cite journal | vauthors = Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant'Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schönegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R | title = Somatic mutations of calreticulin in myeloproliferative neoplasms | journal = The New England Journal of Medicine | volume = 369 | issue = 25 | pages = 2379–90 | date = Dec 2013 | pmid = 24325356 | doi = 10.1056/NEJMoa1311347 | doi-access = free }}</ref>